| 1. |
- Bartosik, I, et al.
(författare)
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Correlation between plasma concentrations of calcitonin gene related peptide and pulmonary pressure in patients with systemic sclerosis.
- 2002
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 61:3, s. 261-263
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine plasma levels of calcitonin gene related peptide (p-CGRP) in patients with systemic sclerosis (SSc) and pulmonary hypertension (PH). MATERIAL AND METHODS: Twenty nine patients with SSc, 10 with diffuse form, 18 with limited form and one with overlapping systemic lupus erythematosus were examined. Twelve patients displayed normal systolic pulmonary artery pressure (PAPsyst) < or =30 mm Hg and 17 increased PAPsyst
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| 2. |
- Chizzolini, C, et al.
(författare)
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Systemic sclerosis Th2 cells inhibit collagen production by dermal fibroblasts via membrane-associated tumor necrosis factor alpha
- 2003
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 48:9, s. 2593-2604
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Tidskriftsartikel (refereegranskat)abstract
- Objective. In systemic sclerosis (SSc; scleroderma), T cells infiltrate organs undergoing fibrotic changes and may participate in dysregulated production of collagen by fibroblasts. The objective of this study was to functionally characterize T cells infiltrating skin lesions in early SSc and investigate their capacity to affect production of type I collagen and interstitial collagenase (matrix metalloproteinase 1 [MMP-1]) by dermal fibroblasts. Methods. Four-color cytometric analysis was used to characterize subset distribution and production of interferon-gamma (IFNgamma) and interleukin-4 (IL-4) in T cell lines generated from the skin of patients with SSc. T cell clones were generated, and their capacity to modulate collagen and MMP-1 production by fibroblasts derived from patients with SSc and from normal individuals was assessed. Neutralizing reagents were used to identify T cell mediators involved in fibroblast modulation. Results. The skin of individuals with early-stage SSc contained T cells preferentially producing high levels of IL-4. Cloned CD4+ Th2-like cells inhibited collagen production by normal fibroblasts. Th2 cell-dependent inhibition was, at least in part, contact-dependent, was essentially mediated by tumor necrosis factor alpha (TNFalpha), and was dominant over the enhancement induced by profibrotic IL-4 and transforming growth factor beta cytokines. The simultaneous induction of MMP-1 production confirmed the specificity of these observations. To be inhibitory, Th2 cells required activation by CD3 ligation. Th2 cells were less potent than were Th1 cells in inhibiting collagen production by normal fibroblasts via cell-to-cell interaction, and SSc fibroblasts were resistant to inhibition. Conclusion. These findings indicate that, despite their production of IL-4, Th2 cells reduce type I collagen synthesis by dermal fibroblasts because of the dominant effect of TNFalpha, and suggest that strategies based on TNFalpha blockade aimed at controlling fibrosis in SSc may be unwise.
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| 3. |
- Denton, Christopher P., et al.
(författare)
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Recombinant human anti-transforming growth factor beta 1 antibody therapy in systemic sclerosis - A multicenter, randomized, placebo-controlled phase I/II trial of CAT-192
- 2007
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 56:1, s. 323-333
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To evaluate CAT-192, a recombinant human antibody that neutralizes transforming growth factor beta 1 (TGF beta 1), in the treatment of early-stage diffuse cutaneous systemic sclerosis (dcSSc). Methods. Patients with SSc duration of < 18 months were randomly assigned to the placebo group or to 1 of 3 CAT-192 treatment groups: 10 mg/kg, 5 mglkg, 0.5 mg/kg. Infusions were given on day 0 and weeks 6, 12, and 18. The primary objective of this study was to evaluate the safety, tolerability, and pharmacokinetics of CAT-192. Secondary outcomes included the modified Rodnan skin thickness score (MRSS), the Scleroderma Health Assessment Questionnaire, assessment of organ-based disease, serum levels of soluble interleukin-2 receptor, collagen propeptides (N propeptide of type I [PINP] and type III collagen), and tissue levels of messenger RNA for procollagens I and III and for TGF beta 1 and TGF beta 2. Results. Forty-five patients were enrolled. There was significant morbidity and mortality, including I death in the group receiving 0.5 mg/kg of CAT-192 and 3 deaths in the group receiving 5 mg/kg of CAT-192. There were more adverse events and more serious adverse events in patients receiving CAT-192 than in those receiving placebo, although these events were not more frequent in the high-dose treatment group. The MRSS improved in all groups during the study, but there was no evidence of a treatment effect for CAT-192. Improvement in the MRSS correlated with the disease duration (r = -0.54, P = 0.0008). Changes in the PINP level from baseline correlated with changes in the MRSS (r = 0.37, P = 0.027). Conclusion. We report the first evaluation of a systemically administered and repeatedly dosed anti-TGF beta 1 drug. In this pilot study, CAT-192, in doses up to 10 mg/kg, showed no evidence of efficacy. The utility of clinical and biochemical outcome measures and the feasibility of multicenter trials of early dcSSc were confirmed.
