| 41. |
- Stattin, Eva-Lena, et al.
(författare)
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A missense mutation in the aggrecan C-type lectin domain disrupts extracellular matrix interactions and causes dominant familial osteochondritis dissecans
- 2010
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 86:2, s. 126-137
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Tidskriftsartikel (refereegranskat)abstract
- Osteochondritis dissecans is a disorder in which fragments of articular cartilage and subchondral bone dislodge from the joint surface. We analyzed a five-generation family in which affected members had autosomal-dominant familial osteochondritis dissecans. A genome-wide linkage analysis identified aggrecan (ACAN) as a prime candidate gene for the disorder. Sequence analysis of ACAN revealed heterozygosity for a missense mutation (c.6907G > A) in affected individuals, resulting in a p.V2303M amino acid substitution in the aggrecan G3 domain C-type lectin, which mediates interactions with other proteins in the cartilage extracellular matrix. Binding studies with recombinant mutated and wild-type G3 proteins showed loss of fibulin-1, fibulin-2, and tenascin-R interactions for the V2303M protein. Mass spectrometric analyses of aggrecan purified from patient cartilage verified that V2303M aggrecan is produced and present in the tissue. Our results provide a molecular mechanism for the etiology of familial osteochondritis dissecans and show the importance of the aggrecan C-type lectin interactions for cartilage function in vivo.
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| 42. |
- Suserud, Björn-Ove, et al.
(författare)
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Caring for patients at high speed
- 2013
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Ingår i: Emergency Nurse. - : RCNI. - 1354-5752 .- 2047-8984. ; 21:7, s. 14-18
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The aim of this article is to explore whether ambulance clinicians in Sweden perceive their working environment to be safe. Method: Twenty four ambulance nurses and nine paramedics at five ambulance stations in urban and rural areas of Sweden were interviewed. Findings: After transcripts of the interviews had been analysed, nine issues that affect how participants perceive the safety of patient care in ambulances emerged: planning before departure; use of safety belts; driving at high speeds; patient first, safety second; equipment design and placement; noise; driving styles; presence of relatives; documentation. Conclusion: Ambulance personnel should have greater involvement in the design of ambulance care spaces and drivers should be given more regular training.
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| 43. |
- Sällman Almén, Markus, et al.
(författare)
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Shrunken Pore Syndrome Is Associated With Increased Levels of Atherosclerosis-Promoting Proteins
- 2019
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Ingår i: Kidney International Reports. - : Elsevier BV. - 2468-0249. ; 4:1, s. 67-79
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Shrunken pore syndrome (SPS), originally defined by cystatin C-based estimated glomerular filtration rate (eGFRcystatin C) being less than 60% of creatinine-based estimated glomerular filtration rate (eGFRcreatinine) in the absence of extrarenal influences on the plasma levels of cystatin C or creatinine, is associated with a high increase in mortality, even in the absence of reduced glomerular filtration rate (GFR). The objective of the present study was to determine whether the proteome of patients with SPS shows differences from that of patients with normal or reduced measured GFR (mGFR) without SPS.Methods: Four patient cohorts were included: 1 cohort with normal mGFR without SPS, 1 with normal mGFR with SPS, 1 with reduced mGFR without SPS, and 1 with reduced mGFR with SPS. The plasma levels of 177 selected proteins were analyzed.Results: Differences in the levels of 30 proteins were specific for SPS; 31 differences were specific for patients with both SPS and reduced mGFR; and 27 were specific for reduced mGFR. Eighteen of the differences specific for SPS concerned proteins described as promoting, or being associated with, atherosclerosis. Twelve of the differences specific for patients with both SPS and reduced mGFR and 10 of the differences specific for reduced mGFR also concerned proteins described as promoting, or being associated with, atherosclerosis. Almost all (82 of 88) of the concentration differences represented increased levels. For SPS, but not for reduced mGFR, a correlation between protein size and increase in level was observed, with smaller proteins being associated with higher levels.Conclusion: The high mortality in shrunken pore syndrome might be caused by the accumulation of atherosclerosis-promoting proteins in this condition.
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| 44. |
- Vukusic, Kristina, 1979, et al.
(författare)
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High Density Sphere Culture of Adult Cardiac Cells Increases the Levels of Cardiac and Progenitor Markers and Shows Signs of Vasculogenesis
- 2013
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Ingår i: Biomed Research International. - : Hindawi Limited. - 2314-6133 .- 2314-6141.
