| 1. |
- Ljungberg, Ulla K, et al.
(författare)
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The interaction between different domains of staphylococcal protein A and human polyclonal IgG, IgA, IgM and F(ab')2: separation of affinity from specificity
- 1993
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Ingår i: Molecular Immunology. - 1872-9142. ; 30:14, s. 1279-1285
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Tidskriftsartikel (refereegranskat)abstract
- Binding properties of staphylococcal protein A (SpA) to different human immunoglobulins have been investigated. In this analysis, intact SpA as well as SpA-derived fragments containing one to five IgG-binding domains of different compositions, were used. The affinity binding constants of the different proteins to human polyclonal IgG, IgA, IgM and F(ab')2-fragments as well as their binding capacity to the immunoglobulin molecules were determined. The results show that although all the proteins bound to IgG, regardless of size or composition, the binding strength differed significantly. Proteins containing five domains have a stronger affinity for IgG than those containing one or two. There were no marked differences in binding strength between different domains. However, the binding ability to IgA and IgM showed a marked difference between the various SpA-derived proteins of different compositions. This discrepancy was correlated to differences in their relative binding properties to isolated F(ab')2-fragments of IgG. Hence, we conclude that the binding affinity is mainly affected by the number of domains, whereas the binding specificity is to a large extent determined by which domains are selected.
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| 2. |
- Abelev, Betty, et al.
(författare)
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Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
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Tidskriftsartikel (refereegranskat)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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| 3. |
- Abelev, Betty, et al.
(författare)
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Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
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Tidskriftsartikel (refereegranskat)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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| 4. |
- Abelev, Betty, et al.
(författare)
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Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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| 5. |
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| 6. |
- Alestig, Erik, 1973, et al.
(författare)
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Core mutations, IL28B polymorphisms and response to peginterferon/ribavirin treatment in Swedish patients with hepatitis C virus genotype 1 infection
- 2011
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Ingår i: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients infected with hepatitis C virus (HCV) genotype 1 respond poorly to standard treatment with 50% or less achieving sustained virologic response. Predicting outcome is essential and could help avoid unnecessary treatment and reduce health cost. Recently, an association of amino acid substitutions in the core region and treatment outcome was observed in Japanese patients. In the present study, the impact of these mutations on response kinetics and treatment outcome was explored in Caucasian patients. Methods: The core region of HCV pre-treatment samples obtained from 50 patients treated with peginterferon/ribavirin in a previous Swedish clinical trial with genotype 1 infection were sequenced. The alleles at rs12979860, a single nucleotide polymorphism (SNP), were assessed in order to identify any co-association with this strong response predictor. Results: No association between treatment response and substitutions of core residue 91 was found. In contrast, substitutions of core residue 70 were observed in 6/21 (29%) non-responders, but only in one of 29 responders (p = 0.03), and were more common in subgenotype 1b (R70Q in 6 of 13 strains) than in 1a (R70P in 1 of 37 strains, p = 0.004). The rs12979860 SNP upstream of the IL28B gene was overall the strongest response predictor (p = 0.0001). Core 70 substitutions were associated with poorer response kinetics in patients carrying the CT genotype at rs12979860. Conclusions: The results indicate that substitutions of core residue 70 are related to treatment response in Caucasian patients with HCV-1b infection, but are of less importance than IL28B polymorphism.
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| 7. |
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| 8. |
- Ariander, Annaclara, et al.
(författare)
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Ethical challenges causing moral distress: nursing home staff's experiences of working during the COVID-19 pandemic
- 2024
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Ingår i: Scandinavian Journal of Primary Health Care. - : TAYLOR & FRANCIS LTD. - 0281-3432 .- 1502-7724.
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo investigate the experiences of healthcare staff in nursing homes during the COVID-19 pandemic.DesignIndividual interviews. Latent qualitative content analysis.SettingTen nursing homes in Sweden.SubjectsPhysicians, nurses and nurse assistants working in Swedish nursing homes.Main outcome measuresParticipants' experiences of working in nursing homes during the COVID-19 pandemic.ResultsFour manifest categories were found, namely: Balancing restrictions and allocation of scarce resources with care needs; Prioritizing and acting against moral values in advance care planning; Distrust in cooperation and Leadership and staff turnover - a factor for moral distress. The latent theme Experiences of handling ethical challenges caused by the COVID-19 pandemic gave a deeper meaning to the categories.ConclusionDuring the pandemic, nursing home staff encountered ethical challenges that caused moral distress. Moral distress stemmed from not being given adequate conditions to perform their work properly, and thus not being able to give the residents adequate care. Another aspect of moral distress originated from feeling forced to act against their moral values when a course of action was considered to cause discomfort or harm to a resident. Alerting employers and policymakers to the harm and inequality experienced by staff and the difficulty in delivering appropriate care is essential. Making proposals for improvements and developing guidelines together with staff to recognize their role and to develop better guidance for good care is vital in order to support and sustain the nursing home workforce. The COVID-19 pandemic has affected both patients and staff in nursing homes, in Sweden and worldwide.Our study highlights that during the COVID-19 pandemic, nursing home staff encountered several ethical challenges which caused moral distress.Moral distress stemmed from not being given adequate conditions to perform their work, thus not giving the residents appropriate care.Moral distress could also originate from nursing home staff's feeling of being forced to act against their moral values.
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| 9. |
- Brodin, Yngve, et al.
(författare)
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Tvåvingar Diptera
- 2015
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Ingår i: Rödlistade arter i Sverige 2015. - 9789187853104 ; , s. 113-118
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Cederström, Peter, et al.
(författare)
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Fotblomflugor Platycheirus (Diptera, Syrphidae) längs den svenska fjällkedjan: en flerårig inventering.
- 2014
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Ingår i: Entomologisk tidskrift. - 0013-886X. ; 135, s. 109-130
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Tidskriftsartikel (refereegranskat)abstract
- The fauna of hoverflies in Boreal and Arctic parts of Scandinavia is still very poorly investigated. Therefore we performed an 11 year survey of the hoverfly genus Platycheirus Lepeletier & Serville, 1828 along the Caledonian mountain chain in Sweden (from Värmland northwards to the Torneträsk area). During 2003-2013 we annually performed two trips in order to survey various areas and to collect flies by netting. Altogether 150 localities were visited and a total of 1862 Platycheirus-specimens belonging to 40 species were collected. Two species were recorded for the first time in Sweden: Platycheirus carinatus(Curran, 1927) and P. magadanensis Mutin, 1999 and 74 records were new for various fauna-provinces. Four main areas were selected for comparative studies on distribution, habitat, local migration and environmental influences on population fluctuation of Platycheirus-species. We noted that males hatch earlier than females and the latter sex await the maturing anthers of their feeding plants. Moreover, Platycheirus-species in alpine and subalpine terrain seem to be very cold resistant and active at air-temperatures around 10O C. Environmental disturbance within the subalpine and northern boreal vegetation zones, e.g. cutting of woods or constructing of slalom slopes, creates new flower rich habitats and therefore support the population sizes within this assemblage of overflies. The observed distribution of northern Platycheirus-species along the Boreal and Arctic parts of Scandinavia reflects its worldwide Holarctic and Palearctic relations.
