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Sökning: WFRF:(Norrgren H)

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  • Waldenström, Jesper, 1985, et al. (författare)
  • Randomized Trial Evaluating the Impact of Ribavirin Mono-Therapy and Double Dosing on Viral Kinetics, Ribavirin Pharmacokinetics and Anemia in Hepatitis C Virus Genotype 1 Infection
  • 2016
  • Ingår i: PLoS ONE. - : Public Library of Science. - 1932-6203. ; 11:5
  • Tidskriftsartikel (refereegranskat)abstract
    • In this pilot study (RibaC), 58 hepatitis C virus (HCV) genotype 1 infected treatment-naive patients were randomized to (i) 2 weeks ribavirin double dosing concomitant with pegylated interferon-alpha (pegIFN-alpha), (ii) 4 weeks ribavirin mono-therapy prior to adding pegIFN-alpha, or (iii) standard-of-care (SOC) ribavirin dosing concurrent with pegIFN-alpha. Four weeks of ribavirin mono-therapy resulted in a mean 0.46 log(10) IU/mL HCV RNA reduction differentially regulated across IL28B genotypes (0.89 vs. 0.21 log(10) IU/mL for CC and CT/TT respectively; P = 0.006), increased likelihood of undetectable HCV RNA week 4 after initiating pegIFN-alpha and thus shortened treatment duration (P < 0.05), and decreased median IP-10 concentration from 550 to 345 pg/mL (P < 0.001). Both experimental strategies impacted on ribavirin concentrations, and high levels were achieved after one week of double dosing. However, by day 14, double dosing entailed a greater hemoglobin decline as compared to SOC (2.2 vs. 1.4 g/dL; P = 0.03). Conclusion: Ribavirin down-regulates IP-10, and may have an antiviral effect differently regulated across IL28B genotypes.
  • Andersson, E., et al. (författare)
  • Increase in transmitted drug resistance in migrants from sub-Saharan Africa diagnosed with HIV-1 in Sweden
  • 2018
  • Ingår i: AIDS. - : Lippincott Williams & Wilkins. - 0269-9370. ; 32:7, s. 877-884
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To study the trends of transmitted drug resistance (TDR) in HIV-1 patients newly diagnosed in Sweden, 2010-2016. Design: Register-based study including all antiretroviral therapy-naive patients ≥18 years diagnosed with HIV-1 in Sweden 2010-2016. Methods: Patient data and viral pol sequences were extracted from the national InfCareHIV database. TDR was defined as the presence of surveillance drug resistance mutations (SDRMs). A CD4+ T-cell decline trajectory model estimated time of infection. Phylogenetic inference was used for cluster analysis. Chi-square tests and logistic regressions were used to investigate relations between TDR, epidemiological and viral factors. Results: One thousand, seven hundred and thirteen pol sequences were analyzed, corresponding to 71% of patients with a new HIV-1 diagnosis (heterosexuals: 53%; MSM: 34%). The overall prevalence of TDR was 7.1% (95% CI 5.8-8.3%). Nonnucleoside reverse transcriptase inhibitor (NNRTI) TDR increased significantly from 1.5% in 2010 to 6.2% in 2016, and was associated to infection and/or origin in sub-Saharan Africa (SSA). An MSM transmission cluster dating back to the 1990s with the M41L SDRM was identified. Twenty-five (1.5%) patients exhibited TDR to tenofovir (TDF; n = 8), emtricitabine/lamivudine (n = 9) or both (n = 8). Conclusion: NNRTI TDR has increased from 2010 to 2016 in HIV-1-infected migrants from SSA diagnosed in Sweden, mirroring the situation in SSA. TDR to tenofovir/emtricitabine, used in preexposure prophylaxis, confirms the clinical and epidemiological need for resistance testing in newly diagnosed patients.