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Tidskriftsartikel (refereegranskat)abstract
- 3D environment and high cell density play an important role in restoring and supporting the phenotypes of cells represented in cardiac tissues.. e aim of this study was therefore to investigate the suitability of high density sphere (HDS) cultures for studies of cardiomyocyte-, endothelial-, and stem-cell biology. Primary adult cardiac cells from nine human biopsies were cultured using different media for up to 9 weeks.. e possibilities to favor a certain cell phenotype and induce production of extra cellular matrix (ECM) were studied by histology, immunohistochemistry, and uantitative real-time PCR. Defined media gave significant increase in both cardiac-and progenitor-specific markers and also an intraluminal position of endothelial cells over time. Cardiac media showed indication of differentiation and maturity of HDS considering the ECM production and activities within NOTCH regulation but no additional cardiac differentiation. Endothelial media gave no positive effects on endothelial phenotype but increased proliferation without fibroblast overgrowth. In addition, indications for early vasculogenesis were found. It was also possible to affect the Wnt signaling in HDS by addition of a glycogen synthase kinase 3 (GSK3) inhibitor. In conclusion, these findings show the suitability of HDS as in vitro model for studies of cardiomyocyte-, endothelial-, and stem-cell biology.
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| 45. |
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| 46. |
- Adjeiwaah, Mary, 1980-, et al.
(författare)
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Dosimetric Impact of MRI Distortions : A Study on Head and Neck Cancers
- 2019
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier. - 0360-3016 .- 1879-355X. ; 103:4, s. 994-1003
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To evaluate the effect of magnetic resonance (MR) imaging (MRI) geometric distortions on head and neck radiation therapy treatment planning (RTP) for an MRI-only RTP. We also assessed the potential benefits of patient-specific shimming to reduce the magnitude of MR distortions for a 3-T scanner.Methods and Materials: Using an in-house Matlab algorithm, shimming within entire imaging volumes and user-defined regions of interest were simulated. We deformed 21 patient computed tomography (CT) images with MR distortion fields (gradient nonlinearity and patient-induced susceptibility effects) to create distorted CT (dCT) images using bandwidths of 122 and 488 Hz/mm at 3 T. Field parameters from volumetric modulated arc therapy plans initially optimized on dCT data sets were transferred to CT data to compute a new plan. Both plans were compared to determine the impact of distortions on dose distributions.Results: Shimming across entire patient volumes decreased the percentage of voxels with distortions of more than 2 mm from 15.4% to 2.0%. Using the user-defined region of interest (ROI) shimming strategy, (here the Planning target volume (PTV) was the chosen ROI volume) led to increased geometric for volumes outside the PTV, as such voxels within the spinal cord with geometric shifts above 2 mm increased from 11.5% to 32.3%. The worst phantom-measured residual system distortions after 3-dimensional gradient nonlinearity correction within a radial distance of 200 mm from the isocenter was 2.17 mm. For all patients, voxels with distortion shifts of more than 2 mm resulting from patient-induced susceptibility effects were 15.4% and 0.0% using bandwidths of 122 Hz/mm and 488 Hz/mm at 3 T. Dose differences between dCT and CT treatment plans in D-50 at the planning target volume were 0.4% +/- 0.6% and 0.3% +/- 0.5% at 122 and 488 Hz/mm, respectively.Conclusions: The overall effect of MRI geometric distortions on data used for RTP was minimal. Shimming over entire imaging volumes decreased distortions, but user-defined subvolume shimming introduced significant errors in nearby organs and should probably be avoided.