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| 11. |
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| 12. |
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| 13. |
- Ebenhard, Torbjörn, et al.
(författare)
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Environmental effects of brushwood harvesting for bioenergy
- 2017
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Ingår i: Forest Ecology and Management. - : Elsevier BV. - 0378-1127 .- 1872-7042. ; 383, s. 85-98
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Tidskriftsartikel (refereegranskat)abstract
- Sweden aims to increase the proportion of renewable energy sources, ultimately to be able to phase out fossil fuels. To achieve this, new energy sources need to be explored. In this multi-disciplinary article, we examine the technical, economical, ecological and legal possibilities to commercially and sustainably harvest brushwood for bioenergy, while simultaneously gaining positive environmental effects, both for biological diversity, the cultural heritage, and the climate. The Swedish open landscape is becoming covered with secondary brushwood regrowth through natural succession, except where it is kept open. Brushwood is spreading along roads, railway lines, edge zones, in power line corridors, abandoned semi-natural grasslands, nature reserves, and in marginal land in urban areas. Such brushwood consists of saplings, bushes and young trees of a range of deciduous plant species, e.g. birch, aspen, alder and goat willow, sometimes mixed with conifers, often forming dense thickets. Such secondary brushwood regrowth could be systematically utilised as a new source of renewable bioenergy. Commercial brushwood harvesting in Sweden may contribute 26 PJ of energy annually, which may be a small but significant contribution, considering the favourable energy ratio (E-r = 28), indicating that large emission reductions can be achieved, if fossil fuels are replaced. Growing brushwood does not require fertilizers or pesticides, soil tillage or crop management, and it does not compete with any other potential land use. Many brushwood habitats are already being managed to clear brushwood, for other purposes, minimizing the added harvesting cost. Apart from providing bioenergy, it has also been suggested that brushwood harvesting would benefit biological diversity. A large number of nationally redlisted species are dependent on the active management of open habitats, including semi-natural grasslands, and man-made habitats such as road verges and power line corridors. Our literature review shows that brushwood harvesting could benefit both biological diversity and the cultural heritage, and contribute to the management of the open cultural landscape. There are however certain limitations. Brushwood harvesting would favour a certain set of species, including many redlisted, but it may also threaten another set of species, especially species associated with early successional stages of forest regeneration, as well as forest edge species, depending on how and where it is applied. Harvesting may be affected by legislation imposing limitations regarding habitats of particular importance for biodiversity. The environmental and legal constraints would probably reduce the profitability of brushwood harvesting in certain areas, as well as the annual production of bioenergy.
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| 14. |
- 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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| 15. |
- Elgström, Erika, et al.
(författare)
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Change in Cell Death Markers During (177)Lu-mAb Radioimmunotherapy-Induced Rejection of Syngeneic Rat Colon Carcinoma.
- 2014
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Ingår i: Cancer Biotherapy & Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1557-8852 .- 1084-9785. ; 29:4, s. 143-152
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Purpose: To monitor cell death in tumors during the rejection process after treatment with an antibody radiolabeled with a β-emitter. Methods: Tumors during rejection after treatment with (177)Lu-labeled antibody BR96 and after administration of unlabeled BR96 were compared with untreated tumors from the same immunocompetent syngeneic rat tumor model. Cell death was monitored with the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and immunohistochemical staining of activated caspase-3 and γH2AX. These data were evaluated together with histopathological morphology, BR96-binding antigen expression, and (177)Lu radioactivity distribution imaged by digital autoradiography. Results: The untreated tumors showed staining for all the markers, mainly in and around the necrotic areas. One to 2 days p.i. large areas were stained with anti-γH2AX, followed by a slight decrease. Staining of activated caspase-3 was intense and extensive 1-2 days p.i., while found in and around necrotic areas 3-8 days p.i. TUNEL staining was similar to activated caspase-3 staining 1-2 days p.i. but more extensive than activated caspase-3 staining 3-4 days p.i. Digital autoradiography revealed activity concentration in granulation tissue from 1 day p.i. Conclusion: Following radioimmunotherapy in an immunocompetent syngeneic colon carcinoma model, tumor cells did not only die through caspase-3-dependent apoptosis, but also by other mechanisms.
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| 16. |
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| 17. |
- Elgström, Erika, et al.
(författare)
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Pattern of antigen expression in metastases after radioimmunotherapy of a syngeneic rat colon carcinoma utilizing the BR96 antibody.
- 2012
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Ingår i: Experimental hematology & oncology. - : Springer Science and Business Media LLC. - 2162-3619. ; 1:1
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Tidskriftsartikel (refereegranskat)abstract
- Abstract ABSTRACT: BACKGROUND: Repeated administration of antibody-based therapies such as radioimmunotherapy depends on preserved antigen expression in tumor lesions. The purpose of this study was to evaluate whether the antigen expression in metastases observed after radioimmunotherapy differs from that of untreated primary tumors. FINDINGS: 30 of the 35 Brown Norway rats with syngeneic colon carcinoma treated with 400 MBq/kg 177Lu-DOTA-BR96 exhibited consistent complete response of the primary tumor. 13 animals developed metastases that were detected after treatment. The antigen expression was reduced in 17 of 23 metastases detected after radioimmunotherapy compared with untreated tumors. No tumors completely lacked positively stained tumor cells. CONCLUSIONS: Although it was not possible to demonstrate that the antigen reduction is triggered by the radioimmunotherapy this result stress the importance of considering the risk of reduced antigen expression in metastases after radioimmunotherapy prior to further targeted therapies.
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| 18. |
- Elgström, Erika, et al.
(författare)
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Role of CD8-positive cells in radioimmunotherapy utilizing (177)Lu-mAbs in an immunocompetent rat colon carcinoma model.
- 2015
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Ingår i: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- CD8-positive cells might play a crucial role in the therapeutic response to radiation, which has however not been investigated in radioimmunotherapy (RIT). The aim of this study was to evaluate whether cytotoxic T cells affect the response of established tumors and, above all, if they delay or prevent the development of distant metastases after RIT, using an immunocompetent syngeneic rat colon carcinoma model.
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| 19. |
- Eriksson, Sophie, et al.
(författare)
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Repeated Radioimmunotherapy with (177)Lu-DOTA-BR96 in a Syngeneic Rat Colon Carcinoma Model.
