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Sökning: WFRF:(Thulin Lars)

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1.
  • Boerma, M, et al. (författare)
  • A genetic polymorphism in connexin 37 as a prognostic marker for atherosclerotic plaque development
  • 1999
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 246:2, s. 211-218
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND OBJECTIVES: Atherosclerosis is a multifactorial disease, in part characterized by chronic inflammatory changes in the vessel wall and loss of normal physical and biochemical interactions between endothelial cells and smooth muscle cells. Previous studies [Hu J., Cotgreave IA. J Clin Invest; 99: 1-5] have provided molecular links between inflammation and myoendothelial communication via gap junctions, suggesting that these structures may be important in the development of the atherosclerotic vessel phenotype. In order to strengthen this premise, the aim of the present work was to probe for structural polymorphisms in connexin 37, a gap junctional protein uniquely expressed in endothelial cells, and to assess for potential genotypic segregation in individuals displaying atherosclerotic plaque. METHODS AND RESULTS: Computer-based comparisons of Expressed Sequence Tags (ESTs) predicted a polymorphism in the human gap junctional protein connexin 37 (cx37). The C1019-T mutation results in a proline to serine shift at codon 319 (cx37*1-cx37*2). A Restriction Fragment Length Polymorphism (RFLP) assay, involving the insertion of a novel Drd I cleavage site in the proline variant revealed a statistically significant over-representation of the cx37*1 allele in association with atherosclerotic plaque-bearing individuals (Odds-ratio for the homozygote = 2.38, Chi2 = 7.693, P = 0.006), in comparison to individuals lacking plaque, irrespective of a history of hypertension. CONCLUSIONS: These data suggest that the C1019-T polymorphism in cx37 may provide 'single gene marker', which could be useful in assessing atherosclerotic plaque development, particularly in cardiovascular risk groups such as those with borderline hypertension.
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2.
  • Thulin, Åsa, et al. (författare)
  • Extracellular vesicles in atrial fibrillation and stroke
  • 2020
  • Ingår i: Thrombosis Research. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0049-3848 .- 1879-2472. ; 193, s. 180-189
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Atrial fibrillation (AF) is associated with a 5-fold increased risk of thromboembolic stroke. Extracellular vesicles (EVs) convey pathophysiological information and are possible biomarkers for risk of stroke. Methods: EVs were measured in 836 patients with AF (of which 280 were stroke cases) selected from the ARISTOTLE trial and in a cohort of unselected 70 year old individuals (n = 1007, reference material). EVs from platelets, leukocytes, erythrocytes and inflammatory endothelial cells were measured using flow cytometry and a solid-phase proximity ligation assay. Results: Concentrations of EVs were higher in the ARISTOTLE patients than in the PIVUS cohort for all the EV groups except EVs from endothelial cells (p < 0.0001). The distributions of the concentrations of the EVs were similar among the control group and the stroke cases for all of the sources of EVs in the ARISTOTLE study. EVs were modestly correlated with the levels of NT-ProBNP, Cystatin C, GDF-15 and D-dimer. Stronger correlations were found for platelet EVs as well as phosphatidyl serine positive EVs that were correlated with CD40 ligand in the ARISTOTLE study. Leukocyte EVs were correlated with IL-6 in both the ARISTOTLE and the PIVUS study, implicating them in different physiological processes. Conclusions: Higher levels of EVs were found in anticoagulated patients with AF and a higher risk of stroke than in a general population of similar age, possibly due to the high disease burden in AF patients. Our data with EVs representing a broad repertoire of activated blood cells in AF patients suggest that EVs are likely not a key mediator of occurrence of stroke in this population.
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3.
  • Bondeson, Lisa, et al. (författare)
  • Clinical outcomes in cancer patients with COVID-19 in Sweden.
  • 2021
  • Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 60:12, s. 1572-1579
  • Tidskriftsartikel (refereegranskat)abstract
    • The results of studies on the relationship between cancer and COVID-19 have been conflicting and therefore further studies are needed. We aimed to examine the incidence of COVID-19 among patients at one of the largest oncology departments in Sweden, and to evaluate and identify risk factors for poor outcomes, hospital care and death, associated with COVID-19 among cancer patients.This retrospective study included cancer patients at a single center who tested positive for SARS-CoV-2 by PCR either in hospital, primary health care center or commercial laboratory between 1 March and 14 August 2020. Clinical and demographic data were collected from the medical records. Logistic regression analysis was used to identify variables that associated the primary outcomes of need for hospital care and death within 30days of positive test.Of 10,774 patients from the Department of Oncology at Sahlgrenska University Hospital, 135 tested positive for SARS-CoV-2 (1.3%). Twenty-eight patients were excluded from further the data collection since they did not meet the inclusion criteria. Altogether, 107 cancer patients were included and the case fatality rate (CFR) was 12% (13) within 30days of confirmed SARS-CoV-2 infection by PCR. Increasing years of age (OR 1.10; CI 95% 1.03-1.18), palliative treatment intent (OR 15.7; CI 95% 1.8-135.8), and transition to end-of-life care (OR 52.0; CI 95% 3.7-735.6) were associated with increased odds of death within 30days. Male sex was associated with needing hospital care (OR 3.7; CI 95% 1.50-9.1).As in the general population, male sex was found to be at greater risk of needing hospital care for COVID-19, with terminal cancer disease, and older age increasing the odds of fatality. Compared to the general population, slightly more cancer patients had COVID-19. The CFR was within the lower range of others reported in cancer patients.
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4.