  • Ydreborg, Magdalena, 1974, et al. (författare)
  • Impact of IL28B-Related Single Nucleotide Polymorphisms on Liver Transient Elastography in Chronic Hepatitis C Infection
  • 2013
  • Ingår i: Plos One. - : Public Library of Science. - 1932-6203. ; 8:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Aims: Recently, several genome-wide association studies have revealed that single nucleotide polymorphisms (SNPs) in proximity to IL28B predict spontaneous clearance of hepatitis C virus (HCV) infection as well as outcome following pegylated interferon and ribavirin therapy among genotype 1 infected patients. Additionally the presence of the otherwise favorable IL28B genetic variants in the context of HCV genotype 3 infection reportedly entail more pronounced liver fibrosis and steatosis. The present study aimed to evaluate the impact of IL28B SNP variability on liver stiffness as accessed by transient elastography. Methods: Seven hundred and seventy-one Swedish HCV infected patients sequentially undergoing liver stiffness measurement by means of Fibroscan (R) in the context of a real-life trial had samples available for IL28B genotyping (rs12979860) and HCV genotyping. Results: CCrs12979860 was more common among HCV genotype 2 or 3 infected treatment-naive patients than among those infected with genotype 1 (P<0.0001). Additionally CCrs12979860 among HCV genotype 3 infected patients was associated with higher liver stiffness values (P = 0.004), and higher AST to platelet ratio index (APRI; p = 0.02) as compared to carriers of the T allele. Among HCV genotype 1 infected patients, CCrs12979860 was significantly associated with higher viral load (P = 0.001), with a similar non-significant trend noted among HCV genotype 3 infected patients. Conclusion: This study confirms previous reports that the CCrs12979860 SNP is associated with more pronounced liver pathology in patients chronically infected with HCV genotype 3 as compared to genotype 1, suggesting that IL28B genetic variants differently regulates the course of HCV infection across HCV genotypes.
  • Aleman, Soo, et al. (författare)
  • A Risk for Hepatocellular Carcinoma Persists Long-term After Sustained Virologic Response in Patients With Hepatitis C-Associated Liver Cirrhosis
  • 2013
  • Ingår i: Clinical Infectious Diseases. - : Oxford University Press. - 1537-6591. ; 57:2, s. 230-236
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. The long-term effect of sustained virologic response (SVR) to antiviral therapy on the risk of developing hepatocellular carcinoma (HCC), liver complications, liver-related death, and overall death in hepatitis C virus (HCV)-infected patients with liver cirrhosis is not fully known. Methods. These risks were evaluated during long-term follow-up in 351 patients with HCV-related cirrhosis. One hundred ten patients with SVR, 193 with non-SVR, and 48 who were untreated were included in a multicenter cohort that was initiated in 2001 and prospectively followed up for a mean of 5.3 (SD, 2.8) years. Complementary follow-up data from national registries were used to minimize the loss of patients during follow-up. Results. Six patients with SVR developed HCC at 0.04, 0.64, 2.4, 7.4, 7.4, and 7.6 years, respectively, after achieving SVR. The incidences of HCC, any liver complication, liver-related death, and overall death per 100 person-years were significantly lower in SVR time with 1.0, 0.9, 0.7, and 1.9, compared to 2.3, 3.2, 3.0, and 4.1 in non-SVR and 4.0, 4.9, 4.5, and 5.1 in untreated time. The long-term consequences did not decline significantly after >3 years versus during the first 3 years of follow-up. Conclusions. The risk for HCC, liver decompensation, and death in patients with liver cirrhosis related to HCV was markedly reduced after SVR, but a long-term risk of developing HCC remains for up to 8 years. Cirrhotic patients with HCV who achieve SVR should therefore maintain long-term surveillance for HCC. Future studies aimed to better identify those with remaining long-term risk for HCC are needed.
  • Andersson, S, et al. (författare)
  • Human immunodeficiency virus (HIV)-2-specific T lymphocyte proliferative responses in HIV-2-infected and in HIV-2-exposed but uninfected individuals in Guinea-Bissau
  • 2005
  • Ingår i: Clinical and Experimental Immunology. - : British Society for Immunology. - 0009-9104. ; 139:3, s. 483-489
  • Tidskriftsartikel (refereegranskat)abstract
    • Human immunodeficiency virus (HIV)-2-specific T lymphocyte proliferative responses were determined in cultures of peripheral blood mononuclear cells from HIV-2-exposed uninfected individuals, HIV-2-infected individuals and HIV-negative controls in Guinea-Bissau. Increased HIV-2-specific T lymphocyte proliferative responses were detected in both groups compared to HIV-negative controls (healthy HIV-uninfected individuals without known exposure to an HIV-infected person); five out of 29 of the HIV-2-exposed uninfected and half (16 of 32) of the HIV-2-infected individuals had stimulation indexes >2, compared to one out of 49 of the HIV-negative controls (P = 0.003 and P < 0.0001, respectively). The exposed uninfected individuals had reactivity to a HIV-2 V3-peptide corresponding to amino acids 311-326 of the envelope glycoprotein, while the HIV-2-infected people reacted mainly to HIV-2 whole viral lysate. Thus, this study demonstrates a high degree of HIV-2-specific T helper cell activity, as measured by lymphocyte proliferation, in HIV-2-exposed uninfected individuals as well as in HIV-2-infected subjects. These immune responses could be important for resistance to the infection and for the control of established infection and, thus, play a role in the lower transmission and progression of HIV-2 compared to HIV-1.