- 2012
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Ingår i: Cancer Biotherapy & Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1557-8852 .- 1084-9785. ; 27:2, s. 134-140
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Aim: Fractionation is generally used as a mean to improve radioimmunotherapy (RIT). Since RIT is considered suitable for small-volume disease, the aim of the current study was to investigate whether repeated administration of (177)Lu-labeled mAb BR96 was tolerated and could delay or prevent metastatic disease after complete remission of the tumor obtained by the first administration. Methods: Immunocompetent rats bearing a syngeneic colon carcinoma were first treated with 400 MBq/kg (177)Lu-DOTA-BR96, an activity resulting in complete response in 29 of 30 animals. On day 21, two groups of rats were given an additional activity of 150 or 350 MBq/kg resulting in total administered activities corresponding to 0.9 and 1.3 times the maximal tolerated dose. Results: The additional treatment resulted in tolerable myelotoxicity; however, the frequency of metastatic disease and survival were not affected. Immunohistochemistry demonstrated binding of the BR96 antibody to tissue sections of analyzed metastases. Conclusions: In our model, development of metastatic disease after treatment of the manifest tumor was not prevented by an additional treatment with the same radioimmunoconjugate. Therefore, the antibody should be labeled with a more suitable radionuclide for treatment of metastases. The repeated targeted therapy was well tolerated in aspects of myelotoxicity.
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| 20. |
- Eriksson, Sophie, et al.
(författare)
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Sequential Radioimmunotherapy with (177)Lu- and (211)At-Labeled Monoclonal Antibody BR96 in a Syngeneic Rat Colon Carcinoma Model.
- 2014
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Ingår i: Cancer biotherapy & radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1557-8852 .- 1084-9785. ; 29:6, s. 238-246
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Alpha-particle emitters, such as astatine-211 ((211)At), are generally considered suitable for the treatment of small cell clusters due to their short path length, while beta-particle emitters, for example, Lutetium-177 ((177)Lu), have a longer path length and are considered better for small, established tumors. A combination of such radionuclides may be successful in regimens of radioimmunotherapy. In this study, rats were treated by sequential administration of first a (177)Lu-labeled antibody, followed by a (211)At-labeled antibody 25 days later. Methods: Rats bearing solid colon carcinoma tumors were treated with 400MBq/kg body weight (177)Lu-BR96. After 25 days, three groups of animals were given either 5 or 10MBq/kg body weight of (211)At-BR96 simultaneously with or without a blocking agent reducing halogen uptake in normal tissues. Control animals were not given any (211)At-BR96. Myelotoxicity, body weight, tumor size, and development of metastases were monitored for 120 days. Results: Tumors were undetectable in 90% of the animals on day 25, independent of treatment. Additional treatment with (211)At-labeled antibodies did not reduce the proportion of animals developing metastases. The rats suffered from reversible myelotoxicity after treatment. Conclusions: Sequential administration of (177)Lu-BR96 and (211)At-BR96 resulted in tolerable toxicity providing halogen blocking but did not enhance the therapeutic effect.
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| 21. |
- Eriksson, Sophie, et al.
(författare)
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Successful radioimmunotherapy of established syngeneic rat colon carcinoma with 211At-mAb.
- 2013
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Ingår i: EJNMMI research. - 2191-219X. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Most carcinomas are prone to metastasize despite successful treatment of the primary tumor. One way to address this clinical challenge may be targeted therapy with alpha-emitting radionuclides such as astatine-211 (211At). Radioimmunotherapy utilizing alpha-particle emitting radionuclides is considered especially suitable for the treatment of small cell clusters and single cells, although lesions of different sizes may also be present in the patient. The aim of this study was primarily to evaluate the toxicity and secondarily in vivo efficacy of a 211At-labeled monoclonal antibody (mAb) directed against colon carcinoma with tumor diameters of approximately 10 mm. METHODS: Eighteen rats with subperitoneal syngeneic colon carcinoma were allocated to three groups of six animals together with three healthy rats in each group. The groups were injected intravenously with either 150 mug of unlabeled mAbs (controls) or 2.5 or 5 MBq 211At-mAbs directed towards the Lewis Y antigen expressed on the cell membrane of several carcinomas. Tumor volume, body weight, and blood cell counts were monitored for 100 days after treatment. RESULTS: Local tumors were non-palpable in five out of six rats after treatment with both activities of 211At-mAbs, compared to one out of six in the control group. At the study end, half of the animals in each group given 211At-BR96 and one animal in the control group were free from disease. Radioimmunotherapy resulted in dose-dependent, transient weight loss and myelotoxicity. Survival was significantly better in the groups receiving targeted alpha therapy than in those receiving unlabeled mAbs. CONCLUSIONS: This study demonstrates the possibility of treating small, solid colon carcinoma tumors with alpha-emitting radionuclides such as 211At bound to mAbs, with tolerable toxicity.
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| 22. |
- Eriksson, Sophie, et al.
(författare)
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Treatment with Unlabeled mAb BR96 After Radioimmunotherapy with (177)Lu-DOTA-BR96 in a Syngeneic Rat Colon Carcinoma Model.
- 2012
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Ingår i: Cancer Biotherapy & Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1557-8852 .- 1084-9785. ; 27:3, s. 175-182
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Tidskriftsartikel (refereegranskat)abstract
- Metastatic disease after successful treatment of the primary tumor continues to be a therapeutic challenge. Enhancement of therapeutic effects by the administration of unlabeled monoclonal antibodies (mAbs) after radioimmunotherapy (RIT) may provide a means of preventing or delaying the development of metastatic disease. In the present study, Brown Norway rats with syngeneic grafted colon carcinomas were administered the minimal effective therapeutic dose of 400 MBq/kg lutetium-177 ((177)Lu)-DOTA-BR96. After 2 weeks, half of the animals were given 15 mg/kg unlabeled mAb BR96 as consolidation therapy. Treatment response and toxicity were monitored 100 days after the treatment with unlabeled BR96. The treatment with unlabeled mAb after RIT resulted in a complete response (CR) in 19 of 19 animals, while RIT alone resulted in a CR in 17 of 19 animals. The additional treatment did not affect the number of animals with metastatic disease or the time to clinical symptoms of metastases. RIT resulted in reversible myelotoxicity. The unlabeled mAb BR96 did not cause any additional toxicity, making it possible to repeat the consolidation therapy.
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| 23. |
- Garkavij, Michael, et al.
(författare)
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Enhanced radioimmunotargeting of 125I-labeled L6-biotin monoclonal antibody (MAb) by combining preload of cold L6 MAb and subsequent immunoadsorption in rats
- 1995
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Ingår i: Cancer Research. - 1538-7445. ; 55:23 Suppl, s. 5874-5880
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Tidskriftsartikel (refereegranskat)abstract
- The present study investigates whether tumor:normal tissue uptake ratios of radiolabeled monoclonal antibodies can be further improved by a combination of extracorporeal immunoadsorption (ECIA) and preload with unlabeled idiotypic monoclonal antibody. Athymic rats, heterotransplanted with human lung carcinoma under the kidney capsule (SR tumor) and i.m. (IM tumor), were divided into four study groups: controls, ECIA, preload, and combined preload+ECIA. The preload+ECIA procedure reduced the whole-body and plasma activity by 48 and 89%, respectively. After such combined procedure, the uptake of 125I-labeled L6-biotin in SR tumors was unchanged, while the uptake in normal tissues was considerably reduced. Tumor (T):bone marrow ratio was then increased by 17.5 times (after ECIA) and by 4.5 times (24 h after ECIA). Similar enhancements were achieved for T:liver and T:kidney ratios. For the IM tumors, the ratios were not as high as for SR tumors. The effects on T:normal ratios of preload+ECIA in combination were synergistic. The combined procedure resulted both in an increased uptake and prolonged persistence of 125I-labeled L6-biotin in the SR tumors and also in a reduction of corresponding uptake values in organs critical for radiation.