  • Boyce, SW, et al. (författare)
  • Impact of sodium-hydrogen exchange inhibition by cariporide on death or myocardial infarction in high-risk CABG surgery patients: Results of the CABG surgery cohort of the GUARDIAN study
  • 2003
  • Ingår i: Journal of Thoracic and Cardiovascular Surgery. - 1097-685X. ; 126:2, s. 420-427
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To evaluate the effects of cariporide on all-cause mortality or myocardial infarction at 36 days in patients at risk,of myocardial necrosis after coronary artery bypass graft surgery. Methods: In the coronary artery bypass graft cohort of the GUARD During Ischemia Against Necrosis trial, patients greater than or equal to 18 years who required urgent coronary artery bypass graft, repeat coronary artery bypass graft, or had a history of unstable angina and 2 :2 risk factors (age >65 years, female gender, diabetes mellitus, ejection fraction <35%, or left main or 3-vessel disease) were randomized to placebo (n = 743) or cariporide 20 mg (n = 736), 80 mg (n = 705), or 120 mg (n = 734). A 1-hour intravenous infusion was initiated shortly before surgery and administered every 8 hours for 2 to 7 days. Patients were followed up for 6 months. A nonparametric covariance analysis was used to calculate the primary efficacy endpoint. Results: Baseline characteristics were similar between treatment groups. The cariporide 20- and 80-mg groups had event rates similar to placebo. The endpoint of all-cause mortality or myocardial infarction at day 36 was significant with cariporide 120 mg versus placebo (event rate 12.2% vs 16.2%; P = .027). The risk reduction was evident on postoperative day 1 (3.3% vs 6.5%; P = .005) and was maintained at 6 months (event rate 15.0% vs 18.6%; P = .033). Cariporide was well tolerated, and most adverse events were mild and transient in this high-risk population. Conclusions: Clinical benefit with cariporide 120 mg was observed early after treatment initiation and continued for 6 months postsurgery, suggesting that sodium-hydrogen exchange inhibition with cariporide is cardioprotective in patients undergoing high-risk coronary artery bypass graft surgery.
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5.
  • Braunerhjelm, Pontus, et al. (författare)
  • The Relationship Between Domestic and Outward Foreign Direct Investment : The Role of Industry-Specific Effects
  • 2005
  • Ingår i: International Business Review. - Amsterdam : Elsevier. - 0969-5931 .- 1873-6149. ; 14:6, s. 677-694
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous research has been inconclusive as regards the effect of outward foreign direct investment (FDI) on domestic investments. In this article, we show that this inconclusiveness can be explained at a disaggregated level as a function of the way industries are organized. Based on a simple theoretical framework including monitoring and trade costs, we argue that a complementary relationship can be expected to prevail in vertically integrated industries, whereas a substitutionary relationship can be expected in horizontally organized production. The empirical analysis confirms a significant difference between the two categories of industry as regards the impact of outward FDI on domestic investment. The results may thus have profound policy implications.
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6.
  • Braunerhjelm, Pontus, et al. (författare)
  • The Relationship Between Domestic and Outward ForeignInvestment Revisited : The Impact of Industry-Specific Effects
  • 2005
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • The ambiguity reported in previous research as regards the effect of foreign direct investment(FDI) on domestic investments is shown to be related to how industries are organized. Basedon a simple model including monitoring and trade costs, we argue that a complementaryrelationship should prevail in vertically integrated industries, whereas a substitutionaryrelationship can be expected in horizontally organized production. Applying iterative SURtechnique,the empirical analysis confirms a significant difference between the two categoriesof industries. To our knowledge, this is the first attempt to reconcile the inconclusivenessreported in previous empirical analyses.
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7.
  • de Boer, Hugo J. (författare)
  • Snake Gourds, Parasites and Mother Roasting : Medicinal plants, plant repellents, and Trichosanthes (Cucurbitaceae) in Lao PDR
  • 2012
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background. Traditional plant use was studied in Lao PDR. Research focused on medicinal plant use by the Brou, Saek and Kry ethnic groups, traditional plant repellents against parasitic arthropods and leeches, and the phylogeny and biogeography of the medicinally-important snake gourd genus (Trichosanthes, Cucurbitaceae).  Methods. The ethnobiology research used a combination of structured interviews, village surveys, botanical collecting, hydro-distillation, GC-MS analysis, literature studies, and laboratory experiments. The plant systematics research used a combination of morphological studies, molecular biology laboratory work, and phylogenetic, dating and biogeographical analysis.  Results. Informants reported the use of close to 100 species to repel arthropods and leeches, many of which have constituents with documented efficacy.  Brou, Saek and Kry informants use over 75 plant species for women’s healthcare, mainly during the postpartum period for steam sauna, steam bath, hotbed, mother roasting, medicinal decoctions and infusions, and postpartum diet.  A molecular phylogeny of Trichosanthes and Gymnopetalum using a broad sampling of ~60% of their species and 4756 nucleotides of nuclear and plastid DNA shows that Gymnopetalum is nested within Trichosanthes. Fossil-calibrated Bayesian molecular dating of the Trichosanthes phylogeny reveals an early Oligocene origin of the genus, and many of the extant sections originating and diversifying during the Miocene. Biogeographical analysis shows a likely East or South Asian origin of Trichosanthes, with lineages diversifying and spreading throughout Australasia from the early Pliocene to the Pleistocene.  Discussion. Traditional plant use in Lao PDR is common and widespread. The presence among the repellent species of economical alternatives to costly synthetic repellents is tenable, and the subject of ongoing studies.  Postpartum traditions and medicinal plant use are essential parts of childbirth and postpartum recovery in these ethnic groups, and many other groups in Lao PDR. Efforts to improve maternal healthcare and reduce maternal and infant mortality need to integrate these traditions with modern notions of healthcare to achieve wider adoption. Documenting all possible uses of commonly used medicinal plant species shows that similarity in use between these ethnic groups is relatively low considering that they share, and have shared for many generations, the same environment and resources. A lack of effective cures leads to a process of continuous innovation, where effective cures are shared between cultures, but remedies of only cultural importance, or those under evaluation are culture-specific.  The Trichosanthes phylogeny implies the merging of Gymnopetalum into Trichosanthes, and this is done using available names or new combinations. A synopsis of Trichosanthes, the new combinations, and a revision of the species in Australia, are made and presented.  Conclusions. Traditional plant use is widespread in Lao PDR, and of significance to many people as a source of primary healthcare and inexpensive repellents. The important medicinal plant genus Trichosanthes includes Gymnopetalum, and has a complex biogeographic history with multiple colonization events of Australasia.