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| 4. |
- Hesselstrand, Roger, et al.
(författare)
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High-frequency ultrasound of skin involvement in systemic sclerosis reflects oedema, extension and severity in early disease.
- 2008
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 47:1, s. 84-87
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim was to compare skin assessment by palpation and by high-frequency ultrasound in patients with SSc with disease duration <2 yrs. METHODS: Skin thickness and skin echogenicity were measured by 20 MHz ultrasound at five different anatomical sites in 106 individuals within 2 yrs from the first non-Raynaud's symptom and compared with the modified Rodnan skin score (mRss). RESULTS: The patients with short disease duration were characterized by high skin thickness and low skin echogenicity, which correlated inversely, reflecting oedema. Patients with diffuse skin involvement displayed higher skin thickness and lower skin echogenicity than did patients with limited skin involvement. The ultrasound measurements correlated to the local mRss from the corresponding anatomical region and also to the total mRss. However, there was a considerable overlap in both skin thickness and skin echogenicity between different local mRss at all five anatomical sites. Skin involvement of the chest could be detected earlier by ultrasound than by palpation. CONCLUSION: In SSc patients with short disease duration, high-frequency ultrasound can identify the oedematous phase that may precede palpable skin involvement and may thus be useful to identify patients with diffuse skin involvement very early in the disease process. Ultrasound measurements also reflect the severity of the overall skin involvement.
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| 5. |
- Hesselstrand, Roger, et al.
(författare)
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Mortality and causes of death in a Swedish series of systemic sclerosis patients
- 1998
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Ingår i: Annals of the Rheumatic Diseases. - 1468-2060. ; 57:11, s. 682-686
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To analyse survival rates and the causes of death in a systemic sclerosis (SSc) population, and to evaluate the occurrence of fatal malignant neoplasms and their possible association with oral cyclophosphamide (CYC) treatment. METHODS: Survival was calculated for 249 SSc patients followed up for up to 13 years. Mean (SD) follow up was 5.8 (4.2) years. The 49 decreased patients were subdivided according to causes of death and its relation to SSc. Fatal malignancies in CYC treated patients were compared with those occurring in non-CYC treated patients. RESULTS: The overall 5 and 10 year survival rates were 86% and 69% respectively. There was a 4.6-fold increased risk of death, as compared with the general population. Prognosis was worse in the diffuse cutaneous involvement (dSSc) and male subgroups than in the limited cutaneous involvement (1SSc) and female subgroups. Of the 49 deaths, 24 were attributable to pulmonary complications such as pulmonary fibrosis, pulmonary hypertension, pneumonia or pulmonary malignancy. Treatment with oral CYC did not increase the risk of dying of cancer. CONCLUSIONS: Mortality is increased both in the SSc population as a whole and in its different subsets (dSSc and 1SSc). Prognosis is worst among male patients with dSSc. However, the 5 year survival rate was better than those reported from earlier studies. Most patients die of cardiopulmonary disease. Five of seven fatal lung cancers were adenocarcinomas, possibly caused by chronic inflammatory disease of the lung. In this study, CYC treatment was not associated with an increased incidence of fatal malignant neoplasms.
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| 6. |
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| 7. |
- Hesselstrand, Roger, et al.
