| 1. |
|
|
| 2. |
- Rosenqvist, Lars, et al.
(författare)
-
Spridning av högfluorerade ämnen i mark från Stockholm Arlanda Airport
- 2017
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Högfluorerade ämnen (PFAS) utgör en stor grupp syntetiska kemikalier som har tillverkats sedan 1950-talet för en mängd olika användningsområden i industriella processer och konsumentprodukter. Användningen av PFAS har dock ifrågasatts av forskare och myndigheter sedan början av 2000-talet då ett flertal av dessa ämnen har visats vara persistenta (ej nedbrytbara), bioackumulerande (anrikas i organismer) och toxiska (giftiga) i miljön. Ett av de mest uppmärksammade föroreningsproblemen med PFAS är den historiska användningen av filmbildande brandsläckningsskum (AFFF) som har lett till lokalt förhöjda halter av perfluoroktansulfonat (PFOS) i miljön runt brandövningsplatser. I denna rapport presenteras resultaten från projektet Re-PATH II som syftade till att studera spridningen av PFAS i mark, yt och grundvatten kring brandövningsplatsen på Stockholm Arlanda Airport (Arlanda flygplats). Fältundersökningar och provtagning har utförts i flera omgångar mellan september och november 2015. Jord, yt- och grundvattenprover analyserades för 13 PFAS och karakteriserades med avseende på organisk kol, mineralsammansättning, pH och konduktivitet. Tolkning av data utfördes med hjälp av multivariata statistiska metoder och en mekanistisk transportmodell. Detektionsfrekvensen av PFAS varierade mellan de olika provmatriserna, var i undersökningsområdet provet togs och de olika ämnenas kemiska struktur. PFAS-ämnen med upp till åtta perfluorerade kolatomer detekterades i stort sett i alla jord- och vattenprover medan de PFAS-ämnen med fler än åtta perfluorerade kolatomer endast återfanns i proverna nära källan. Halterna av samtliga PFAS uppvisade en exponentiellt minskande trend med ökande avstånd till källan vid brandövningsplatsen. En principalkomponentanalys visade signifikanta skillnader i kompositionen av olika PFAS i jord respektive vattenprover samt att dessa förändrades längs med provtagningsgradienten. Dessa trender i sammansättningen av olika PFAS kunde i sin tur förklaras av experimentellt bestämda fördelningskoefficienter från parade jord- och grundvattenprover. I överenstämmelse med tidigare studier observerades ett starkt positivt samband mellan Kd och antalet perfluorerade kolatomer (fluor bundet till kol). Simulerade och uppmätta koncentrationer av PFOS i grundvatten uppvisade relativt god överensstämmelse då platsspecifik inputdata användes. Transportmodellen underskattade dock halterna i grundvatten nära källtermen vilket indikerar att en linjär sorptionsmodell inte kan beskriva de komplexa interaktionerna mellan PFAS och jordmatrisen vid höga koncentrationer och förekomst av andra organiska föroreningar från brandövningsplatser. Med ledning av resultatet från denna studie bedöms grundvattnet inte vara en källa för långväga transport av PFOS och andra PFAS-ämnen med reservation för transport via sprickor i berggrunden som inte undersöktes här. Den främsta transportvägen av PFAS från brandövningsplatsen är istället via ytligt grundvatten, grunda dräneringsdiken eller lokala fördjupningar i terrängen. Baserat på dessa slutsatser skulle uppsamling och rening av dessa ytliga vattenflöden kunna utgöra en rimlig åtgärdsstrategi för att minska belastningen av PFAS till Mälaren.
|
|
| 3. |
- Svenungsson, Elisabet, et al.