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8.
  • Dunberger, Gail, et al. (författare)
  • Cancer survivors' perception of participation in a long-term follow-up study.
  • 2013
  • Ingår i: Journal of medical ethics. - : BMJ. - 1473-4257 .- 0306-6800. ; 39:1, s. 41-5
  • Tidskriftsartikel (refereegranskat)abstract
    • Every year medical researchers make contact with a large number of cancer survivors with the aim of evaluating cancer treatment. For this reason we decided to investigate how Swedish cancer survivors perceived their participation in research studies focusing on the long-term consequences of being a survivor of gynaecological or urinary bladder cancer. Data were collected by means of two study-specific postal questionnaires, both consisting of questions covering physical symptoms, well-being and the experience of being a cancer survivor. Both questionnaires also included questions evaluating the participants' experience of being research subjects. The questionnaires were developed in close co-operation with cancer survivors. The study population consisted of 1068 cancer survivors. Of these, 95% (n=1003) reported that they thought the study was valuable and 54% (n=559) that they had been positively affected by participating. Four per cent (n=39) expressed that they had been negatively affected by their participation in the study. The vast majority of the cancer survivors thought that participating in their particular study was valuable.
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9.
  • Dyhrfort, Philip, et al. (författare)
  • Monitoring of Protein Biomarkers of Inflammation in Human Traumatic Brain Injury Using Microdialysis and Proximity Extension Assay Technology in Neurointensive Care
  • 2019
  • Ingår i: Journal of Neurotrauma. - : MARY ANN LIEBERT, INC. - 0897-7151 .- 1557-9042. ; 36:20, s. 2872-2885
  • Tidskriftsartikel (refereegranskat)abstract
    • Traumatic brain injury (TBI) is followed by secondary injury mechanisms strongly involving neuroinflammation. To monitor the complex inflammatory cascade in human TBI, we used cerebral microdialysis (MD) and multiplex proximity extension assay (PEA) technology and simultaneously measured levels of 92 protein biomarkers of inflammation in MD samples every three hours for five days in 10 patients with severe TBI under neurointensive care. One mu L MD samples were incubated with paired oligonucleotide-conjugated antibodies binding to each protein, allowing quantification by real-time quantitative polymerase chain reaction. Sixty-nine proteins were suitable for statistical analysis. We found five different patterns with either early (<48 h; e.g., CCL20, IL6, LIF, CCL3), mid (48-96 h; e.g., CCL19, CXCL5, CXCL10, MMP1), late (>96 h; e.g., CD40, MCP2, MCP3), biphasic peaks (e.g., CXCL1, CXCL5, IL8) or stable (e.g., CCL4, DNER, VEGFA)/low trends. High protein levels were observed for e.g., CXCL1, CXCL10, MCP1, MCP2, IL8, while e.g., CCL28 and MCP4 were detected at low levels. Several proteins (CCL8, -19, -20, -23, CXCL1, -5, -6, -9, -11, CST5, DNER, Flt3L, and SIRT2) have not been studied previously in human TBI. Cross-correlation analysis revealed that LIF and CXCL5 may play a central role in the inflammatory cascade. This study provides a unique data set with individual temporal trends for potential inflammatory biomarkers in patients with TBI. We conclude that the combination of MD and PEA is a powerful tool to map the complex inflammatory cascade in the injured human brain. The technique offers new possibilities of protein profiling of complex secondary injury pathways.
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10.
  • Edvinsson, Lars, et al. (författare)
  • Sensory nerve terminal activity in severe hypertension as reflected by circulating calcitonin gene-related peptide (CGRP) and substance P
  • 1992
  • Ingår i: Blood Pressure. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 1:4, s. 223-229
  • Tidskriftsartikel (refereegranskat)abstract
    • In patients with severe hypertension and in age and sex matched controls the circulating levels of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) and substance P-LI were measured. Samples were taken before medication, after 2-4 weeks and 2-12 months of pharmacological treatment to normotension. In the control group CGRP-LI levels were significantly higher for females than for males. No such relation was seen for substance P-LI. There were no correlations between CGRP-LI, substance P-LI or blood pressure. In the untreated acute hypertensive group there was a significant correlation between circulating levels of CGRP-LI and both diastolic and systolic blood pressure. No such relationship was seen for substance P-LI. The plasma levels of substance P-LI were significantly elevated (2.8 +/- 4.0) compared to controls (1.3 +/- 1.3, pmol/l, mean +/- S.D., p < 0.01). The levels of CGRP-LI did not differ from the control group. After 2-4 weeks of treatment the blood pressure decreased significantly and the plasma levels of substance P-LI were normalized while the CGRP-LI still did not differ from that of controls. After 2-12 months of treatment the blood pressure was still normalized, and the plasma levels of CGRP-LI and substance P-LI were not different from the control group. In the present study there was a positive correlation in hypertensives between the circulating CGRP-LI levels and diastolic and systolic blood pressure and elevated levels of substance P-LI. This would implicate the existence of a dynamic control through which the sensory system may register and damp the pressure response.
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11.
  • Enochsson, Lars, et al. (författare)
  • Kvalitetsregister för gallstenskirurgi har förbättrat vården
  • 2015
  • Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 112
  • Tidskriftsartikel (refereegranskat)abstract
    • The Swedish Registry for cholecystectomy and endoscopic retrograde cholangiopancreatography (ERCP) (GallRiks) is a validated register with high coverage. The registry started on May 1, 2005 and serves as a base for audit on gallstone disease treatment and also provides a database for clinical research. The aim of this study is to present an overview of the clinical consequences and implementations in patient care that GallRiks research may have contributed to during a 10-year period. Results from studies on GallRiks data have reduced the use of antibiotic and thromboembolic prophylaxis as well as showed the importance of intraoperative cholangiography. Furthermore, the studies on GallRiks data have most probably changed the treatment strategies in ERCP. Studies on GallRiks data have changed and improved the management of patients in Sweden who undergo gallstone surgery or ERCP.