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| 47. |
- Adjeiwaah, Mary, 1980-
(författare)
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Quality assurance for magnetic resonance imaging (MRI) in radiotherapy
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The use of Magnetic Resonance Imaging (MRI) in the radiotherapy (RT) treatment planning workflow is increasing. MRI offers superior soft-tissue contrast compared to Computed Tomography (CT) and therefore improves the accuracy in target volume definitions. There are, however concerns with inherent geometric distortions from system- (gradient nonlinearities and main magnetic field inhomogeneities) and patient-related sources (magnetic susceptibility effect and chemical shift). The lack of clearly defined quality assurance (QA) procedures has also raised questions on the ability of current QA protocols to detect common image quality degradations under radiotherapy settings. To fully implement and take advantage of the benefits of MRI in radiotherapy, these concerns need to be addressed.In Papers I and II, the dosimetric impact of MR distortions was investigated. Patient CTs (CT) were deformed with MR distortion vector fields (from the residual system distortions after correcting for gradient nonlinearities and patient-induced susceptibility distortions) to create distorted CT (dCT) images. Field parameters from volumetric modulated arc therapy (VMAT) treatment plans initially optimized on dCT data sets were transferred to CT data to compute new treatment plans. Data from 19 prostate and 21 head and neck patients were used for the treatment planning. The dCT and CT treatment plans were compared to determine the impact of distortions on dose distributions. No clinically relevant dose differences between distorted CT and original CT treatment plans were found. Mean dose differences were < 1.0% and < 0.5% at the planning target volume (PTV) for the head and neck, and prostate treatment plans, respectively. Strategies to reduce geometric distortions were also evaluated in Papers I and II. Using the vendor-supplied gradient non-linearity correction algorithm reduced overall distortions to less than half of the original value. A high acquisition bandwidth of 488 Hz/pixel (Paper I) and 488 Hz/mm (Paper II) kept the mean geometric distortions at the delineated structures below 1 mm. Furthermore, a patient-specific active shimming method implemented in Paper II significantly reduced the number of voxels with distortion shifts > 2 mm from 15.4% to 2.0%.B0 maps from patient-induced magnetic field inhomogeneities obtained through direct measurements and by simulations that used MR-generated synthetic CT (sCT) data were compared in Paper III. The validation showed excellent agreement between the simulated and measured B0 maps.In Paper IV, the ability of current QA methods to detect common MR image quality degradations under radiotherapy settings were investigated. By evaluating key image quality parameters, the QA protocols were found to be sensitive to some of the introduced degradations. However, image quality issues such as those caused by RF coil failures could not be adequately detected.In conclusion, this work has shown the feasibility of using MRI data for radiotherapy treatment planning as distortions resulted in a dose difference of less than 1% between distorted and undistorted images. The simulation software can be used to produce accurate B0 maps, which could then be used as the basis for the effective correction of patient-induced field inhomogeneity distortions and for the QA verification of sCT data. Furthermore, the analysis of the strengths and weaknesses in current QA tools for MRI in RT contribute to finding better methods to efficiently identify image quality errors.
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| 48. |
- Ahlgren, Göran M., et al.
(författare)
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Docetaxel Versus Surveillance After Radical Prostatectomy for High-risk Prostate Cancer : Results from the Prospective Randomised, Open-label Phase 3 Scandinavian Prostate Cancer Group 12 Trial
- 2018
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 73:6, s. 870-876
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Tidskriftsartikel (refereegranskat)abstract
- Background: Adjuvant chemotherapy is standard treatment for other solid tumours, but to date has not proven effective in prostate cancer. Objective: o evaluate whether six cycles of docetaxel alone improve biochemical disease-free survival after radical prostatectomy for high-risk prostate cancer. Design, setting, and participants: Open-label, randomised multinational phase 3 trial. Enrolment of 459 patients after prostatectomy. Inclusion criteria: high-risk pT2 margin positive or pT3a Gleason score ≥4+3, pT3b, or lymph node positive disease Gleason score ≥3+4. Patients assigned (1:1) to either six cycles of adjuvant docetaxel 75mg/m2 every 3 wk without daily prednisone (Arm A) or surveillance (Arm B) until endpoint was reached. Primary endpoint was prostate-specific antigen progression ≥0.5 ng/ml. Intervention: Docetaxel treatment after prostatectomy. Results and limitations: Median time to progression, death, or last follow-up was 56.8 mo. Primary endpoint was reached in 190/459 patients-the risk of progression at 5 yr being 41% (45% in Arm A and 38% in Arm B). There was evidence of nonproportional hazards in Kaplan-Meier analysis, so we used the difference in restricted mean survival time as the primary estimate of effect. Restricted mean survival time to endpoint was 43 mo in Arm A versus 46 mo in Arm B (p = 0.06), a nonsignificant difference of 3.2 mo (95% confidence interval: 6.7 to -1.5 mo). A total of 116 serious adverse events were recorded in Arm A and 41 in Arm B with no treatment-related deaths. Not all patients received docetaxel by protocol. The endpoint is biochemical progression and some patients received radiation treatment before the endpoint. Conclusions: Docetaxel without hormonal therapy did not significantly improve biochemical disease-free survival after radical prostatectomy. Patient summary: In this randomised trial, we tested whether chemotherapy after surgery for high-risk prostate cancer decreases the risk of a rising prostate-specific antigen. We found no benefit from docetaxel given after radical prostatectomy. In this randomised trial, docetaxel without hormonal therapy or continuous corticosteroids was given after radical prostatectomy for high-risk prostate cancer. We found no benefit from docetaxel alone given after radical prostatectomy.