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| 24. |
- Garkavij, Michael, et al.
(författare)
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Extracorporeal immunoadsorption from whole blood based on the avidin-biotin concept. Evaluation of a new method
- 1996
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 35:3, s. 309-312
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Tidskriftsartikel (refereegranskat)abstract
- This study of 36 rats with rat colon adenocarcinoma transplants was carried out to investigate the efficacy of a new method of whole blood immunoadsorption (WBIA) in removing biotinylated monoclonal antibodies (MAbs) directly from unseparated blood, in order to increase 'the tumor/normal-tissue uptake ratio', as compared with extracorporeal immunoadsorption (ECIA) of antibodies from plasma. Compared with the ECIA system, the overall volume of the WBIA system (comprising only a pump, an adsorption column, a drop-chamber and tubings) was less (3.6 vs. 6.2 ml), and procedure duration 2 h less. The 17 rats undergoing the WBIA procedure, started 12 h after i.v. injection of 4.0-4.5 MBq 125I-BR96-biotin, manifested neither hemolysis nor any other complication; no signs of organ edema were found at dissection; whole body and blood radioactivity values were reduced by 51% and 89.5%, respectively. The WBIA method was as effective as ECIA, but technically simpler, safer and more reliable.
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| 25. |
- Garkavij, Martin, et al.
(författare)
-
Extracorporeal whole-blood immunoadsorption enhances radioimmunotargeting of iodine-125-labeled BR96-biotin monoclonal antibody
- 1997
-
Ingår i: Journal of Nuclear Medicine. - 0161-5505. ; 38:6, s. 895-901
-
Tidskriftsartikel (refereegranskat)abstract
- This study investigates the efficacy of tumor radioimmunotargeting with 125I-labeled BR96-biotin monoclonal antibody using a new method, whole-blood immunoadsorption (WBIA), based on direct adsorption of unbound monoclonal antibody (MAb) from blood without preceding separation of plasma. METHODS: Highly tumor-reactive, internalizing, chimeric BR96 MAb of isotype IgG1 binds to a tumor-associated Lewis-type (Le(Y)) cell surface antigen. Forty-six Brown Norwegian male rats were inoculated intramuscularly and beneath the liver or kidney capsule with syngeneic rat colon carcinoma BN7005, expressing Lewis-type antigen, and investigated. The rats were injected intravenously with 3.5-4.5 MBq 125I-labeled BR96-biotin. Twenty of the rats underwent WBIA starting 5 or 12 hr after injection. About six blood volumes were passed through an avidin-gel adsorption column during 2 hr. RESULTS: By using WBIA, whole-body radioactivity was reduced by 50%, and plasma activity by 85%. Both directly after completion of WBIA and 33 hr later, the activity uptake in tumors manifested only a nonsignificant decrease as compared with corresponding controls (p > 0.05) and had approximately similar time-activity curves. Uptake ratios for tumor (T):bone marrow, T:liver, T:kidney and T:lung were enhanced 2.3- to 3.5-fold in all three tumor models, as compared with controls. The ratio of liver tumor to bone marrow was improved from 10:1 to 30:1. CONCLUSION: This new method of WBIA yields significantly improved radioimmunotargeting of highly tumor-reactive, internalizing MAb BR96.
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| 26. |
- Garkavij, Michael, et al.
(författare)
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Improving radioimmonotargeting of tumors. Variation in the amount of L6 MAb administered, combined with an immunoadsorption system (ECIA)
- 1993
-
Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 32:7-8, s. 853-859
-
Tidskriftsartikel (refereegranskat)abstract
- Extracorporeal immunoadsorption (ECIA) is a new method for the selective removal of circulating radiolabeled monoclonal antibodies (MAb) from plasma to increase the uptake in tumor versus normal tissues (T/N-ratio). To ascertain whether the amount of MAb affects T/N ratios immediately and 24 h after ECIA, we used a rat model with two tumor sites--one intramuscular (im) and one below the subrenal capsule (SR). Extracorporeal immunoadsorption was done with an avidin-agarose column after injection of 125I-labeled biotinylated L6 MAb. The animals received 10, 50 or 250 micrograms of L6 only (controls), or followed by ECIA. The efficacy of the procedure in removing plasma activity was 80-95%. For both tumor sites, the highest T/N-ratios were obtained with 10 micrograms L6. All T/N-ratios significantly improved for SR tumors by a factor ranging from 3.2 (lung) to 12.6 (bone marrow). The T/N-ratios were still elevated 24 h after ECIA. Injection of larger amounts of MAb, probably causing a higher degree of tumor saturation, will not necessarily improve the T/N ratio after ECIA.
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| 27. |
- Garkavij, Michael, et al.
(författare)
-
Improving radioimmunotargeting of tumors: the impact of preloading unlabeled L6 monoclonal antibody on the biodistribution of 125I-L6 in rats
- 1994
-
Ingår i: Journal of nuclear biology and medicine (Turin, Italy : 1991). - 0368-3249. ; 38:4, s. 594-600
-
Tidskriftsartikel (refereegranskat)abstract
- In the radioimmunotherapy of malignancies the uptake of monoclonal antibodies (MoAb) is commonly low in tumors compared with normal tissue. Several methods have been suggested to increase the tumor-to-normal tissue (T/N) ratio. In this study we have investigated the biodistribution of different amounts of 125I-L6-biotin MoAb in combination with a preload of unlabeled L6 MoAb. Nude rats were injected with 50 micrograms or 250 micrograms of unlabeled L6 24 hours prior to the injection of 10 micrograms, 50 micrograms or 250 micrograms of 125I-L6, antipancarcinoma MoAb. Dissections were performed 24 hours after the injection of radiolabeled MoAb. The maximal enhancement of tumor uptake with simultaneously decreased uptake in normal tissues was with 250 micrograms of 125I-L6 preceded by a preload of 50 micrograms unlabeled L6. Mean T/N ratios were improved by a factor of 2.9 for bone marrow, 3.4 for liver, 3.7 for lungs and 2.3 for kidneys as compared with the corresponding controls. This study demonstrated that preinjection of optimal amounts of unlabeled L6 MoAb may increase the uptake of 125I-L6 by tumor and improve the T/N ratios. Based on present data, preloading with unlabeled MoAb should be considered in future clinical studies with immunoconjugates to improve the radioimmunotargeting of tumors. It is essential to titrate an appropriate amount of the preload, thus avoiding possible tumor antigen saturation of unlabeled MoAbs but simultaneously decreasing the uptake of subsequently injected radiolabeled MoAb in normal tissues.
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| 28. |
- Grillitsch, Markus, et al.