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12.
  • Enochsson, Lars, et al. (författare)
  • The Swedish Registry of Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography (GallRiks) : A nationwide registry for quality assurance of gallstone surgery.
  • 2013
  • Ingår i: JAMA Surgery. - : American Medical Association (AMA). - 2168-6254 .- 2168-6262. ; 148:5, s. 471-8
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To describe the process of initiating and organizing a nationwide validated web-based quality registry of gallstone surgery and endoscopic retrograde cholangiopancreatography (ERCP) and to present some clinical data and the impact the registry has had on the clinical treatment of gallstones.DESIGN: Observational, population-based registry study.SETTING: Data from the nationwide Swedish Registry of Gallstone Surgery and ERCP (GallRiks).PATIENTS: From May 1, 2005, to December 31, 2011, 63 685 cholecystectomies (laparoscopic and open) and 37 860 ERCPs have been prospectively registered in GallRiks.INTERVENTIONS: Cholecystectomies, laparoscopic or conventional, as well as ERCP in a population-based setting.MAIN OUTCOME MEASURES: Registrations of all cholecystectomies and ERCPs are performed online by the surgeon or endoscopist. Thirty-day follow-up of both gallstone surgery and ERCP is mandatory, as is an additional 6-month follow-up of the cholecystectomies. Scores on the 36-Item Short Form Health Survey are registered preoperatively and 6 months postoperatively in elective cholecystectomies at selected units.RESULTS: The 30-day overall complication rate is 6.1% in elective cholecystectomy, 11.2% in urgent cholecystectomy, and 12.0% following ERCP. The use of antibiotic and thromboembolic prophylaxis in elective laparoscopic cholecystectomy in Sweden has decreased by 8.7% and 17.8% (2006-2011), respectively, mainly owing to presentation of GallRiks data both at meetings and published in peer-reviewed publications. The large database has also enabled several research projects, including one demonstrating that the intention to perform intraoperative cholangiography reduced the risk of death after cholecystectomy. The database has reached greater than 90% national coverage and is continuously validated.CONCLUSIONS: GallRiks is a validated national quality registry for gallstone surgery and ERCP, serving as a base for audit of gallstone disease treatment. It also provides a database for clinical research.
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13.
  • Erlinge, David, et al. (författare)
  • Neuropeptide Y-like immunoreactivity and hypertension
  • 1992
  • Ingår i: Journal of Hypertension. - 1473-5598. ; 10:10, s. 1221-1225
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Neuropeptide Y is a co-transmitter with noradrenaline in sympathetic neurons supplying arteries and veins with potent contractile effects. To investigate the role of neuropeptide Y in hypertension, we measured the circulating levels of neuropeptide Y and noradrenaline in patients with severe hypertension. DESIGN: Samples were collected from patients with untreated, severe hypertension (diastolic blood pressure > 120 mmHg) and in age- and sex-matched controls. After treatment with beta-adrenoceptor blockers, diuretics, angiotensin converting enzyme inhibitors of calcium antagonists, samples were taken from the patients during 12 months. METHODS: The circulating levels of neuropeptide Y-like immunoreactivity (NPY-LI) were measured with a radioimmunoassay using a rabbit antiserum. Catecholamines were measured using high-performance liquid chromatography and electrochemical detection. RESULTS: There was a significantly higher level of NPY-LI in the patients when they were compared with the controls. However, there was no correlation either in the controls or in the hypertensives between systolic blood pressure, diastolic blood pressure and NPY-LI or noradrenaline. The increased level of NPY-LI in plasma remained elevated for up to 12 months despite reduction in blood pressure to acceptable levels. The noradrenaline level was not increased before treatment, after 2-4 weeks or after 2-12 months treatment. CONCLUSION: The high level of NPY-LI may represent a marker for higher activity of the sympathetic nervous system which is not controlled by the treatment of blood pressure to normotension.
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14.
  • Fellström, Bengt, 1947-, et al. (författare)
  • Albumin Urinary Excretion Is Associated with Increased Levels of Urinary Chemokines, Cytokines, and Growth Factors Levels in Humans
  • 2021
  • Ingår i: Biomolecules. - : MDPI. - 2218-273X. ; 11:3
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the present study was to study the associations between urine albumin excretion, and a large number of urinary chemokines, cytokines, and growth factors in a normal population. We selected 90 urine samples from individuals without CVD, diabetes, stroke or kidney disease belonging to the Prospective Investigation of the Vasculature in Uppsala Seniors Study (41 males and 49 females, all aged 75 years). Urinary cytokine levels were analyzed with two multiplex assays (proximity extension assays) and the cytokine levels were correlated with urine albumin. After adjustment for sex, body mass index (BMI), estimated glomerular filtration rate (eGFR), smoking and multiplicity testing, 11 biomarkers remained significantly associated with urine albumin: thrombospondin 2, interleukin 6, interleukin 8, hepatocyte growth factor, matrix metalloproteinase-12 (MMP-12), C-X-C motif chemokine 9, tumor necrosis factor receptor superfamily member 11B, osteoprotegerin, growth-regulated alpha protein, C-X-C motif chemokine 6, oncostatin-M (OSM) and fatty acid-binding protein, intestinal, despite large differences in molecular weights. In this study, we found associations between urinary albumin and both small and large urine proteins. Additional studies are warranted to identify cytokine patterns and potential progression markers in various renal diseases.
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15.