(författare)
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The association between changes in skin echogenicity and the fibroblast production of biglycan and versican in systemic sclerosis
- 2002
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Ingår i: Clinical and Experimental Rheumatology. - 1593-098X. ; 20:3, s. 301-308
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate a possible association between the longitudinal changes in skin involvement and the fibroblast production of proteoglycans in vitro, among patients with early and untreated systemic sclerosis (SSc). Methods In 11 patients, 6 with diffuse cutaneous systemic sclerosis (dSSc) and 5 with limited cutaneous systemic sclerosis (lSSc), and in 6 controls skin thickness and skin echogenicity, of the forearm was measured by high frequency (20 MHz) ultrasound, A skin biopsy was taken from the area of the ultrasound measurements, and from cultivated fibroblasts the production of the proteoglycans versican, perlecan, biglycan and decorin were measured. To investigate longitudinal changes in skin involvement, the ultrasound examination was repeated after 1-3 years. Results Compared to controls, SSc Patients had increased skin thickness at the first evaluation. Patients with dSSc had lower skin echogenicity than both patients with ISSc and the controls. Patients with greater changes in skin thickness and skin echogenicity produced more versican, whereas the production of biglycan and decorin was higher only, in patients with greater changes in skin echogenicity. There was a negative correlation between fibroblast production of biglycan and disease duration. Conclusion High fibroblast synthesis of the proteoglycans versican and biglycan is associated with changes in skin echogenicity and may predict more progressive skin sclerosis in SSc.
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| 8. |
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| 9. |
- Kurti, Erdelina
(författare)
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Institutional Tensions and Complexity in the Digital Innovation of Incumbent Business Models
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Digitalization has influenced all areas of our lives, including businesses. It has provided numerous opportunities to organisations; at the same time, it has significantly challenged established business models in many sectors that were traditionally proven to be stable and successful, thus a need to innovate was called for. In this research the focus is on the newspaper industry, representing one of the contexts which has been highly affected by digitalization. Digital technologies enable new ways of operating which in turn challenge prevailing business assumptions and cause complexities. This leads to the aim of this research which is to explore institutional complexity in digital business model innovation in a newspaper organization.This research builds on business model theory, conceptualized as an activity system. It adds literature from digital innovation and finally utilizes institutional logics to explore the complexity emerging in the avenue of digital business model innovation. A case study design has been undertaken drawing on several data sources such as: interviews, observations and the study of documents.The outcome of this research illustrates that digitalization has a profound impact on business models of newspaper organizations. Innovation brought by digitalization entailed challenges but also enabled complementarities in value offering, activities, and competences, including new actors entering the market. The complementarities caused complexity based on different institutional logics, each with its own rationality, which needed to be governed. Research outcomes also include institutional mechanisms that were applied to govern the digital business model innovation, such as strategies leading to a hybrid of print and digital mode of operation; and also more concrete purposive actions and activities in the form of e.g. education and learning, theorization and top management commitment.This research contributes to the theoretical frameworks of business model innovation, digital business model innovation and institutional logics, both separately and in combination. Further, the research provides some recommendations to practice for managing the complexity that digitalization of incumbents entails.
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| 10. |
- Lagerlöf, Ingemar, et al.
(författare)
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No excess long-term mortality in stage I-IIA Hodgkin lymphoma patients treated with ABVD and limited field radiotherapy
- 2020
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Ingår i: British Journal of Haematology. - : John Wiley & Sons. - 0007-1048 .- 1365-2141. ; 188:5, s. 685-691
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Tidskriftsartikel (refereegranskat)abstract
- When treating limited stage classical Hodgkin lymphoma (cHL), balancing treatment efficacy and toxicity is important. Toxicities after extended-field radiotherapy are well documented. Investigators have aimed at reducing toxicity without compromising efficacy, mainly by using combined modality treatment (CMT), i.e. chemotherapy and limited-field radiotherapy. In some clinical trials, radiotherapy has been omitted. We evaluated 364 patients with stage I-IIA cHL treated between 1999 and 2005. Patients were treated with two or four cycles of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) according to presence of risk factors, followed by 30 Gy limited-field (reduced compared to involved-field) radiotherapy. After a median follow-up of 16 years for survival, freedom from progression at five and ten years was 93% and overall survival at 5 and 10 years was 98% and 96%, respectively. Only two relapses, out of 27, occurred after more than 5 years. There was no excess mortality compared to the general population. Of the analysed subgroups, only patients with progression within five years showed significant excess mortality. The absence of excess mortality questions the concept of omitting radiotherapy after short-term chemotherapy, a strategy that has been associated with an elevated risk of relapse but not yet with a proven reduced long-term excess mortality.
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