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- Bućin, Dragan, et al.
(author)
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Desensitization and Heart Transplantation of a Patient With High Levels of Donor-Reactive Anti-Human Leukocyte Antigen Antibodies.
- 2010
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In: Transplantation. - 1534-6080. ; 90, s. 1220-1225
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Journal article (peer-reviewed)abstract
- BACKGROUND.: To prepare a highly immunized recipient for heart transplantation, reduction of high levels of cytotoxic antibodies against human leukocyte antigen (HLA) was deemed essential to prevent antibody-mediated graft failure. METHODS.: Antibodies were analyzed by lymphocytotoxic and solid-phase assays. The pretransplant desensitization treatment protocol included daily tacrolimus and mycophenolate mofetil, weekly protein-A immunoadsorption (IA), intravenous immunoglobulin, and daclizumab. Posttransplant treatment consisted of tacrolimus, mycophenolate mofetil, prednisolone, IA, and daclizumab. RESULTS.: During pretransplant desensitization, each of the weekly immunoadsorption treatments reduced anti-HLA antibody levels by 50% to 70%, but they returned to the pretreatment level within 1 week as measured by flow cytometry. Cytotoxic antibodies remained reduced. After perioperative immunoadsorption, the donor-reactive antibodies (DRAs) were reduced to low levels. The patient underwent successful heart transplantation after 6 weeks on a waiting list. During the first week posttransplant, DRAs remained low. However, after the first week, anti-HLA DRAs reappeared and increased slightly over a 3-week period and then decreased slowly. Cytotoxic crossmatches were negative before and 3 week after transplantation. No clinical rejection was encountered. The patient was doing well 3 years after transplantation, and yearly clinical cardiac investigations were all normal. Three hyperimmunized patients have now undergone successful heart transplantation at our center using this desensitization protocol. CONCLUSIONS.: IA in combination with pretransplant immunosuppressive drug treatment temporarily reduces antibody levels. The therapeutic levels of drug treatment at the time of transplantation may be of crucial importance. The treatment protocol resulted in freedom from rejection and other clinical adverse events.
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- Gustafsson, Nils, et al.
(author)
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Associations among Periodontitis, Calcified Carotid Artery Atheromas, and Risk of Myocardial Infarction
- 2020
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In: Journal of Dental Research. - : Sage Publications. - 0022-0345 .- 1544-0591. ; 99:1, s. 60-68
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Journal article (peer-reviewed)abstract
- Cardiovascular disease is a common cause of morbidity and premature mortality. Cardiovascular disease can be prevented when risk factors are identified early. Calcified carotid artery atheromas (CCAAs), detected in panoramic radiographs, and periodontitis have both been associated with increased risk of cardiovascular disease. This case-control study aimed to 1) investigate associations between periodontitis and CCAA detected in panoramic radiographs and 2) determine the risk of future myocardial infarctions due to CCAA combined with periodontitis. We evaluated 1,482 participants (738 cases and 744 controls) with periodontitis and CCAAs recruited from the PAROKRANK study (Periodontitis and Its Relation to Coronary Artery Disease). Participants were examined with panoramic radiographs, including the carotid regions. Associations between myocardial infarction and periodontitis combined with CCAA were evaluated in 696 cases and 696 age-, sex-, and residential area-matched controls. Periodontitis was evaluated radiographically (as degree of bone loss) and with a clinical periodontal disease index score (from clinical and radiographic assessments). We found associations between CCAA and clinical periodontal disease index score among cases (odds ratio [OR], 1.51; 95% CI, 1.09 to 2.10; P = 0.02) and controls (OR, 1.70; 95% CI, 1.22 to 2.38; P < 0.01), although not between CCAA and the degree of bone loss. In a multivariable model, myocardial infarction was associated with CCAA combined with periodontitis, as assessed by degree of bone loss (OR, 1.75; 95% CI, 1.11 to 2.74; P = 0.01). When the cohort was stratified by sex, only men showed a significant association between myocardial infarction and CCAA combined with periodontitis. Participants with clinically diagnosed periodontitis exhibited CCAA in panoramic radiographs more often than those without periodontitis, irrespective of the presence of a recent myocardial infarction. Participants with combined periodontitis and CCAA had a higher risk of having had myocardial infarction as compared with participants with either condition alone. These findings implied that patients in dental care might benefit from dentists assessing panoramic radiographs for CCAA-particularly, patients with periodontitis who have not received any preventive measures for cardiovascular disease.
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- Hogberg, Göran, et al.