  • Fellström, Bengt, 1947-, et al. (författare)
  • Associations Between Apolipoprotein A1, High-Density Lipoprotein Cholesterol, and Urinary Cytokine Levels in Elderly Males and Females
  • 2019
  • Ingår i: Journal of Interferon and Cytokine Research. - : Mary Ann Liebert Inc. - 1079-9907 .- 1557-7465. ; 40:2, s. 71-74
  • Tidskriftsartikel (refereegranskat)abstract
    • There exists a close relationship between cardiovascular diseases and chronic kidney disease. Apolipoprotein A1 and high-density lipoprotein (HDL) cholesterol are widely used as cardiovascular risk markers but they also have anti-inflammatory properties. The aim of this study was to investigate any associations between HDL levels and cytokine levels in urine. We randomly selected 90 urine samples from the Prospective Investigation of the Vasculature in Uppsala Seniors Study (41 males and 49 females). The samples were analyzed with 2 multiplex assays, Multiplex Inflammation I and Cardiovascular II kits (Olink Bioscience, Uppsala, Sweden). We analyzed the correlations between 158 cytokines in urine with apolipoprotein A1, HDL cholesterol, apolipoprotein B, and low-density lipoprotein cholesterol. There were strong correlations for apolipoprotein A1 and HDL cholesterol with individual cytokines. After adjustment for multiplicity testing, there were 33 significant correlations between apolipoprotein A1 and cytokine levels and 14 of these were also significantly correlated with HDL cholesterol. The strongest associations were observed for IL-1α, SPON2, RAGE, PAR-1, TRAIL-R2, IL-4RA, TNFRSF11A, and SCF. A total of 28 out of 33 correlations were negative, indicating a negative relationship between apolipoprotein A1 and urinary cytokines. The study shows a negative correlation between apolipoprotein A1 and HDL cholesterol and urinary cytokine levels. The finding is in agreement with the anti-inflammatory properties of HDL.
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16.
  • Fellström, Bengt, 1947-, et al. (författare)
  • Strong Associations Between Early Tubular Damage and Urinary Cytokine, Chemokine, and Growth Factor Levels in Elderly Males and Females
  • 2021
  • Ingår i: Journal of Interferon and Cytokine Research. - : Mary Ann Liebert Inc. - 1079-9907 .- 1557-7465. ; 41:8, s. 283-290
  • Tidskriftsartikel (refereegranskat)abstract
    • Acute tubular necrosis is associated with high mortality rates and it is important to develop new biomarkers for tubular damage. The aim of this study was to investigate the effect of early tubular damage on a large number of urinary cytokines, chemokines, and growth factors. We selected 90 urine samples from the Prospective Investigation of the Vasculature in Uppsala Seniors Study (41 males and 49 females). The tubular damage markers cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) were analyzed in the urine samples and urinary cytokine levels were analyzed with 2 multiplex assays (proximity extension assay). After adjustment for sex, body mass index, estimated glomerular filtration rate, smoking, and multiplicity testing using the false discovery rate approach, there remained 26 cytokines that correlated significantly with urine cystatin C, 27 cytokines that correlated with NGAL, and 66 cytokines that correlated with KIM-1. Tubular damage shows a strong association with urinary cytokines, chemokines, and growth factors. Our findings indicate that multiplex proteomics could be a promising new approach to explore the complex effects of tubular damage.
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17.
  • Garrido, Pablo, et al. (författare)
  • Experimental rewilding may restore abandoned wood-pastures if policy allows
  • 2021
  • Ingår i: AMBIO: A Journal of the Human Environment. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 20, s. 101-112
  • Tidskriftsartikel (refereegranskat)abstract
    • Large herbivores play key roles in terrestrial ecosystems. Continuous defaunation processes have produced cascade effects on plant community composition, vegetation structure, and even climate. Wood-pastures were created by traditional management practices that have maintained open structures and biodiversity for millennia. In Europe, despite the broad recognition of their biological importance, such landscapes are declining due to land-use changes. This calls for finding urgent solutions for wood-pasture conservation. To test whether introducing an ecological replacement of an extinct wild horse could have positive effects on wood-pasture restoration, we designed a 3-year rewilding experiment. Horses created a more open wood-pasture structure by browsing on seedlings and saplings, affected tree composition via selective browsing and controlled the colonization of woody vegetation in grassland-dominated areas. Thus, rewilding could be a potential avenue for wood-pasture restoration and biodiversity conservation. However, such benefits may not materialize without a necessary paradigm and political shift.
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18.
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19.
  • Grattan, MT, et al. (författare)
  • Leaflet arrest in St Jude Medical and CarboMedics valves: an experimental study
  • 2004
  • Ingår i: European Journal of Cardio-Thoracic Surgery. - : Oxford University Press (OUP). - 1010-7940. ; 25:6, s. 953-957
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Two patients who suffered acute failure of their St Jude Medical Masters aortic valve prostheses due to leaflet arrest that were unrelated to suture material are presented. It was hypothesized that the valves failed because force applied to bear upon the valve annulus caused the hinge mechanism to become restricted or to arrest. Methods: A study was designed to measure the force that would cause leaflet arrest in three sizes of St Jude Medical Masters valves and CarboMedics mechanical valves. A specially manufactured pushrod device was used to apply a variable force to the sewing cuff, low annulus level, or to the pivot guards of all the valves. Results: For every valve size tested, the St Jude Medical Masters valves required significantly less force applied than did the CarboMedics valves to cause one or both leaflets to arrest (P < 0.0004). Conclusions: A force applied on the valve ring of mechanical valves can cause leaflet arrest. The force required to arrest the leaflets is within an order of magnitude of that measured in other in vivo animal studies. We conclude that force on the valve rings in patients after aortic valve surgery could cause leaflet malfunction and even arrest in some patients. (C) 2004 Elsevier B.V. All rights reserved.
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20.