(författare)
-
Agency and economic change in regions : identifying routes to new path development using qualitative comparative analysis
- 2023
-
Ingår i: Regional Studies. - : Informa UK Limited. - 0034-3404 .- 1360-0591. ; 57:8, s. 453-1468
-
Tidskriftsartikel (refereegranskat)abstract
- This paper investigates the role of human agency in 40 phases of regional economic development in 12 Nordic regions over 30 years. It contributes with a theoretical framework to study agency over time and a fuzzy-set qualitative comparative analysis based on a unique dataset combining over 200 interviews, with printed and online sources, and quantitative data. The paper identifies which combinations of agency types and context conditions make industrial upgrading or diversification possible, and investigates how such combinations come into being. The causal claims from this analysis are illustrated with empirical examples and discussed in relation to previous literature.
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| 29. |
- Gustafsson, Erik, et al.
(författare)
-
Invasive Staphylococcus aureus strains are highly variable in PFGE patterns, agr group and exoprotein production
- 2009
-
Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa Healthcare. - 0036-5548 .- 1651-1980. ; 41:8, s. 577-583
-
Tidskriftsartikel (refereegranskat)abstract
- In the present study, we have investigated 37 invasive Staphylococcus aureus strains (collected between 1997 and 2005) from 33 human episodes of septicaemia causing either endocarditis or vertebral osteomyelitis. All S. aureus strains were typed using pulsed field gel electrophoresis (PFGE), and most strains belonged to any of 4 different PFGE clusters. There was no correlation between any of the PFGE clusters with site of infection. All strains showed highly different expression patterns of extracellular proteins, i.e. we found a vast variation in the number of proteins and amount of individual proteins expressed by the different strains. There was no correlation between any cluster of exoprotein patterns with endocarditis or with vertebral osteomyelitis. We did not find any correlation between agr group and endocarditis, as previously reported. On the other hand, a correlation between some of the PFGE clusters with a certain agr group was found. Known risk factors for S. aureus infections were observed in a majority of the patients.
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| 30. |
- Kurkus, Jan, et al.
(författare)
-
Biocompatibility of a novel avidin-agarose adsorbent for extracorporeal removal of redundant radiopharmaceutical from the blood.
- 2007
-
Ingår i: Artificial Organs. - : Wiley. - 0160-564X .- 1525-1594. ; 31:3, s. 208-214
-
Tidskriftsartikel (refereegranskat)abstract
- The use of monoclonal antibodies (MAbs) in cytotoxic conjugates (radionuclides, toxins, or drugs) for targeting tumor cells is restricted due to toxicity in vital organs. Through improved tumor targeting, it is possible to administer larger amounts of such labeled MAbs, thus improving the ability to eradicate tumor cells without increased normal organ toxicity. Extracorporeal affinity adsorption treatment (ECAT) has therefore been developed using an avidin-agarose (AA) adsorbent with high binding affinity for the biotinylated radiolabeled MAb, rituximab. During ECAT, excess radioimmunoconjugates, not bound to the tumor cells, can be removed improving tumor targeting. The present study was performed to estimate the biocompatibility of the AA adsorber. Seven patients with B-cell lymphoma not responding to conventional treatment were studied. During the ECAT procedure, blood (B) components, plasma (P) complement fragments C3a, C5a, and P-bradykinin were analyzed, and other laboratory tests were carried out. Slight decreases in B-hemoglobin (8.3%), B-thrombocytes (11.4%), and P-albumin (14.3%) were observed, and could be explained by the dilution of the blood with normal saline and acid citrate dextrose. The AA adsorbent had no effect on the blood cells, immunological status or P-bradykinin level. The AA adsorber demonstrated good hemocompatibility and biocompatibility, without any side effects in the patients.
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| 31. |
- Kvint, Sven, et al.
(författare)
-
Autotransplantation of teeth in 215 patients : A Follow-up Study
- 2010
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Ingår i: Angle orthodontist. - : The Angle Orthodontist (EH Angle Education & Research Foundation). - 0003-3219 .- 1945-7103. ; 80:3, s. 446-451
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the success rate of autotransplantation of teeth in consecutive patients and to analyze factors affecting the outcome. Materials andMETHODS: The subjects consisted of 215 consecutive patients (101 women and 114 men; aged 9.1-56.4 years, median age 15.2 years [P(10) = 11.4, P(90) = 19.7]) who had undergone transplantation of a total of 269 teeth, all by the same surgeon. In patients with multiple transplants, only the first transplant was included, to ensure that all transplanted teeth were independent units. The transplants were recorded as unsuccessful if the tooth had been extracted or was surviving but with root resorption or ankylosis. The interval between transplantation and final follow-up was a median 4.8 years (P(10) = 2.0, P(90) = 5.5) for successful transplants and a median of 2.4 years (P(10) = 0.4, P(90) = 7.7) for unsuccessful transplants.RESULTS: One-hundred seventy-five (81%) of the transplantations were recorded as successful and 40 (19%) as unsuccessful. Twenty-five teeth had been extracted and 15 had survived but did not fulfill the criteria for success.CONCLUSIONS: The success rate of 215 consecutively transplanted teeth was 81%. The highest success rate was for transplantation of premolars to the maxillary incisor region (100%). Complications at surgery such as difficult extraction, deviant root anatomy, or damaged root periodontium affected the outcome. During growth, a successful transplant preserves alveolar bone.
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| 32. |
- Larsson, Erik, et al.
(författare)
-
Use of Monte Carlo simulations with a realistic rat phantom for examining the correlation between hematopoietic system response and red marrow absorbed dose in Brown Norway rats undergoing radionuclide therapy with (177)Lu- and (90)Y-BR96 mAbs.
- 2012
-
Ingår i: Medical Physics. - : Wiley. - 0094-2405. ; 39:7, s. 4434-4443
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Biokinetic and dosimetry studies in laboratory animals often precede clinical radionuclide therapies in humans. A reliable evaluation of therapeutic efficacy is essential and should be based on accurate dosimetry data from a realistic dosimetry model. The aim of this study was to develop an anatomically realistic dosimetry model for Brown Norway rats to calculate S factors for use in evaluating correlations between absorbed dose and biological effects in a preclinical therapy study. Methods: A realistic rat phantom (Roby) was used, which has some flexibility that allows for a redefinition of organ sizes. The phantom was modified to represent the anatomic geometry of a Brown Norway rat, which was used for Monte Carlo calculations of S factors. Kinetic data for radiolabeled BR96 monoclonal antibodies were used to calculate the absorbed dose. Biological data were gathered from an activity escalation study with (90)Y- and (177)Lu-labeled BR96 monoclonal antibodies, in which blood cell counts and bodyweight were examined up to 2 months follow-up after injection. Reductions in white blood cell and platelet counts and declines in bodyweight were quantified by four methods and compared to the calculated absorbed dose to the bone marrow or the total body. Results: A red marrow absorbed dose-dependent effect on hematological parameters was observed, which could be evaluated by a decrease in blood cell counts. The absorbed dose to the bone marrow, corresponding to the maximal tolerable activity that could safely be administered, was determined to 8.3 Gy for (177)Lu and 12.5 Gy for (90)Y. Conclusions: There was a clear correlation between the hematological effects, quantified with some of the studied parameters, and the calculated red marrow absorbed doses. The decline in body weight was stronger correlated to the total body absorbed dose, rather than the red marrow absorbed dose. Finally, when considering a constant activity concentration, the phantom weight, ranging from 225 g to 300 g, appeared to have no substantial effect for the estimated absorbed dose.
