| 1. |
|
|
| 2. |
|
|
| 3. |
- Matic, L. P., et al.
(författare)
-
Novel Multiomics Profiling of Human Carotid Atherosclerotic Plaques and Plasma Reveals Biliverdin Reductase B as a Marker of Intraplaque Hemorrhage
- 2018
-
Ingår i: JACC: Basic to Translational Science. - : Elsevier BV. - 2452-302X. ; 3:4, s. 464-480
-
Tidskriftsartikel (refereegranskat)abstract
- Clinical tools to identify individuals with unstable atherosclerotic lesions are required to improve prevention of myocardial infarction and ischemic stroke. Here, a systems-based analysis of atherosclerotic plaques and plasma from patients undergoing carotid endarterectomy for stroke prevention was used to identify molecular signatures with a causal relationship to disease. Local plasma collected in the lesion proximity following clamping prior to arteriotomy was profiled together with matched peripheral plasma. This translational workflow identified biliverdin reductase B as a novel marker of intraplaque hemorrhage and unstable carotid atherosclerosis, which should be investigated as a potential predictive biomarker for cardiovascular events in larger cohorts.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Rykaczewska, U., et al.
(författare)
-
Plaque Evaluation by Ultrasound and Transcriptomics Reveals BCLAF1 as a Regulator of Smooth Muscle Cell Lipid Transdifferentiation in Atherosclerosis
- 2022
-
Ingår i: Arteriosclerosis Thrombosis and Vascular Biology. - : Ovid Technologies (Wolters Kluwer Health). - 1079-5642 .- 1524-4636. ; 42:5, s. 659-676
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Understanding the processes behind carotid plaque instability is necessary to develop methods for identification of patients and lesions with stroke risk. Here, we investigated molecular signatures in human plaques stratified by echogenicity as assessed by duplex ultrasound. Methods: Lesion echogenicity was correlated to microarray gene expression profiles from carotid endarterectomies (n=96). The findings were extended into studies of human and mouse atherosclerotic lesions in situ, followed by functional investigations in vitro in human carotid smooth muscle cells (SMCs). Results: Pathway analyses highlighted muscle differentiation, iron homeostasis, calcification, matrix organization, cell survival balance, and BCLAF1 (BCL2 [B-cell lymphoma 2]-associated transcription factor 1) as the most significant signatures. BCLAF1 was downregulated in echolucent plaques, positively correlated to proliferation and negatively to apoptosis. By immunohistochemistry, BCLAF1 was found in normal medial SMCs. It was repressed early during atherogenesis but reappeared in CD68+ cells in advanced plaques and interacted with BCL2 by proximity ligation assay. In cultured SMCs, BCLAF1 was induced by differentiation factors and mitogens and suppressed by macrophage-conditioned medium. BCLAF1 silencing led to downregulation of BCL2 and SMC markers, reduced proliferation, and increased apoptosis. Transdifferentiation of SMCs by oxLDL (oxidized low-denisty lipoprotein) was accompanied by upregulation of BCLAF1, CD36, and CD68, while oxLDL exposure with BCLAF1 silencing preserved MYH (myosin heavy chain) 11 expression and prevented transdifferentiation. BCLAF1 was associated with expression of cell differentiation, contractility, viability, and inflammatory genes, as well as the scavenger receptors CD36 and CD68. BCLAF1 expression in CD68+/BCL2+ cells of SMC origin was verified in plaques from MYH11 lineage-tracing atherosclerotic mice. Moreover, BCLAF1 downregulation associated with vulnerability parameters and cardiovascular risk in patients with carotid atherosclerosis. Conclusions: Plaque echogenicity correlated with enrichment of distinct molecular pathways and identified BCLAF1, previously not described in atherosclerosis, as the most significant gene. Functionally, BCLAF1 seems necessary for survival and transdifferentiation of SMCs into a macrophage-like phenotype. The role of BCLAF1 in plaque vulnerability should be further evaluated.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Chen, X., et al.