  • Hendriks, Kasper P., et al. (författare)
  • Global Brassicaceae phylogeny based on filtering of 1,000-gene dataset
  • 2023
  • Ingår i: Current Biology. - : Elsevier. - 0960-9822 .- 1879-0445. ; 33:19, s. 4052-4068
  • Tidskriftsartikel (refereegranskat)abstract
    • The mustard family (Brassicaceae) is a scientifically and economically important family, containing the model plant Arabidopsis thaliana and numerous crop species that feed billions worldwide. Despite its relevance, most phylogenetic trees of the family are incompletely sampled and often contain poorly supported branches. Here, we present the most complete Brassicaceae genus-level family phylogenies to date (Bras-sicaceae Tree of Life or BrassiToL) based on nuclear (1,081 genes, 319 of the 349 genera; 57 of the 58 tribes) and plastome (60 genes, 265 genera; all tribes) data. We found cytonuclear discordance between the two, which is likely a result of rampant hybridization among closely and more distantly related lineages. To eval-uate the impact of such hybridization on the nuclear phylogeny reconstruction, we performed five different gene sampling routines, which increasingly removed putatively paralog genes. Our cleaned subset of 297 genes revealed high support for the tribes, whereas support for the main lineages (supertribes) was moder-ate. Calibration based on the 20 most clock-like nuclear genes suggests a late Eocene to late Oligocene origin of the family. Finally, our results strongly support a recently published new family classification, dividing the family into two subfamilies (one with five supertribes), together representing 58 tribes. This includes five recently described or re-established tribes, including Arabidopsideae, a monogeneric tribe accommodating Arabidopsis without any close relatives. With a worldwide community of thousands of researchers working on Brassicaceae and its diverse members, our new genus-level family phylogeny will be an indispensable tool for studies on biodiversity and plant biology.
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21.
  • Jansson, Anna, et al. (författare)
  • Shaping the Swedish landscape: a future for the Gotland russ
  • 2016
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Tree encroachment and abandonment of pastures is an important cause of biodiversity loss in Sweden. In thisstudy, we evaluate the impact of all-year-around grazing by an ancient horse breed, the Gotland russ (GR),on tree encroachment. Twelve GR stallions were kept in 3 enclosures (lat: 59, long: 17, 4 GR/enclosure, 7ha forest and 3 ha open fields/enclosure) from May 2014 (age 1 yrs) until February 2016. Prior to the study,3 exclosures (EX, 5×42.5 m) where GR grazing was excluded were centered with the long side at the borderbetween forest and field. The field part of EX were further divided into four 5×5 m sections starting from theforest (1 to 4). Tree type (deciduous, spruce or pine), number and height were registered in the sections and theequivalent, grazed area adjacent to the EX on the 25th of February 2016. Body condition (BC) was assessedweekly using a 9 leveled scoring system. Individuals <4 were withdrawn, fed and reintroduced when BC was>4. Analysis of tree heights and numbers were made by procGLM in SAS. There was no difference in the totalnumber of deciduous trees (21±8 vs 25±8), spruces (2±1 vs 3±1) and pines (0.2±0.2 vs 0.8±0.2) between EXand grazed areas (P>0.05). In the grazed areas, the deciduous trees were shorter compared to the trees in EX(330±57 vs 780±70 mm, P<0.0001). There was no difference in spruce height (EX: 920±110 vs grazed areas:780±130 mm, P=0.31). In the grazed areas, tree height decreased from quarter 1 to 4 (1: 610±60, 2: 230±110, 3:140±90 and 4: 60±100 mm, P<0.0001) whereas in EX, the height increased (1: 740±60, 2: 570±150, 3: 810±90and 4: 960±100 mm, P<0.02). Four individuals (3 from the same enclosure) were withdrawn temporarily inFebruary 2015 due to BC <4. The study show that grazing by GR may inhibit encroachment by deciduoustrees and that BC was maintained in most individuals, despite the semi-feral conditions. The results providea new use for a threatened, ancient breed in landscape management.
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22.
  • Linder, Adam, et al. (författare)
  • Erysipelas Caused by Group A Streptococcus Activates the Contact System and Induces the Release of Heparin-Binding Protein.
  • 2010
  • Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 1523-1747 .- 0022-202X. ; 130, s. 1365-1372
  • Tidskriftsartikel (refereegranskat)abstract
    • Bacterial skin infections, such as erysipelas or cellulitis, are characterized by fever and a painful erythematous rash. Despite the high prevalence of these infections, little is known about the underlying pathogenic mechanisms. This is partly due to the fact that a bacterial diagnosis is often difficult to attain. To gain insight into the pathogenesis of erysipelas, we investigated the samples obtained from infected and noninfected areas of skin from 12 patients with erysipelas. Bacterial cultures, detection of specific streptococcal antibodies in convalescent sera, and immunohistochemical analyses of biopsies indicated group A streptococcal etiology in 11 of the 12 patients. Also, electron micrographs of erythematous skin confirmed the presence of group A streptococcal cells and showed a limited solubilization of the surface-attached M protein. Degradation of high-molecular-weight kininogen and upregulation of the bradykinin-1 receptor in inflamed tissues indicated activation of the contact system in 11 patients. Analyses of release of the vasoactive heparin-binding protein (HBP) showed increased levels in the infected as compared with the noninfected areas. The results suggest that group A streptococci induce contact activation and HBP release during skin infection, which likely contribute to the symptoms seen in erysipelas: fever, pain, erythema, and edema.Journal of Investigative Dermatology advance online publication, 28 January 2010; doi:10.1038/jid.2009.437.
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24.
  • Sjögren, Johan, et al. (författare)
  • Cause of late death after cardiac surgery in the very elderly: a single institution experience.
  • 2002
  • Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1651-2006 .- 1401-7431. ; 36:2, s. 123-128
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: The referrals of elderly for cardiac surgery are increasing. The aim of this retrospective study is to review the long-term survival and to identify causes of late death in elderly after cardiac surgery. DESIGN: Between 1990 and 1993, 130 octogenarians underwent cardiac surgery in our department. A majority (88%) had elective surgery. One hundred and nine patients (84%) were in New York Heart Association functional class III or IV, preoperatively. Mean follow-up time was 5.4 +/- 2.5 years (range 0-10 years). Follow-up was 100% complete. RESULTS: Hospital mortality was 3.8% (5/130). Actuarial survival at 1 and 5 years were 90.0 +/- 2.6% (n = 117) and 62.3 +/- 4.3% (n = 81), respectively. Forty-six operative survivors died from cardiac-related death during follow-up. Multivariate predictors of postoperative death were higher age, poor left ventricular ejection fraction, preoperative renal insufficiency and combined surgical procedures. CONCLUSION: Our results in this paper indicate that cardiac-related mortality represents the majority of late deaths after cardiac surgery in octogenarians.