(author)
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Depressed adolescents in a case-series were low in vitamin D and depression was ameliorated by vitamin D supplementation
- 2012
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In: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 101:7, s. 779-783
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Journal article (peer-reviewed)abstract
- Aim: The relationship between depression in adolescents and vitamin D was studied in a case-series that included effects of vitamin D supplementation. Methods: Serum 25OH vitamin D (25OHD) levels in 54 Swedish depressed adolescents were investigated. Subjects with vitamin D deficiency were given vitamin D3 over 3 months (n = 48). To evaluate well-being and symptoms related to depression and vitamin D status, the WHO-5 well-being scale, the Mood and Feelings Questionnaire (MFQ-S) and a vitamin D deficiency scale were used. Results: Mean serum 25OHD in the depressed adolescents was 41 at baseline and 91 nmol/L (p < 0.001) after supplementation. Basal 25OHD levels correlated positively with well-being (p < 0.05). After vitamin D supplementation, well-being increased (p < 0.001) and there was a significant improvement in eight of the nine items in the vitamin D deficiency scale: depressed feeling (p < 0.001), irritability (p < 0.05), tiredness (p < 0.001), mood swings (p < 0.01), sleep difficulties (p < 0.01), weakness (p < 0.01), ability to concentrate (p < 0.05) and pain (p < 0.05). There was a significant amelioration of depression according to the MFQ-S (p < 0.05). Conclusion: This study showed low levels of vitamin D in 54 depressed adolescents, positive correlation between vitamin D and well-being, and improved symptoms related to depression and vitamin D deficiency after vitamin D supplementation.
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- Nyholm, Tufve, et al.
(author)
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A national approach for automated collection of standardized and population-based radiation therapy data in Sweden
- 2016
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In: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 119:2, s. 344-350
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Journal article (peer-reviewed)abstract
- Purpose: To develop an infrastructure for structured and automated collection of interoperable radiation therapy (RT) data into a national clinical quality registry. Materials and methods: The present study was initiated in 2012 with the participation of seven of the 15 hospital departments delivering RT in Sweden. A national RT nomenclature and a database for structured unified storage of RT data at each site (Medical Information Quality Archive, MIQA) have been developed. Aggregated data from the MIQA databases are sent to a national RT registry located on the same IT platform (INCA) as the national clinical cancer registries. Results: The suggested naming convention has to date been integrated into the clinical workflow at 12 of 15 sites, and MIQA is installed at six of these. Involvement of the remaining 3/15 RT departments is ongoing, and they are expected to be part of the infrastructure by 2016. RT data collection from ARIA (R), Mosaiq (R), Eclipse (TM), and Oncentra (R) is supported. Manual curation of RT-structure information is needed for approximately 10% of target volumes, but rarely for normal tissue structures, demonstrating a good compliance to the RT nomenclature. Aggregated dose/volume descriptors are calculated based on the information in MIQA and sent to INCA using a dedicated service (MIQA2INCA). Correct linkage of data for each patient to the clinical cancer registries on the INCA platform is assured by the unique Swedish personal identity number. Conclusions: An infrastructure for structured and automated prospective collection of syntactically inter operable RT data into a national clinical quality registry for RT data is under implementation. Future developments include adapting MIQA to other treatment modalities (e.g. proton therapy and brachytherapy) and finding strategies to harmonize structure delineations. How the RT registry should comply with domain-specific ontologies such as the Radiation Oncology Ontology (ROO) is under discussion.
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- Omstedt, Anders, 1949, et al.
(author)
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Future changes in the Baltic Sea acid-base (pH) and oxygen balances
- 2012
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In: Tellus. Series B, Chemical and physical meteorology. - : Stockholm University Press. - 0280-6509 .- 1600-0889. ; 64
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Journal article (peer-reviewed)abstract
- Possible future changes in Baltic Sea acid–base (pH) and oxygen balances were studied using a catchment–sea coupled model system and numerical experiments based on meteorological and hydrological forcing datasets and scenarios. By using objective statistical methods, climate runs for present climate conditions were examined and evaluated using Baltic Sea modelling. The results indicate that increased nutrient loads will not inhibit future Baltic Sea acidification; instead, the seasonal pH cycle will be amplified by increased biological production and mineralization. All examined scenarios indicate future acidification of the whole Baltic Sea that is insensitive to the chosen global climate model. The main factor controlling the direction and magnitude of future pH changes is atmospheric CO2 concentration (i.e. emissions). Climate change and land-derived changes (e.g. nutrient loads) affect acidification mainly by altering the seasonal cycle and deep-water conditions. Apart from decreasing pH, we also project a decreased saturation state of calcium carbonate, decreased respiration index, and increasing hypoxic area – all factors that will threaten the marine ecosystem. We demonstrate that substantial reductions in fossil-fuel burning are needed to minimize the coming pH decrease and substantial reductions in nutrient loads are needed to reduce the coming increase in hypoxic and anoxic waters.
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- Ragnarsdottir, Bryndis, et al.
(author)
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Toll-like receptor 4 promoter polymorphisms: common TLR4 variants may protect against severe urinary tract infection.