(författare)
-
A genome-wide association study of IgM antibody against phosphorylcholine: shared genetics and phenotypic relationship to chronic lymphocytic leukemia
- 2018
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 27:10, s. 1809-1818
-
Tidskriftsartikel (refereegranskat)abstract
- Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein (oxLDL), apoptotic cells and several pathogens like Streptococcus pneumoniae. Immunoglobulin M against PC (IgM anti-PC) has the ability to inhibit uptake of oxLDL by macrophages and increase clearance of apoptotic cells. From our genome-wide association studies (GWASs) in four European-ancestry cohorts, six single nucleotide polymorphisms (SNPs) in 11q24.1 were discovered (in 3002 individuals) and replicated (in 646 individuals) to be associated with serum level of IgM anti-PC (the leading SNP rs35923643-G, combined beta = 0.19, 95% confidence interval 0.13-0.24, P = 4.3 x 10-11). The haplotype tagged by rs35923643-G (or its proxy SNP rs735665-A) is also known as the top risk allele for chronic lymphocytic leukemia (CLL), and a main increasing allele for general IgM. By using summary GWAS results of IgM anti-PC and CLL in the polygenic risk score (PRS) analysis, PRS on the basis of IgM anti-PC risk alleles positively associated with CLL risk (explained 0.6% of CLL variance, P = 1.2 x 10-15). Functional prediction suggested that rs35923643-G might impede the binding of Runt-related transcription factor 3, a tumor suppressor playing a central role in the immune regulation of cancers. Contrary to the expectations from the shared genetics between IgM anti-PC and CLL, an inverse relationship at the phenotypic level was found in a nested case-control study (30 CLL cases with 90 age- and sex-matched controls), potentially reflecting reverse causation. The suggested function of the top variant as well as the phenotypic association between IgM anti-PC and CLL risk needs replication and motivates further studies.
|
|
| 13. |
|
|
| 14. |
- Daniel, M., et al.
(författare)
-
Prevalence of Anxiety and Depression Symptoms in Patients with Myocardial Infarction with Non-Obstructive Coronary Arteries
- 2018
-
Ingår i: American Journal of Medicine. - : Elsevier BV. - 0002-9343 .- 1555-7162. ; 131:9, s. 1118-1124
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Myocardial infarction with non-obstructive coronary arteries is a working diagnosis for several heart disorders. Previous studies on anxiety and depression in patients with myocardial infarction with non-obstructive coronary arteries are lacking. Our aim was to investigate the prevalence of anxiety and depression among patients with myocardial infarction with non-obstructive coronary arteries. METHODS: We included 99 patients with myocardial infarction with non-obstructive coronary arteries together with age- and sex-matched control groups who completed the Beck Depression Inventory and the Hospital Anxiety and Depression Scale (HADS) 3 months after the acute event. RESULTS: Using the Beck Depression Inventory, we found that the prevalence of depression in patients with myocardial infarction with non-obstructive coronary arteries (35%) was higher than in healthy controls (9%; P = .006) and similar to that of patients with coronary heart disease (30%; P = .954). Using the HADS anxiety subscale, we found that the prevalence of anxiety in patients with myocardial infarction with non-obstructive coronary arteries (27%) was higher than in healthy controls (9%; P = .002) and similar to that of patients with coronary heart disease (21%; P = .409). Using the HADS depression subscale, we found that the prevalence of depression in patients with myocardial infarction with non-obstructive coronary arteries (17%) was higher than in healthy controls (4%; P = .003) and similar to that of patients with coronary heart disease (13%; P = .466). Patients with myocardial infarction with non-obstructive coronary arteries and takotsubo syndrome scored higher on the HADS anxiety subscale than those without (P = .028). CONCLUSIONS: This is the first study on the mental health of patients with myocardial infarction with non obstructive coronary arteries to show that prevalence rates of anxiety and depression are similar to those in patients with coronary heart disease. (C) 2018 Elsevier Inc. All rights reserved.
|
|
| 15. |
|
|
| 16. |
- Eriksson, SV, et al.
(författare)
-
Diastolic and systolic function as predictors of exercise capacity after myocardial infarction in young Men
- 1998
-
Ingår i: Cardiology. - : S. Karger AG. - 0008-6312 .- 1421-9751. ; 90:1, s. 8-12
-
Tidskriftsartikel (refereegranskat)abstract
- We evaluated the power of measurements of left ventricular (LV) systolic and diastolic function for predicting exercise capacity in 97 young male survivors of a myocardial infarction. The patients were evaluated with M-mode echocardiography, a symptom-limited exercise test and coronary and LV angiography. In univariate analyses, maximum exercise workload was most closely related to the atrial emptying index, an index of diastolic function (r = 0.37, p < 0.005), but not to LV ejection fraction (r = 0.001, NS). This relationship was stronger in the 42 patients without signs of ischemia during exercise (r = 0.51, p < 0.005). Multivariate analyses indicated that the atrial emptying index (p < 0.005) provided independent contribution to the prediction of maximum exercise capacity. LV diastolic function but not LV systolic function was related to exercise capacity in young survivors of myocardial infarction.
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
- Ahlman, Håkan, 1947, et al.
(författare)
-
Management of disseminated midgut carcinoid tumours.