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25.
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26.
  • Sjögren, Johan, et al. (författare)
  • Quality of life in the very elderly after cardiac surgery: a comparison of SF-36 between long-term survivors and an age-matched population.
  • 2004
  • Ingår i: Gerontology. - : S. Karger AG. - 1423-0003 .- 0304-324X. ; 50:6, s. 407-410
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Background:</i> Octogenarians are the fastest growing section of the population in Western countries. Since health care resources are limited, there is a need for critical evaluations of the long-term surgical outcome and quality of life in the elderly. <i>Objectives:</i> Our aim was to assess the quality of life and long-term survival after cardiac surgery in the very elderly. <i>Methods:</i> Between 1990 and 1993, 117 octogenarians underwent aortic valve replacement, coronary artery bypass grafting or combined surgery at our department. Forty-one patients were still alive at the time of follow-up (mean 8.3 ± 1.9 years). Thirty-nine of the 41 long-term survivors (95%) answered a quality of life questionnaire (SF-36). The scores were compared with an age-matched population. <i>Results:</i> The overall survival at 1, 5 and 9 years was 92.3 ± 2.5, 65.0 ± 4.4 and 37.9 ± 5.2%, respectively. A significant difference was identified between the scores of our patients and the general Swedish octogenarians in two SF-36 headings (Bodily Pain and Physical Functioning). Our patients indicated lower physical function, but less pain in comparison with the general aged population. There was no significant difference in six of the eight SF-36 headings. <i>Conclusions:</i> The overall long-term survival was similar to Swedish octogenarians. Late postoperative quality of life in our long-term survivors was comparable to an age-matched population. Our findings support the view that a selected population of elderly may undergo open heart surgery with good long-term quality of life.
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29.
  • Thulin, Helena, et al. (författare)
  • Defecation disturbances after cystectomy for urinary bladder cancer
  • 2011
  • Ingår i: BJU International. - : Blackwell Publishing Ltd. - 1464-4096 .- 1464-410X. ; 108:2, s. 196-203
  • Tidskriftsartikel (refereegranskat)abstract
    • What’s known on the subject? and What does the study add?Functional gastrointestinal symptoms and problems are common after radical cystectomy with urinary diversion. This study adds new important epidemiological data on this group of symptoms. OBJECTIVE: To describe and compare long-term defecation disturbances in patients who had undergone a cystectomy due to urinary bladder cancer with non-continent urostomies, continent reservoirs and orthotopic neobladder urinary diversions. PATIENTS AND METHODS: During their follow-up we attempted to contact all men and women aged 30–80 years who had undergone cystectomy and urinary diversion at seven Swedish hospitals. During a qualitative phase we identified defecation disturbances as a distressful symptom and included this item in a study-specific questionnaire together with free-hand comments. The patients completed the questionnaire at home. Outcome variables were dichotomized and the results are presented as relative risks with 95% confidence interval. RESULTS: The questionnaire was returned from 452 (92%) of 491 identified patients. Up to 30% reported problems with the physiological emptying process of stool (bowel movement, sensory rectal function, awareness of need for defecation, motoric rectal and anal function, straining ability). A sense of decreased straining capacity was reported by 20% of the men and women with non-continent urostomy and 14% and 8% of those with continent reservoirs and orthotopic neobladders, respectively. CONCLUSIONS: Of the cystectomized individuals 30% reported problems with the physiological emptying process of stool (bowel movement, sensory rectal function, awareness of need for defecation, motoric rectal and anal function, straining ability). Those wanting to improve the situation for bladder cancer survivors may consider communicating before surgery the possibility of stool-emptying problems, and asking about them after surgery.
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30.
  • Thulin, Helena, et al. (författare)
  • Hygiene and urinary tract infections after cystectomy in 452 Swedish survivors of bladder cancer.
  • 2009
  • Ingår i: BJU International. - 1464-4096 .- 1464-410X.
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES To determine whether or not an improved hygiene can lessen the incidence of symptomatic urinary tract infections (UTIs) in patients treated by cystectomy for urinary bladder cancer. PATIENTS AND METHODS We attempted to contact during their follow-up all men and women aged 30-80 years who had undergone cystectomy and urinary diversion at seven Swedish hospitals. During a qualitative phase we identified hygienic measures and included them in a study-specific questionnaire. The patients completed the questionnaire at home. Outcome variables were dichotomized and the results presented as relative risks (RR) with 95% confidence interval. RESULTS We received the questionnaire from 452 (92%) of 491 identified patients. The proportion of patients who had a symptomatic UTI in the previous year was 22% for orthotopic neobladder and cutaneous continent reservoir, and 23% for non-continent urostomy diversion. The RR for a UTI was 1.1 (0.5-2.5) for 'never washing hands' before handling with catheters or ostomy material. Patients with diabetes mellitus had a RR of 2.1 (1.4-3.2) for having a symptomatic UTI. CONCLUSIONS We could not confirm lack of hygiene measures as a cause of UTI for men and women who had a cystectomy with urinary diversion. Patients with diabetes mellitus have a greater risk of contracting a UTI.
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31.
  • Thulin, Helena, et al. (författare)
  • Sleep disturbances decrease self-assessed quality of life in individuals who have undergone cystectomy.
  • 2010
  • Ingår i: The Journal of urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 184:1, s. 198-202
  • Tidskriftsartikel (refereegranskat)abstract
    • The best possible urinary diversion after cystectomy, if any, is yet to be defined to our knowledge. Therefore, we investigated nocturnal urinary disturbances and quality of life in individuals who have undergone cystectomy with urinary diversion for bladder cancer.
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32.