(författare)
-
Antiphospholipid antibodies in patients with myocardial infarction with and without obstructive coronary arteries
- 2022
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 291:3, s. 327-337
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Recent studies demonstrate that prothrombotic antiphospholipid antibodies (aPL) are overrepresented in patients with myocardial infarction (MI) due to coronary artery disease (MICAD). However, it is not known whether aPL differ between the two subsets of MI: MICAD and MI with nonobstructive coronary arteries (MINOCA). Objectives: To determine whether aPL are associated with MINOCA or MICAD, or with hypercoagulability as assessed by activated protein C–protein C inhibitor (APC–PCI) complex. Methods: Well-characterized patients with MINOCA (n = 98), age- and gender-matched patients with MICAD (n = 99), and healthy controls (n = 100) were included in a cross-sectional case–control study. Autoantibodies (IgA/G/M) targeting cardiolipin and β2glycoprotein-I and specific nuclear antigens were analyzed by multiplexed bead technology. The concentration of APC–PCI was determined as a measure of hypercoagulability by an immunofluorometric sandwich assay. Results: Both prevalence and titers of aPL of the IgG isotype (anti-cardiolipin and/or anti-β2glycoprotein-I) were higher in patients with MINOCA and MICAD than in controls. aPL IgG positivity was twice as frequent among patients with MICAD than MINOCA (11% vs. 6%, nonsignificant). We observed no group differences regarding aPL IgA/M or antibodies targeting specific nuclear antigens. Levels of APC–PCI were elevated in aPL IgG-positive compared to aPL IgG-negative MICAD patients. Conclusions: aPL IgG, but not IgA/M, are enriched particularly in patients with MICAD but also in patients with MINOCA, as compared to controls. Interestingly, signs of hypercoagulability—measured by increased levels of the APC–PCI complex—were present in aPL IgG-positive MICAD patients, indicating an association with functional disturbances of the coagulation system.
|
|
| 4. |
- Ahmad, Abrar, et al.
(författare)
-
Evaluation of Expression Level of Apolipoprotein M as a Diagnostic Marker for Primary Venous Thromboembolism
- 2018
-
Ingår i: Clinical and Applied Thrombosis/Hemostasis. - : SAGE Publications. - 1938-2723 .- 1076-0296. ; 24:3, s. 416-422
-
Tidskriftsartikel (refereegranskat)abstract
- Recently, decreased levels of apolipoprotein M (ApoM) were shown to be associated with higher risk of recurrent venous thromboembolism (VTE) in male patients. However, the role of ApoM in primary VTE is unknown. We aimed in our study to analyze the plasma levels of ApoM in patients with VTE in order to evaluate the diagnostic importance of ApoM in primary VTE. A total of 357 patients with suspected first episode of VTE were recruited prospectively in the SCORE study. Plasma samples from 307 patients were available for quantifying the plasma levels of ApoM in patients with VTE using sandwich enzyme-linked immunosorbent assay method. Among the whole population, plasma levels (mean [standard deviation]) of ApoM were not significantly different between patients with VTE (0.72 [0.20]) and non-VTE patients (0.72 [0.16]), P = .99. Similarly, in regression analyses, no significant association of ApoM plasma levels with the risk of VTE was found on univariate (odds ratio [OR] =1.0, 95% confidence interval [CI] 0.21-4.84, P = .99) and multivariate analysis (OR = 1.25, 95% CI = 0.19-8.34, P = .819) after adjusting for age, body mass index, and smoking. Moreover, results did not differ significantly after stratification of data according to sex ( P > .05). In this study, our results do not suggest a diagnostic role for ApoM plasma levels in patients with primary VTE. Moreover, the current study suggests that role of ApoM as a risk factor may differ for primary VTE and recurrent VTE in male patients.
|
|
| 5. |
- Astermark, Jan, et al.
(författare)
-
Infrastructural considerations of implementing gene therapy for hemophilia in the Nordic context
- 2023
-
Ingår i: Therapeutic advances in hematology. - 2040-6207. ; 14
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Despite improvements in hemophilia care, challenges remain, including treatment burden and impaired quality of life. Gene therapy may overcome these. However, its introduction presents a challenge. Objectives: To outline a function-based gene therapy working model describing critical milestones associated with gene therapy handling, administration, and follow-up to facilitate and implement an effective infrastructure for gene therapy introduction. Design: Literature review and consensus discussion among Hemophilia Comprehensive Care centers (HCCCs) in the Nordic region. Methods: Representatives from six HCCCs sought to pinpoint milestones and key stakeholders for site readiness at the pre-, peri-, and post-infusion stages, including authority and genetically modified organism (GMO) product requirements, awareness, medical eligibility, logistics and product handling for infusion, laboratory monitoring, and follow-up. Results: A gene therapy transit map was developed with key stakeholders identified. The approach to prepare the vector will differ between the Nordic centers, but the contracted pharmacy unit will be a key stakeholder. Therefore, a pharmacy checklist for the implementation of gene therapy was developed. For the future, Advanced Therapy Medicinal Product centers will also be implemented. Patients’ expectations, commitments, and concerns need to be addressed repeatedly and education of patients and the expanded health-care professionals team will be the key to successful and optimal clinical management. Eligibility testing according to the product’s summary of product characteristics and frequent follow-up and monitoring post-infusion according to the World Federation of Hemophilia chart will be crucial. Conclusion: The approach to deliver gene therapy in the Nordic region will differ partly between the hemophilia centers, but the defined road map with checklists for the implementation of this advanced therapy will be applicable to all. The map may also serve as a platform for the use of future GMO product options both within and outside the area of hemophilia.