- 1991
-
Ingår i: Digestion. - 0012-2823. ; 49:2, s. 78-96
-
Tidskriftsartikel (refereegranskat)abstract
- Forty-one patients with disseminated midgut carcinoid tumours were treated over a 6-year period according to a strict programme including primary surgical treatment. In 10 patients, a total remission of the disease was obtained. Patients with bilobar hepatic disease had ischaemic treatment of their liver metastases by hepatic arterial embolisation after primary surgical and medical treatment (low dose octreotide). Thus, by combining surgical, radiological and medical treatment modalities, we wanted to offer these patients optimal palliation. This treatment programme resulted in good symptomatic relief in all patients accompanied by a marked reduction in 5-hydroxyindoleacetic acid (5-HIAA) levels. At recurrence of symptoms in combination with rising 5-HIAA levels, embolisation was repeated. Ten of the treated patients have deceased during the observation period, but only 5 from their carcinoid disease.
|
|
| 32. |
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
|
|
| 36. |
|
|
| 37. |
- Barrefelt, Asa, et al.
(författare)
-
Fluorescence labeled microbubbles for multimodal imaging
- 2015
-
Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 464:3, s. 737-742
-
Tidskriftsartikel (refereegranskat)abstract
- Air-filled polyvinyl alcohol microbubbles (PVA-MBs) were recently introduced as a contrast agent for ultrasound imaging. In the present study, we explore the possibility of extending their application in multimodal imaging by labeling them with a near infrared (NIR) fluorophore, VivoTag-680. PVA-MBs were injected intravenously into FVB/N female mice and their dynamic biodistribution over 24 h was determined by 3D-fluorescence imaging co-registered with 3D-mu CT imaging, to verify the anatomic location. To further confirm the biodistribution results from in vivo imaging, organs were removed and examined histologically using bright field and fluorescence microscopy. Fluorescence imaging detected PVA-MB accumulation in the lungs within the first 30 min post-injection. Redistribution to a low extent was observed in liver and kidneys at 4 h, and to a high extent mainly in the liver and spleen at 24 h. Histology confirmed PVA-MB localization in lung capillaries and macrophages. In the liver, they were associated with Kupffer cells; in the spleen, they were located mostly within the marginal-zone. Occasional MBs were observed in the kidney glomeruli and interstitium. The potential application of PVA-MBs as a contrast agent was also studied using ultrasound (US) imaging in subcutaneous and orthotopic pancreatic cancer mouse models, to visualize blood flow within the tumor mass. In conclusion, this study showed that PVA-MBs are useful as a contrast agent for multimodal imaging. (C) 2015 Elsevier Inc. All rights reserved.
|
|
| 38. |
|
|
| 39. |
|
|
| 40. |
- Bech-Hanssen, O, et al.
(författare)
-
Aortic prosthetic valve design and size : Relation to Doppler echocardiographic findings and pressure recovery - An in vitro study
- 2000
-
Ingår i: Journal of the American Society of Echocardiography. - 0894-7317 .- 1097-6795. ; 13:1, s. 39-50
-
Tidskriftsartikel (refereegranskat)abstract
- The extent to which Doppler echocardiography information can be used in the assessment of prosthesis hemodynamic performance is still controversial. The goals of our study were to assess the importance of valve design and size both on Doppler echocardiography findings and on pressure recovery in a fluid mechanics model. We performed Doppler and catheter measurements in the different orifices of the bileaflet St Jude (central and side orifices), the monoleaflet Omnicarbon (major and minor orifices), and the stented Biocor porcine prosthesis. Net pressure gradients were predicted from Doppler flow velocities, assuming either independence or dependence of valve size. The peak Doppler estimated gradients (mean +/- SD for sizes 21 to 27) were 21 +/- 10.3 rum Hg for St Jude, 18 +/- 9.3 mm Hg for Omnicarbon, and 37 +/- 14.5 mm Hg for Biocor (P <.05 for St Jude and Omnicarbon vs Biocor). The pressure recovery (proportion of peak catheter pressure) was 53% +/- 8.6% for central-St Jude, 29% +/- 8.9% for side-St Jude, 20% +/- 5.6% for major-Omnicarbon, 23% +/- 7.4% for minor-Omnicarbon, and 18% +/- 3.6% for Biocor (P <.05 for central-St Jude and side-St Jude vs Omnicarbon and Biocor). Valve sizes (2) significantly influenced pressure recovery (y in percentage) (central-St Jude: y = 3.7x - 35.9, r = 0.88, P =.0001, major-Omnicarbon: y = 2.1x - 30.3, r = 0.85, P =.0001). By assuming dependence of valve size, Doppler was able to predict net pressure gradients in St Jude with a mean difference between net catheter and Doppler-predicted gradient of - 3.8 +/- 2.5 mm Hg. In conclusion, prosthetic value design and size influence the degree of pressure recovery, making Doppler gradients potentially misleading in both the assessment of hemodynamic performance and the comparison of one design with another. The preliminary results indicate that net gradient can be predicted from Doppler gradients,
|
|
| 41. |
- Bech-Hanssen, O., et al.