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| 33. |
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| 34. |
- Lindh, Magnus, 1960, et al.
(författare)
-
Dynamic tailoring of treatment durations improves efficiency of hepatitis C treatment with pegylated interferon and ribavirin
- 2013
-
Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1352-0504 .- 1365-2893. ; 20:4
-
Tidskriftsartikel (refereegranskat)abstract
- The treatment durations for hepatitis C are guided by the analysis of hepatitis C virus (HCV) RNA in blood at certain time points. This multicentre, randomized open label trial evaluated the utility and performance of individualized treatment durations guided by viral decline rates in 103 patients with HCV genotype 1 infection. Pegylated interferon 2a and ribavirin were given as standard of care (SOC) for 24, 48 or 72 weeks or as dynamic treatment (DT) for 24–72 weeks. The DT duration was based on the time point when log HCV RNA would reach 0 log copies/mL, as estimated by the second-phase decline. The rate of sustained virologic response was 63% for SOC and 54% for DT, but this difference was not significant in multiple regression analysis taking predictive factors such as interleukin-28B genotypes, age and baseline viremia into account (P = 0.45). The mean required treatment time per cured patient was 51 weeks for DT as compared with 58 weeks for SOC (P = 0.22) when given per protocol (n = 95) and was significantly shorter (42 vs 51 weeks) among patients who achieved undetectable HCV RNA (P = 0.01). We conclude that DT was feasible and increased efficiency. The estimated time point for 0 log viral copies/mL is a new and quantitative response variable, which may be used as a complement to the qualitative variable rapid virologic response. The outcome parameter treatment weeks per cured patient could become a useful tool for comparing treatment efficiency also in the era of directly acting antivirals.
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| 35. |
- Lindh, Magnus, 1960, et al.
(författare)
-
Hepatitis C treatment response kinetics and impact of baseline predictors.
- 2011
-
Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1365-2893 .- 1352-0504. ; 18:6, s. 400-407
-
Tidskriftsartikel (refereegranskat)abstract
- Summary. The optimal duration of treatment for hepatitis C virus (HCV) infections is highly variable but critical for achieving cure (sustained virological response, SVR). We prospectively investigated the impact of age, fibrosis, baseline viraemia and genotype on the early viral kinetics and treatment outcome. Patients treated with peginterferon alfa-2a and ribavirin in standard dosing were included: 49 with genotype 1 treated for 48 weeks and 139 with genotype 2 or 3 treated for 24 weeks. The reduced SVR rates in patients older than 45 years, with severe liver fibrosis or pretreatment viraemia above 400 000 IU/mL were strongly associated with slower second phase declines of HCV RNA. Genotype 2/3 infections responded more rapidly than genotype 1, reaching week 4 negativity (RVR) in 59%vs 22%. We conclude that baseline response predictors such as age, fibrosis and viral load were well reflected by the early viral kinetics as assessed by repeated HCV RNA quantifications. The kinetic patterns and the high relapse rate in genotype 2/3 patients without RVR suggest that this group might benefit from treatment durations longer than 24 weeks.
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| 36. |
- Lindh, Magnus, 1960, et al.
(författare)
-
IL28B polymorphisms determine early viral kinetics and treatment outcome in patients receiving peginterferon/ribavirin for chronic hepatitis C genotype 1
- 2011
-
Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1352-0504 .- 1365-2893. ; 18:7
-
Tidskriftsartikel (refereegranskat)abstract
- Single nucleotide polymorphisms (SNPs) upstream of IL28B predict the outcome of treatment in chronic hepatitis C virus (HCV) infection, but their impact on viral kinetics and relation to other predictors are not well known. Here, two SNPs, rs12979860 and rs8099917, were analysed and related to early viral kinetics during treatment in 110 patients with HCV genotype 1 infection. The reduction of HCV RNA after 7days of therapy was more pronounced (P<0.0001) in patients with CC(rs12979860) or TT(rs8099917) than in patients carrying TT(rs12979860) or GG(rs8099917), respectively. The two SNPs were in linkage disequilibrium (d' =1, r2 = 0.44), but CC(rs12979860) was less common (43% vs. 71%) than TT(rs8099917). Patients carrying both CC(rs12979860) and TT(rs8099917) genotypes achieved lower levels of HCV RNA at week 4 than those with CT or TT at rs12979860 and TT(rs8099917) (P=0.0004). The viral elimination was significantly influenced by rs12979860 independently of baseline viral load, age or fibrosis. This translated into high rates of sustained viral response (SVR) among patients carrying CC(rs12979860) despite the presence of high viral load at baseline (SVR 74%), high age (SVR 79%) or severe liver fibrosis (SVR 83%). We conclude that the IL28B variability influences the antiviral efficiency of interferon/ribavirin therapy and has a strong impact on SVR, independently of traditional response predictors. A combined assessment of these SNPs in conjunction with other response predictors may better predict outcome in difficult-to-treat patients.
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| 37. |
- Lindhqvist, Violetta, et al.
(författare)
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Comparison of the mitogenic activities of streptococcal protein-G and staphylococcal protein-A on human mononuclear cells
- 1989
-
Ingår i: Immunological Investigations. - : Informa UK Limited. - 0882-0139 .- 1532-4311. ; 18:7, s. 919-930
-
Tidskriftsartikel (refereegranskat)abstract
- In the present work we report data from experiments comparing the proliferative stimuli demonstrated by Streptococcal Protein-G and Staphylococcal Protein A on human peripheral blood mononuclear cells. Protein-G and Protein-A are presented to the cells in solution as well as linked to plastic or Sepharose beads, or incorporated within the cell wall of whole bacteria. The cellular response is measured by incorporation of 3H-thymidine in 72 hr cultures. The soluble and the immobilized forms of Protein-A, but not those of Protein-G, displayed high mitogenicity. Possible explanations for the absence of Protein-G induced mitogenicity are discussed.
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| 38. |
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| 39. |
- Mårtensson, Linda, et al.
(författare)
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A nonsurgical technique for blood access in extracorporeal affinity adsorption of antibodies in rats.
- 2007
-
Ingår i: Artificial Organs. - : Wiley. - 0160-564X .- 1525-1594. ; 31:4, s. 312-316
-
Tidskriftsartikel (refereegranskat)abstract
- Monoclonal antibodies for targeting cytotoxic conjugates to tumor cells are currently being evaluated together with extracorporeal affinity adsorption. The aim of the adsorption was to reduce undesired side effects in normal organs and to increase the tumor-to-normal tissue ratios. This technique is also applicable to several other therapeutic areas such as immune-mediated disorders, that is, autoimmunity, allergy, and transplantation rejection. We describe an improved technique for extracorporeal affinity adsorption of radiolabeled biotinylated antibodies in rats. Blood access is established through the tail artery and tail vein, without surgical insertion of permanent catheters. This technique is simple, does not require surgery, and causes only minimal stress to the animals. In addition, experiments can be carried out on several animals simultaneously. This new technique is of considerable benefit for studying extracorporeal affinity adsorption in rats, as experiments can be carried out with negligible anatomical and physiological interventions, compared to previously used techniques.