|
|
| 6. |
- Augustsson, Cecilia, et al.
(författare)
-
A nonneutralizing antibody as cause of prothrombin deficiency in a patient with follicular lymphoma
- 2024
-
Ingår i: Clinical Case Reports. - : WILEY. - 2050-0904. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Acquired inhibitors of blood coagulation are rare but of clinical importance. Prothrombin is a vitamin K-dependent protein, and acquired antibodies toward prothrombin are often associated with the presence of lupus anticoagulant. We describe a previously healthy 70-year-old man presenting with both hemorrhage and thrombosis as well as a prolonged prothrombin time. At arrival at the hospital, he was diagnosed with deep venous thrombosis, and an enlarged lymph node in the left groin was noted (revealed as follicular lymphoma grade 1 by biopsy). Prothrombin activity and antibody titer were followed for 5 months with 15 sampling time points to monitor the treatment outcome of the patient. Diagnostic work-up identified prothrombin deficiency as cause of bleeding. A nonneutralizing calcium-dependent antiprothrombin antibody was found, suspected to increase the clearance of prothrombin, which has previously only occasionally been reported. Lupus anticoagulant was ruled out and thrombosis was judged to be caused by a combination of malignant disease and stagnant venous flow following enlarged lymph nodes in the groin. This report illustrates how investigation of prolonged global coagulation tests, triggered the diagnosis of a rare but critical condition, immune-mediated prothrombin deficiency. The diagnosis is challenging and involves proper differential diagnosis. image
|
|
| 7. |
- Augustsson, Cecilia, et al.
(författare)
-
Validation of factor VIII activity for monitoring standard and extended half-life products and correlation to thrombin generation assays
- 2021
-
Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 27:3, s. 494-500
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Monitoring replacement therapy with standard and extended half-life (EHL) products is challenging, since one-stage assay (OSA) and chromogenic substrate assay (CSA) results may differ significantly. Recent recommendations include local validation of each new product with recovery within 20–30%, depending on activity level. Aim: To validate factor VIII (FVIII) activity for monitoring products in clinical use on Atellica Coag and to correlate it with thrombin generation. Methods: Plasma samples spiked with Advate®, Elocta®, Adynovi®, Nuwiq®, NovoEight® and Afstyla® (0.05, 0.20, 0.50 and 0.80 IU/ml) were analysed using Atellica Coag 360 with CSA-1 (Coatest SP) and CSA-2 (FVIII chromogenic), and OSA (Actin FS). Thrombin generation was performed using two thrombin generation assays (TGA-1 (Thrombinoscope) and TGA-2 (Technothrombin). Results: All products at levels above 0.05 IU/ml, except Adynovi, showed acceptable recovery using CSA-1, whereas measurements using CSA-2 gave more results outside the target level. All products, except Afstyla, showed acceptable recovery using OSA. Correlation between CSA-1 and OSA was excellent (r2=1.0) with biases of 6–32%, depending on FVIII product. A clear dose-response was seen for all thrombin generation parameters and products using both methods, except at low levels for lag time using TGA-1. With CSA-1 as an independent variable, the correlations to thrombin peak (measured with TGA-2) were good (r2 =.8–.9). Conclusion: Our data revealed good correlation and acceptable bias between CSA and OSA using our sets of reagents, methods and analyser in spiked samples. Thrombin generation gave good correlation to CSA-1 factor activity and is a possible complement to factor activity assays.
|
|
| 8. |
- Bakoush, Omran, et al.
(författare)
-
Low Plasma Activated Protein C-Protein C Inhibitor Complex Concentration Is Associated with Vascular Access Failure in Hemodialysis Patients.