(författare)
-
Net Pressure Gradients in Aortic Prosthetic Valves can be Estimated by Doppler
- 2003
-
Ingår i: Journal of the American Society of Echocardiography. - 0894-7317 .- 1097-6795. ; 16:8, s. 858-866
-
Tidskriftsartikel (refereegranskat)abstract
- Background: In aortic prosthetic valves, both the Doppler-estimated gradients and orifice areas are misleading in the assessment of hemodynamic performance. The parameter of major interest is the net pressure gradient after pressure recovery (PR). We, therefore, investigated, in vitro, our ability to predict the net pressure gradient and applied the formulas in a representative patient population with 2 different valve designs. Methods: We studied the St Jude Medical (SJM) standard valve (size 19-27) and SJM Biocor (size 21-27) in an in vitro steady-flow model with simultaneous Doppler-estimated pressure and catheter pressure measurements. Using echocardiography, we also studied patients who received the SJM (n = 66) and SJM Biocor (n = 45). Results: In the SJM, we observed PR both within the prosthesis and aorta, whereas in the SJM Biocor, PR was only present in the aorta. We estimated the PR within the valve and within the aorta separately from echocardiographic in vitro data, combining a regression equation (valve) with an equation on the basis of fluid mechanics theory (aorta). The difference between estimated and catheter-obtained net gradients (mean ± SD) was 0.6 ± 1.6 mm Hg in the SJM and - 0.2 ± 1.9 mm Hg in the SJM Biocor. When these equations were applied in vivo, we found that PR had an overall value of 57 ± 7% of the peak Doppler gradient in the SJM and 33 ± 9% in the SJM Biocor. Conclusions: The in vitro results indicate that it is possible to predict the net pressure gradient by Doppler in bileaflet and stented biologic valves. Our data indicate that important PR is also present in stented biologic valves.
|
|
| 42. |
|
|
| 43. |
- Berg, S, et al.
(författare)
-
A multi-pulse ultrasound technique for imaging of thick-shelled microbubbles demonstrated in vitro and in vivo
- 2022
-
Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:11, s. e0276292-
-
Tidskriftsartikel (refereegranskat)abstract
- Contrast enhanced ultrasound is a powerful diagnostic tool and ultrasound contrast media are based on microbubbles (MBs). The use of MBs in drug delivery applications and molecular imaging is a relatively new field of research which has gained significant interest during the last decade. MBs available for clinical use are fragile with short circulation half-lives due to the use of a thin encapsulating shell for stabilization of the gas core. Thick-shelled MBs can have improved circulation half-lives, incorporate larger amounts of drugs for enhanced drug delivery or facilitate targeting for use in molecular ultrasound imaging. However, methods for robust imaging of thick-shelled MBs are currently not available. We propose a simple multi-pulse imaging technique which is able to visualize thick-shelled polymeric MBs with a superior contrast-to-tissue ratio (CTR) compared to commercially available harmonic techniques. The method is implemented on a high-end ultrasound scanner and in-vitro imaging in a tissue mimicking flow phantom results in a CTR of up to 23 dB. A proof-of-concept study of molecular ultrasound imaging in a soft tissue inflammation model in rabbit is then presented where the new imaging technique showed an enhanced accumulation of targeted MBs in the inflamed tissue region compared to non-targeted MBs and a mean CTR of 13.3 dB for stationary MBs. The presence of fluorescently labelled MBs was verified by confocal microscopy imaging of tissue sections post-mortem.
|
|
| 44. |
|
|
| 45. |
- Blomström-Lundqvist, C, et al.