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| 40. |
- Mårtensson, Linda, et al.
(författare)
-
Determining maximal tolerable dose of the monoclonal antibody BR96 labeled with 90Y or 177Lu in rats: establishment of a syngeneic tumor model to evaluate means to improve radioimmunotherapy.
- 2005
-
Ingår i: Clinical Cancer Research. - 1078-0432. ; 11:19 Pt 2, s. 7104-7108
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: To evaluate therapeutic strategies, it is essential to use biological models reflecting important aspects of the clinical situation. The aim of the present study was to compare the maximal tolerable dose of the monoclonal antibody BR96 labeled with Y-90 or Lu-177 in immunocompetent rats. Maximal tolerable dose was defined as the highest activity that allows 100% of the animals to survive without clinical signs, such as infections, bleeding, or diarrhea, and with < 20% loss in body weight. Experimental Design: Increasing activity levels of BR96 labeled with Y-90 or Lu-177 were administered to groups of rats. Blood parameters, body weight, and general performance were monitored for 8 weeks. Results: Two days postinjection, all groups had decreased leukocyte counts down to 5% to 15% of initial values. Initiation of recovery (at 14-21 days) showed a dose-response relationship. All groups, except the group given the highest activity of Y-90 had complete resolution in their leukopenia. The decrease in platelets was delayed to days 7 to 14 postinjection with a dose dependent response regarding both severity of the nadir (10-40% of initial value) and the start of recovery. Animals in the groups given the highest activities of both Y-90 and Lu-177 exhibited skin infections on day 21. Conclusions: The results showed good reproducibility and dose-dependent toxicity for both radionuclides, indicating that the maximal tolerable dose for Lu-177 - BR96 (1,000 MBq/kg) is 1.7 times that for Y-90 - BR96 (600 MBq/kg) in rats. This model makes it feasible to evaluate strategies to escalate therapeutic doses to tumors without increasing normal tissue toxicity.
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| 41. |
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| 42. |
- Mårtensson, Linda, et al.
(författare)
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High-Dose Radioimmunotherapy Combined With Extracorporeal Depletion in a Syngeneic Rat Tumor Model
- 2010
-
Ingår i: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 116:4, s. 1043-1052
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of the current study was to investigate the possibility of increasing the maximal tolerated dose (MTD) of a tumor-selective radiolabeled antibody when radioimmunotherapy (RIT) is combined with extracorporeal depletion of radioimmunoconjugates from the circulation. Furthermore, the authors evaluated whether this increase in dose improved the therapeutic effect on solid manifest tumors in an immunocompetent animal model. METHODS: Rats were injected with high activities/body weight of lutetium (Lu-177)- or yttrium (Y-90)-labeled antibody conjugates (monoclonal antibody tetraazacyclododecanetetraacetic acid-biotin) and subjected to removal of the conjugate from the circulation by extracorporeal affinity adsorption treatment 24 hours postinjection. Myelotoxicity was assessed by analysis of blood parameters for 12 weeks. The effect of increased doses in combination with extracorporeal affinity adsorption treatment was evaluated with respect to myelotoxicity and therapeutic effect in a syngeneic rat colon cancer model. RESULTS: The MTD of Lu-177- or Y-90-labeled immunoconjugates could be increased 2.0x or 1.5x, respectively, when RIT was combined with extracorporeal affinity adsorption treatment. All animals treated with Lu-177- or Y-90-labeled antibodies showed persistent complete response of manifest tumors (approximately 10 x 15 mm) within 16 days postinjection. However, several animals showed disseminated disease 1.5 to 3 months postinjection. CONCLUSIONS: Extracorporeal affinity adsorption treatment is a method that safely and efficiently reduces myelotoxicity associated with RIT. Extracorporeal affinity adsorption treatment allows increased administered activity without increased toxicity, with the aim of increasing the absorbed dose to the tumor. However, because tumor/normal tissue radiosensitivity ratios are more favorable in rodents, it is not possible to draw any conclusions concerning the therapeutic efficacy of increased administered activity in combination with extracorporeal affinity adsorption treatment in this study. Targeted RIT with beta-emitting radionuclides seems not to be effective in microscopic disease, because metastases developed at sites without previously known disease. (C) 2010 American Cancer Society.
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| 43. |
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| 44. |
- Mårtensson, Linda, et al.
(författare)
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Improved tumor targeting and decreased normal tissue accumulation through extracorporeal affinity adsorption in a two-step pretargeting strategy
- 2007
-
Ingår i: Clinical Cancer Research. - 1078-0432. ; 13:18, s. 5572-5576
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Evaluation of the possibilities of reducing the accumulation of radiolabeled streptavidin in radiosensitive organs by extracorporeal affinity adsorption (ECAT). Experimental Design: Rats were injected with biotinylated antibody and subjected to removal of the antibodies from the circulation by ECAT 24 h after injection (avidin column). Animals were then injected with In-111-1,4,7,10-tetra-azacylododecane N,N',N '',N'''-tetraacetic acid (DOTA) streptavidin. In a third step, animals were subjected to a second ECAT 8 h after injection to remove the DOTA-streptavidin from the circulation (biotin column). Biodistribution and tumor targeting of DOTA-streptavidin 24 h after injection was determined. Results: Elimination of biotinylated antibody by ECAT before injection of DOTA-streptavidin increased the tumor targeting by 50%. In addition, the levels of DOTA-streptavidin in liver and lymph nodes were reduced by 60%, which implied a 4.3- and 3.8-fold increase of tumor-to-liver and tumor-to-lymph node ratios, respectively. By doing a second ECAT to remove DOTA-streptavidin from the circulation, accumulation in normal tissues was reduced. However, this latter ECAT also reduced tumor accumulation by 25% (mostly corresponding to radioactivity in the circulation). Conclusions: ECAT was efficient as a means of removing biotinylated antibodies and would probably also be efficient for the clearance of streptavidin-conjugated antibodies. Conversely, the use of ECAT for removal of radiolabeled streptavidin seems not to offer any advantage.
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| 45. |
- Mårtensson, Linda, et al.
(författare)
-
Reduced myelotoxicity with sustained tumor concentration of radioimmunoconjugates in rats after extracorporeal depletion.