- 2010
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 5:5
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Journal article (peer-reviewed)abstract
- BACKGROUND: Polymorphisms affecting Toll-like receptor (TLR) structure appear to be rare, as would be expected due to their essential coordinator role in innate immunity. Here, we assess variation in TLR4 expression, rather than structure, as a mechanism to diversify innate immune responses. METHODOLOGY/PRINCIPAL FINDINGS: We sequenced the TLR4 promoter (4,3 kb) in Swedish blood donors. Since TLR4 plays a vital role in susceptibility to urinary tract infection (UTI), promoter sequences were obtained from children with mild or severe disease. We performed a case-control study of pediatric patients with asymptomatic bacteriuria (ABU) or those prone to recurrent acute pyelonephritis (APN). Promoter activity of the single SNPs or multiple allelic changes corresponding to the genotype patterns (GPs) was tested. We then conducted a replication study in an independent cohort of adult patients with a history of childhood APN. Last, in vivo effects of the different GPs were examined after therapeutic intravesical inoculation of 19 patients with Escherichia coli 83972. We identified in total eight TLR4 promoter sequence variants in the Swedish control population, forming 19 haplotypes and 29 genotype patterns, some with effects on promoter activity. Compared to symptomatic patients and healthy controls, ABU patients had fewer genotype patterns, and their promoter sequence variants reduced TLR4 expression in response to infection. The ABU associated GPs also reduced innate immune responses in patients who were subjected to therapeutic urinary E. coli tract inoculation. CONCLUSIONS: The results suggest that genetic variation in the TLR4 promoter may be an essential, largely overlooked mechanism to influence TLR4 expression and UTI susceptibility.
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- Rådegran, Göran, et al.
(author)
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Characteristics and survival of adult Swedish PAH and CTEPH patients 2000-2014
- 2016
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In: Scandinavian Cardiovascular Journal. - : Taylor & Francis. - 1401-7431 .- 1651-2006. ; 50:4, s. 243-250
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Journal article (peer-reviewed)abstract
- OBJECTIVES: The Swedish Pulmonary Arterial Hypertension Register (SPAHR) is an open continuous register, including pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) patients from 2000 and onwards. We hereby launch the first data from SPAHR, defining baseline characteristics and survival of Swedish PAH and CTEPH patients.DESIGN: Incident PAH and CTEPH patients 2008-2014 from all seven Swedish PAH-centres were specifically reviewed.RESULTS: There were 457 PAH (median age: 67 years, 64% female) and 183 CTEPH (median age: 70 years, 50% female) patients, whereof 77 and 81%, respectively, were in functional class III-IV at diagnosis. Systemic hypertension, diabetes, ischaemic heart disease and atrial fibrillation were common comorbidities, particularly in those >65 years. One-, 3- and 5-year survival was 85%, 71% and 59% for PAH patients. Corresponding numbers for CTEPH patients with versus without pulmonary endarterectomy were 96%, 89% and 86% versus 91%, 75% and 69%, respectively. In 2014, the incidence of IPAH/HPAH, associated PAH and CTEPH was 5, 3 and 2 per million inhabitants and year, and the prevalence was 25, 24 and 19 per million inhabitants.CONCLUSION: The majority of the PAH and CTEPH patients were diagnosed at age >65 years, in functional class III-IV, and exhibiting several comorbidities. PAH survival in SPAHR was similar to other registers.
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- Soerensen, Anne. L., et al.
(author)
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Eutrophication Increases Phytoplankton Methylmercury Concentrations in a Coastal Sea-A Baltic Sea Case Study
- 2016
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In: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 50:21, s. 11787-11796
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Journal article (peer-reviewed)abstract
- Eutrophication is expanding worldwide, but its implication for production and bioaccumulation of neurotoxic monomethylmercury (MeHg) is unknown. We developed a mercury (Hg) biogeochemical model for the Baltic Sea and used it to investigate the impact of eutrophication on phytoplankton MeHg concentrations. For model evaluation, we measured total methylated Hg (MeHgT) in the Baltic Sea and found low concentrations (39 +/- 16 fM) above the halocline and high concentrations in anoxic waters (1249 +/- 369 fM). To close the Baltic Sea MeHgT budget, we inferred an average normoxic water column HgII methylation rate constant of 2 x 10-4 d-1. We used the model to compare Baltic Seas present-day (2005-2014) eutrophic state to an oligo/mesotrophic scenario. Eutrophication increases primary production and export of organic matter and associated Hg to the sediment effectively removing Hg from the active biogeochemical cycle; this results in a 27% lower present-day water column Hg reservoir. However, increase in organic matter production and remineralization stimulates microbial Hg methylation resulting in a seasonal increase in both water and phytoplankton MeHg reservoirs above the halocline. Previous studies of systems dominated by external MeHg sources or benthic production found eutrophication to decrease MeHg levels in plankton. This Baltic Sea study shows that in systems with MeHg production in the normoxic water column eutrophication can increase phytoplankton MeHg content.
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