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| 49. |
- Ahlsson, Fredrik, 1967-, et al.
(författare)
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Adipokines and their relation to maternal energy substrate production, insulin resistance and fetal size
- 2013
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Ingår i: European Journal of Obstetrics, Gynecology, and Reproductive Biology. - : Elsevier BV. - 0301-2115 .- 1872-7654. ; 168:1, s. 26-29
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:The role of adipokines in the regulation of energy substrate production in non-diabetic pregnant women has not been elucidated. We hypothesize that serum concentrations of adiponectin are related to fetal growth via maternal fat mass, insulin resistance and glucose production, and further, that serum levels of leptin are associated with lipolysis and that this also influences fetal growth. Hence, we investigated the relationship between adipokines, energy substrate production, insulin resistance, body composition and fetal weight in non-diabetic pregnant women in late gestation.STUDY DESIGN:Twenty pregnant women with normal glucose tolerance were investigated at 36 weeks of gestation at Uppsala University Hospital. Levels of adipokines were related to rates of glucose production and lipolysis, maternal body composition, insulin resistance, resting energy expenditure and estimated fetal weights. Rates of glucose production and lipolysis were estimated by stable isotope dilution technique.RESULTS:Median (range) rate of glucose production was 805 (653-1337)μmol/min and that of glycerol production, reflecting lipolysis, was 214 (110-576)μmol/min. HOMA insulin resistance averaged 1.5±0.75 and estimated fetal weights ranged between 2670 and 4175g (-0.2 to 2.7 SDS). Mean concentration of adiponectin was 7.2±2.5mg/L and median level of leptin was 47.1 (9.9-58.0)μg/L. Adiponectin concentrations (7.2±2.5mg/L) correlated inversely with maternal fat mass, insulin resistance, glucose production and fetal weight, r=-0.50, p<0.035, r=-0.77, p<0.001, r=-0.67, p<0.002, and r=-0.51, p<0.032, respectively. Leptin concentrations correlated with maternal fat mass and insulin resistance, r=0.76, p<0.001 and r=0.73, p<0.001, respectively. There was no correlation between maternal levels of leptin and rate of glucose production or fetal weight. Neither were any correlations found between levels of leptin or adiponectin and maternal lipolysis or resting energy expenditure.CONCLUSION:The inverse correlations between levels of maternal adiponectin and insulin resistance as well as endogenous glucose production rates indicate that low levels of adiponectin in obese pregnant women may represent one mechanism behind increased fetal size. Maternal levels of leptin are linked to maternal fat mass and its metabolic consequences, but the data indicate that leptin lacks a regulatory role with regard to maternal lipolysis in late pregnancy.
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| 50. |
- Ahlsson, Fredrik, et al.
(författare)
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Insulin Resistance, a Link between Maternal Overweight and Fetal Macrosomia in Nondiabetic Pregnancies
- 2010
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Ingår i: Hormone research in paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 74:4, s. 267-274
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: During the last decades the number of large for gestational age infants delivered by nondiabetic mothers has increased. Our aim was to investigate to what extent fetal growth in nondiabetic pregnant women can be explained by rates of maternal energy substrate production and resting energy expenditure. Methods: Twenty nonsmoking pregnant women without impaired glucose tolerance and with a wide range of fetal weights (0.2-2.7 SDS) were investigated at 36 weeks of gestation. Maternal lipolysis, glucose production, resting energy expenditure, body composition and insulin resistance were assessed.Results: Median (range) glucose production rate was 805 (653-1,337) mumol/min and that of glycerol, reflecting lipolysis, was 214 (110-576) mumol/min. Multiple linear regression analysis showed that maternal fat mass explained 36% of the variation in insulin resistance, accounting for 62% of the variation in glucose production. Further, glucose production explained 31% of the variation in fetal weight. Resting energy expenditure explained 51% of the variation in estimated fetal weight. Conclusion: Fetal weight is dependent on maternal glucose production, which is in turn determined by the degree of insulin resistance, induced in part by the maternal fat mass. The variation in maternal resting energy expenditure is closely related to fetal weight.
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