- 2008
-
Ingår i: Nephron Clinical Practice. - : S. Karger AG. - 1660-2110. ; 110:3, s. 151-157
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Vascular access failure is a common cause of morbidity in patients with end-stage renal failure on hemodialysis (HD). Activation of the coagulation system and formation of a thrombus play important roles in recurrent arteriovenous fistula/graft (AVFG) failure. Thrombin in complex with thrombomodulin (TM) activates the anticoagulant protein C and creates activated protein C (APC), which is subsequently inactivated by the protein C inhibitor (PCI). The plasma concentration of the complex between APC and PCI (P-APC-PCI complex) is increased in hypercoagulable states and is therefore a sensitive indicator of the degree of activation of blood coagulation. Methods: Thirty-five HD patients dialyzed through a functioning AVFG were studied. The period of patency of AVFGs was recorded. Blood was drawn before and after the HD session for the analysis of the APC-PCI complex, soluble TM concentration and activity, von Willebrand factor antigen and homocysteine. Results: Patients with frequent AVFG failures (n = 8) had a significantly lower level of P-APC-PCI complex (median 0.09 mug/l) than those with less frequent AVFG failures (median 0.18 mug/l; n = 27; p = 0.04). No other significant differences were found between the groups. Conclusion: Thus, a low level of P-APC-PCI complex may be associated with an increased risk of AVFG failure in HD patients. Further prospective studies are needed to confirm these results and to evaluate the possibility of prophylactic measures.
|
|
| 9. |
- Bhiladvala, Pallonji, et al.
(författare)
-
Early identification of acute myocardial infarction by activated protein C-protein C inhibitor complex.
- 2006
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 118:Aug 10, s. 213-219
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Increased coagulation activity due to coronary thrombosis in a ruptured plaque should result in activation of the protein C anticoagulant system with formation of complexes between activated protein C (APC) and,the protein C inhibitor (PCI), which reflects coagulation activity. We hypothesized that elevated APC-PCI concentration might allow earlier detection of ongoing myocardial infarction than traditional biochemical markers. We have evaluated a newly devised immunofluorimetric assay for measuring plasma concentration of APC-PCI complexes among patients with suspected acute coronary syndrome. Materials and methods: Blood samples were taken from 340 patients (median 71 years, range 31-97) with suspected acute coronary syndrome at first presentation in the emergency department. Electrocardiogram was recorded and APC PCI, Troponin I and Creatine kinase-MB concentrations were repeatedly measured 3 times at 6 h interval. Results: The 74 patients who were eventually diagnosed with myocardial infarction had a higher median level of APC-PCI complex than those Without myocardial damage; 0.27 vs. 0.20 mu g/L (p = 0.001). In a multivariate regression model, APC-PCI level in the fourth quartile (> 0.32 mu g/L) independently predicted myocardial infarction with an odds ratio of 3.7 (95% CI 1.4-9.6, p < 0.01). Conclusion: Early APC-PCI elevation can be detected among patients with a normal first Troponin I and non-ST-elevation myocardial infarction and provides additional risk assessment in acute coronary syndrome. (c) 2005 Published by Elsevier Ltd.
|
|
| 10. |
- Bian, Li, et al.
(författare)
-
Rutinmässig screening med APTT är inte indicerad före operation : [Routine screening with APTT is not indicated before surgery
- 2022
-
Ingår i: Läkartidningen. - : Sveriges Läkarförbund. - 0023-7205 .- 1652-7518. ; 119
-
Forskningsöversikt (refereegranskat)abstract
- Activated partial thromboplastin time (APTT) is widely practiced in preoperative screening. The value of using this test to predict the risk of perioperative bleeding is not well documented in Sweden. In this article, a literature review is performed to determine whether unselected APTT testing can predict abnormal perioperative bleeding. The current literature does not support coagulation screening with APTT in routine perioperative bleeding assessment, as preoperative screening with APTT has a low sensitivity for detection of clinically significant bleeding disorder. While a comprehensive bleeding history is crucial, the APTT test should only be performed on patients with a history of increased bleeding tendency. The conclusion of this literature review is that patients with a negative bleeding history do not require routine screening with APTT prior to surgery, which, if implemented, would lead to a more cost-effective perioperative routine.
|
|