(författare)
-
Electrocardiographic findings and frequency of arrhythmias in Bartter's syndrome
- 1989
-
Ingår i: British Heart Journal. - 0007-0769. ; 61:3, s. 274-279
-
Tidskriftsartikel (refereegranskat)abstract
- Twenty four hour electrocardiograms in 20 patients with Bartter's syndrome, a disorder associated with chronic potassium deficiency, were analysed for atrial and ventricular extrasystoles, pauses (RR interval greater than 2 s), and heart rate. The 12 lead resting electrocardiogram was also evaluated. There were slight electrocardiographic changes with ST segment depression (greater than or equal to - 0.5 mm) in seven patients, flat or low amplitude T waves in seven, and U waves (greater than or equal to + 1.0 mm) in three patients. The QT interval was prolonged in 18 patients. Nine patients had one or more ventricular extrasystoles in 24 hours. Only two patients had more than 200 ventricular extrasystoles in 24 hours. No patient had ventricular tachycardia. A total of nine patients had one or more atrial extrasystoles in 24 hours, but only one patient had more than 200 in 24 hours. One patient had an attack of non-sustained supraventricular tachycardia. No patient had pauses. Dangerous tachycardia was rare in these patients with chronic potassium deficiency caused by Bartter's syndrome. The general pattern of slight electrocardiographic changes may reflect an adaptation of the myocardium to hypokalaemia. Further studies are, however, needed to determine whether these findings are relevant to long term prognosis.
|
|
| 46. |
- Brandrup-Wognsen, G, et al.
(författare)
-
Predictors for recurrent chest pain and relationship to myocardial ischaemia during long-term follow-up after coronary artery bypass grafting
- 1997
-
Ingår i: European Journal of Cardio-Thoracic Surgery. - : Elsevier BV. - 1010-7940 .- 1873-734X. ; 12:2, s. 304-311
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe the impact of coronary artery bypass grafting on chest pain during 2 years of follow-up after the operation and to identify predictors of chest pain and its relationship to myocardial ischaemia 2 years after the operation. Methods: Patients were approached with a questionnaire at the time of coronary angiography (1291) and 3 months (1664), 1 year (1638) and 2 years (1613) after coronary artery bypass grafting. Two years after the operation, a computerised 12-lead electrocardiogram was obtained during a standardised bicycle exercise test (618). Results: Prior to surgery, 37% of the patients were unable to perform physical activity compared with 6% after the operation (PB0.0001 for change in degree of limitation). Only 3% had no chest pain at all prior to the operation, while 58% of the patients were free from chest pain 2 years after surgery (PB0.0001). We found no correlation between patients reporting chest pain and signs of ischaemia at exercise test, but there was a highly significant correlation with chest pain during the exercise test (PB0.0001). Independent predictors of chest pain were severity of preoperative angina (PB0.0001), younger age (P 0.0009), previous coronary artery bypass grafting (P 0.003), duration of symptoms (P 0.005), the need for prolonged cardiopulmonary bypass (P 0.04) and the absence of left main stenosis (P 0.04). Conclusion: Independent predictors of chest pain were identified 2 years after coronary artery bypass grafting. There was a dramatic improvement after coronary artery bypass grafting. However, almost half the patients complained of some kind of chest pain even after the operation. This chest pain correlated well with chest pain during the exercise test but not with signs of myocardial ischaemia.
|
|
| 47. |
- Caidahl, Kenneth, 1949, et al.
(författare)
-
IgM-phosphorylcholine autoantibodies and outcome in acute coronary syndromes.
- 2012
-
Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 167:2, s. 464-469
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract BACKGROUND: Antibodies against proinflammatory phosphorylcholine (anti-PC) seem to be protective and reduce morbidity. We sought to determine whether low levels of immunoglobulin-M (IgM) autoantibodies against PC add prognostic information in acute coronary syndromes (ACS). METHODS: IgM anti-PC titers were measured in serum obtained within 24h of admission from 1185 ACS patients (median age 66years, 30% women). We evaluated major acute cardiovascular events (MACE) and all-cause mortality short- (6months), intermediate- (18months) and long- (72months) terms. RESULTS: Low anti-PC titers were associated with MACE and all-cause mortality at all follow-up times. After adjusting for clinical variables, plasma troponin-I, proBNP and CRP levels, associations remained at all times with MACE, short and intermediate terms also with all-cause mortality. With anti-PC titers below median, adjusted hazard ratios at 18months were for MACE 1.79 (95% confidence interval [CI]: 1.31 to 2.44; p=0.0002) and for all-cause mortality 2.28 (95% CI: 1.32 to 3.92; p=0.003). Anti-PC and plasma CRP were unrelated and added to risk prediction. CONCLUSIONS: Serum IgM anti-PC titers provide prognostic information above traditional risk factors in ACS. The ease of measurement and potential therapeutic perspective indicate that it may be a valuable novel biomarker in ACS.
|
|
| 48. |
- Caidahl, K, et al.
(författare)
-
Osteoprotegerin: a biomarker with many faces
- 2010
-
Ingår i: Arteriosclerosis, thrombosis, and vascular biology. - 1524-4636. ; 30:9, s. 1684-1686
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 49. |
|
|
| 50. |
|
|