  • Gisslén, M., et al. (författare)
  • Sweden, the first country to achieve the Joint United Nations Programme on HIV/AIDS (UNAIDS)/World Health Organization (WHO) 90-90-90 continuum of HIV care targets
  • 2017
  • Ingår i: HIV Medicine. - : Wiley-Blackwell. - 1464-2662 .- 1468-1293. ; 18:4, s. 305-307
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The Joint United Nations Programme on HIV/AIDS (UNAIDS)/World Health Organization (WHO) 90-90-90 goals propose that 90% of all people living with HIV should know their HIV status, 90% of those diagnosed should receive antiretroviral therapy (ART), and 90% of those should have durable viral suppression. We have estimated the continuum of HIV care for the entire HIV-1-infected population in Sweden. Methods: The Swedish InfCare HIV Cohort Study collects viral loads, CD4 counts, and viral sequences, along with demographic and clinical data, through an electronic clinical decision support system. Almost 100% of those diagnosed with HIV infection are included in the database, corresponding to 6946 diagnosed subjects living with HIV-1 in Sweden by 31 December 2015. Results: Using HIV surveillance data reported to the Public Health Agency of Sweden, it was estimated that 10% of all HIV-infected subjects in Sweden remain undiagnosed. Among all diagnosed patients, 99.8% were linked to care and 97.1% of those remained in care. On 31 December 2015, 6605 of 6946 patients (95.1%) were on ART. A total of 6395 had been on treatment for at least 6 months and 6053 of those (94.7%) had a viral load < 50 HIV-1 RNA copies/mL. Conclusions: The 2014 UNAIDS/WHO 90-90-90 goals for HIV care means that > 73% of all patients living with HIV should be virologically suppressed by 2020. Sweden has already achieved this target, with 78% suppression, and is the first country reported to meet all the UNAIDS/WHO 90-90-90 goals.
  • Ahmed, R K S, et al. (författare)
  • Antigen-specific beta-chemokine production and CD8(+) T-cell noncytotoxic antiviral activity in HIV-2-infected individuals
  • 2005
  • Ingår i: Scandinavian Journal of Immunology. - : Wiley-Blackwell. - 1365-3083 .- 0300-9475. ; 61:1, s. 63-71
  • Tidskriftsartikel (refereegranskat)abstract
    • Human immunodeficiency virus-2 (HIV-2) is less pathogenic than HIV-1, and the disease progression in HIV-2-infected individuals seems to be similar to that seen in HIV-1-infected long-term nonprogressors. Cell-mediated immune responses and the production of noncytotoxic CD8(+) T-cell antiviral factors (CAF) and beta-chemokines have been correlated to protection against HIV-1 and associated with asymptomatic infection and slower disease progression. We investigated the antigen-induced beta-chemokine production in HIV-2-infected patients living in Sweden and in Guinea-Bissau. We also compared in vitro CD8(+) T-cell-mediated noncytotoxic antiviral activity against beta-chemokine-sensitive R5 virus (HIV-1(Bal)) and beta-chemokine-insensitive X4 virus (HIV-1(IIIB)) in HIV-2-infected patients with that in HIV-1-infected patients. HIV-2-specific beta-chemokine production was demonstrated in a majority of the HIV-2-infected subjects. CD8(+) T cells of both HIV-1 and HIV-2-infected individuals suppressed R5 virus replication in vitro in a similar manner, while the inhibition of X4 virus replication seemed to be more frequent and of a higher magnitude among HIV-2-infected patients compared to HIV-1-infected subjects. Taken together, our results indicate that the production of CD8(+) T-cell noncytotoxic antiviral factors may contribute to the low transmission of the virus and slower disease progression in HIV-2-infected patients.
  • Bergman, Ake, et al. (författare)
  • Science and policy on endocrine disrupters must not be mixed : a reply to a "common sense" intervention by toxicology journal editors
  • 2013
  • Ingår i: Environmental health. - : BioMed Central. - 1476-069X .- 1476-069X. ; 12, s. 69-
  • Tidskriftsartikel (övrigt vetenskapligt)abstract
    • The "common sense" intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU.
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