- 2007
-
Ingår i: Journal of Nuclear Medicine. - 0161-5505. ; 48:2, s. 269-276
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the possibility of decreasing the myelotoxicity associated with radioimmunotherapy (RIT) by extracorporeal depletion of radioimmunoconjugates (RIC) from the circulation. The optimal combination of radionuclide and the time interval between injection of the RIC and the subsequent extracorporeal depletion procedure was assessed in immunocompetent rats, with respect to both myelotoxicity and tumor concentration of RIC. Methods: Rats were injected with (177)tumor Y-90-labeled antibody conjugate (mAb-DOTA-biotin) (mAb is monoclonal antibody; DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N",N'''-tetraacetic acid) and subjected to removal of the conjugate from the circulation by extracorporeal affinity adsorption treatment (ECAT) 12, 24, or 48 h after injection. Myelotoxicity was assessed by analysis of blood parameters for 10 wk. The effect of ECAT on the tumor concentration of RIC was evaluated in parallel by scintillation camera imaging in rats injected with In-111-labeled RIC. Results: ECAT reduced the blood content of RIC by 95%. Thus, myelotoxicity was significantly milder in animals subjected to ECAT than that in controls. The timing of ECAT influenced the rate and level of bone marrow recovery, with an earlier recovery in animals subjected to ECAT early after injection. The toxicity-reducing effect of ECAT was more distinct in animals injected with Lu-177-labeled RIC than in animals injected with 90Y-labeled RIC. Scintillation camera imaging of tumors before and after ECAT revealed that subjecting animals to ECAT at 12 h after injection considerably reduced the total activity in tumors (34%), whereas the effect was lower at both 24 h (18%) and 48 h (18%) after injection. Conclusion: ECAT can efficiently reduce myelotoxicity associated with RIT, and the concentration of RIC in tumor can be sustained, provided ECAT is performed at an optimal time after antibody administration. The choice of radionuclide for RIT in combination with ECAT is important, as the physical half-life is crucial for the toxicity-reducing potential of ECAT at a specific time.
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| 46. |
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| 47. |
- Nilsson, Jan-Eric, 1952-, et al.
(författare)
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Tidtabelläggning : principer, tumregler och utfall
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Denna rapport består av tre delar som ur olika perspektiv handlar om kapacitetstilldelning på järnväg. I rapportens första del beskrivs de principer och tumregler som används i avsaknad av det ideala instrumentet för att ta fram en tidtabell för varje nytt år. Ett centralt tillvägagångssätt för att hantera denna komplexa uppgift är att så långt som möjligt utgå från existerande tidtabell eftersom denna visat sig fungera i praktiken. Intervjuer pekar på att förhandskunskapen om denna prioriteringsordning kan påverka de ansökningar som lämnas, det vill säga att den eller de operatörer som från början vet att man kommer att ha lägre prioritet anpassar sina önskemål efter detta faktum.Rapportens andra del behandlar den del av prioriteringarna som avser balansgången mellan önskemål om att få bedriva trafik i förhållande till behovet av att få tillgång till banan för underhåll. En aspekt på denna del av problematiken är att Trafikverket tar på sig en central roll för att definiera behovet av tillgång till banan.Den tredje delen av rapporten använder data från tågplaneringsprocessen. Den centrala analysen syftar till att undersöka i vilken utsträckning olika operatörer och olika tågslag (person- eller godståg) beviljas de tåglägen som söks. Analysen indikerar att en stor del av de tåglägen som sökts i tågplanearbetet de senaste två åren också har beviljats.En avslutande diskussion pekar på att det kan finnas skäl att under vissa förutsättningar skapa utrymme för att också operatörer och entreprenörer kommunicerar direkt med varandra.
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| 49. |
- Nilsson, Lena, et al.
(författare)
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Association between vaccination and preventive routines on COVID-19-related mortality in nursing home facilities : a population-based systematic retrospective chart review
- 2022
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Ingår i: Primary Health Care Research and Development. - : Cambridge University Press. - 1463-4236 .- 1477-1128. ; 23
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Forskningsöversikt (refereegranskat)abstract
- Background:Older and frail individuals are at high risk of dying from COVID-19, and residents in nursing homes (NHs) are overrepresented in death rates. We explored four different periods during the COVID-19 pandemic to analyze the effects of improved preventive routines and vaccinations, respectively, on mortality in NHs. Methods:We undertook a population-based systematic retrospective chart review comprising 136 NH facilities in southeast Sweden. All residents, among these facilities, who died within 30 days after a laboratory-verified COVID-19 diagnosis during four separate 92-day periods representing early pandemic (second quarter 2020), middle of the pandemic (fourth quarter 2020), early post-vaccination phase (first quarter 2021), and the following post-vaccination phase (second quarter 2021). Mortality together with electronic chart data on demographic variables, comorbidity, frailty, and cause of death was collected. Results:The number of deaths during the four periods was 104, 120, 34 and 4, respectively, with a significant reduction in the two post-vaccination periods (P < 0.001). COVID-19 was assessed as the dominant cause of death in 20 (19%), 19 (16%), 4 (12%) and 1 (3%) residents in each period (P < 0.01). The respective median age in the four studied periods varied between 87and 89 years, and three or more diagnoses besides COVID-19 were present in 70-90% of the respective periods study population. Considerable or severe frailty was found in all residents. Conclusions:Vaccination against COVID-19 seems associated with a reduced number of deaths in NHs. We could not demonstrate an effect on mortality merely from the protective routines that were undertaken.
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| 50. |
- Nilsson, Lena, et al.
(författare)
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COVID-19 as the sole cause of death is uncommon in frail home healthcare individuals : a population-based study
- 2021
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Ingår i: BMC Geriatrics. - : BMC. - 1471-2318. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDuring the first pandemic wave, Sweden experienced a high mortality rate. Home healthcare reflects a group of people especially vulnerable to coronavirus disease 2019 (COVID-19). We aimed to evaluate the pattern of comorbidity and frailty in a group of individuals having fatal outcomes in home healthcare during the COVID-19 pandemic March to September 2020, and to assess the contribution of COVID-19 in the fatal outcomes.MethodsA cohort of adults with confirmed COVID-19 diagnosis that deceased in home healthcare between March and September 2020 were analysed in a retrospective study comprising home healthcare in 136 facilities in one Swedish county. Main outcome measures were comorbidity and frailty.ResultsOne hundred fifty-five individuals (88 women, 67 men) aged 57-106 (median 88) years were included in the analysis. Nine had considerable frailty (ability to perform various activities of daily living but confined to bed or chair on occasion) and the remaining 146 had severe frailty (unable to perform activities of daily living and/or confined to bed or chair; dementia necessitating care). Three or more diagnoses besides COVID-19 were present in 142 individuals and another eight had two diagnoses in addition to COVID-19. In 20 (13%) individuals, COVID-19 was assessed as the principal cause of death, in 100 (64.5%) a contributing cause, and for the remaining 35 (22.5%) death was probably caused by another comorbidity. This seemed to change over the course of the COVID -19 pandemic, with its contributing role decreasing from the middle of the summer.ConclusionsDeath in home healthcare during the first wave of the pandemic mostly affected individuals with severe frailty and comorbidity at very advanced ages. One fifth of the individuals who died in home health care had another cause than Covid-19.Trial registrationClinical Trials.gov NCT04642196 date 24/11/2020.
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