  • Thulin, Petra, et al. (författare)
  • Keratin-18 and microRNA-122 complement alanine aminotransferase as novel safety biomarkers for drug-induced liver injury in two human cohorts
  • 2014
  • Ingår i: Liver international (Print). - : Wiley. - 1478-3223 .- 1478-3231. ; 34:3, s. 367-378
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS:There is a demand for more sensitive, specific and predictive biomarkers for drug-induced liver injury (DILI) than the gold standard used today, alanine aminotransferase (ALT). The aim of this study was to qualify novel DILI biomarkers (keratin-18 markers M65/M30, microRNA-122, glutamate dehydrogenase and alpha-foetoprotein) in human DILI.METHODS:Levels of the novel biomarkers were measured by enzyme-linked immunosorbent assay or real-time quantitative reverse-transcription PCR (qRT-PCR) in two human DILI cohorts: a human volunteer study with acetaminophen and a human immunodeficiency virus (HIV)/tuberculosis (TB) study.RESULTS:In the acetaminophen study, serum M65 and microRNA-122 levels were significantly increased at an earlier time point than ALT. Furthermore, the maximal elevation of M65 and microRNA-122 exceeded the increase in ALT. In the HIV/TB study, all the analysed novel biomarkers increased after 1 week of treatment. In contrast to ALT, the novel biomarkers remained stable in a human cohort with exercise-induced muscular injury.CONCLUSIONS:M65 and microRNA-122 are potential biomarkers of DILI superior to ALT with respect to sensitivity and specificity.
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33.
  • Thulin, Ulrika, et al. (författare)
  • The Effect of Parent Involvement in the Treatment of Anxiety Disorders in Children : A Meta-Analysis
  • 2014
  • Ingår i: Cognitive Behaviour Therapy. - : Informa UK Limited. - 1650-6073 .- 1651-2316. ; 43:3, s. 185-200
  • Tidskriftsartikel (refereegranskat)abstract
    • Among clinicians, it is common practice to include parents in treatment, and it has been taken for granted that parents' involvement in their children's treatment is beneficial for therapy outcome, although research on this issue is far from clear. A meta-analysis was carried out in order to investigate whether parent involvement potentiates the outcome for children with anxiety disorders when treated with cognitive-behavior therapy. Sixteen studies, which directly compared parent-involved treatments with child-only treatments, were included in the meta-analysis. The results showed a small, nonsignificant effect size of -0.10 in favor of the child-only treatments. There was no indication of publication bias in the analysis. Implications of the results are discussed.
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34.
  • Vigerland, Sarah, et al. (författare)
  • Internet-Delivered CBT for Children with Specific Phobia : A Pilot Study
  • 2013
  • Ingår i: Cognitive Behaviour Therapy. - : Informa UK Limited. - 1650-6073 .- 1651-2316. ; 42:4, s. 303-314
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cognitive behavior therapy (CBT) has been shown to be an effective treatment for specific phobia in youth, but not all affected seek or receive treatment. Internet-delivered CBT could be a way to increase the availability of empirically supported treatments. Aims: An open trial was conducted to evaluate Internet-delivered CBT for children with specific phobia. Method: Children (N=30) aged 8-12, and their parents, with a principal diagnosis of specific phobia were recruited through media advertisement. Participants received six weeks of Internet-delivered CBT with therapist support. The treatment was aimed for the parents and the children, with the first part being only for the parents. The primary outcome measure was the Clinician Severity Rating (CSR), and secondary measures included clinician-rated global functioning and child- and parent-reported anxiety and quality of life. All assessments were made at pretreatment, posttreatment, and three-month follow-up. Results: At posttreatment, there were significant reductions on the CSR, with a large within-group effect size (Cohen's d=1.0) and 35% of children no longer meeting criteria for specific phobia. Self-report measures from parents and children showed significant effects on anxiety, with small to moderate effect sizes. Effects were maintained at three-month follow-up. Conclusions: Results show that Internet-delivered CBT with therapist support for children with specific phobia has the potential to reduce symptom severity. Randomized controlled trials are needed to further evaluate this treatment format.
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35.
  • Vigerland, Sarah, et al. (författare)
  • Internet-delivered cognitive behavioural therapy for children with anxiety disorders : A randomised controlled trial
  • 2016
  • Ingår i: Behaviour Research and Therapy. - : Elsevier BV. - 0005-7967 .- 1873-622X. ; 76, s. 47-56
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cognitive behaviour therapy (CBT) has been shown to be an effective treatment for anxiety disorders in children, but few affected seek or receive treatment. Internet-delivered CBT (ICBT) could be a way to increase the availability of empirically supported treatments.Aims: A randomised controlled trial was conducted to evaluate ICBT for children with anxiety disorders.Method: Families (N = 93) with a child aged 8–12 years with a principal diagnosis of generalised anxiety disorder, panic disorder, separation anxiety, social phobia or specific phobiawere recruited through media advertisement. Participants were randomised to 10 weeks of ICBT with therapist support, or to a waitlist control condition. The primary outcome measure was the Clinician Severity Rating (CSR) and secondary measures included child- and parent-reported anxiety. Assessments were made at pre-treatment, post-treatment and at three-month follow-up.Results: At post-treatment, there were significant reductions on CSR in the treatment group, with a large between-group effect size (Cohen's d = 1.66). Twenty per cent of children in the treatment group no longer met criteria for their principal diagnosis at post-treatment and at follow-up this number had increased to 50%. Parent-reported child anxiety was significantly lower in the treatment group than in the waitlist group at post-treatment, with a small between-group effect size (Cohen's d = 0.45). There were no significant differences between the groups regarding child-ratings of anxiety at post-treatment. Improvements were maintained at three-month follow-up, although this should be interpreted cautiously due to missing data.Conclusions: Within the limitations of this study, results suggest that ICBT with therapist support for children with anxiety disorders can reduce clinician- and parent-rated anxiety symptoms.Trial registration: Clinicaltrials.gov: NCT01533402.
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