| 1. |
- Elhai, M, et al.
(författare)
-
Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study
- 2019
-
Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:7, s. 979-987
-
Tidskriftsartikel (refereegranskat)abstract
- To assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice.MethodsWe performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab.Results254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47–5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55–1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56–3.53], p<0.0001). Patients treated concomitantly with mycophenolate mofetil had a trend for better outcomes as compared with patients receiving rituximab alone (delta FVC: 5.22 [0.83–9.62]; p=0.019 as compared with controls vs 3 [0.66–5.35]; p=0.012).ConclusionRituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial.
|
|
| 2. |
|
|
| 3. |
- Becker, M, et al.
(författare)
-
Predictors of disease worsening defined by progression of organ damage in diffuse systemic sclerosis: a European Scleroderma Trials and Research (EUSTAR) analysis
- 2019
-
Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:9, s. 1242-1248
-
Tidskriftsartikel (refereegranskat)abstract
- Mortality and worsening of organ function are desirable endpoints for clinical trials in systemic sclerosis (SSc). The aim of this study was to identify factors that allow enrichment of patients with these endpoints, in a population of patients from the European Scleroderma Trials and Research group database.MethodsInclusion criteria were diagnosis of diffuse SSc and follow-up over 12±3 months. Disease worsening/organ progression was fulfilled if any of the following events occurred: new renal crisis; decrease of lung or heart function; new echocardiography-suspected pulmonary hypertension or death. In total, 42 clinical parameters were chosen as predictors for the analysis by using (1) imputation of missing data on the basis of multivariate imputation and (2) least absolute shrinkage and selection operator regression.ResultsOf 1451 patients meeting the inclusion criteria, 706 had complete data on outcome parameters and were included in the analysis. Of the 42 outcome predictors, eight remained in the final regression model. There was substantial evidence for a strong association between disease progression and age, active digital ulcer (DU), lung fibrosis, muscle weakness and elevated C-reactive protein (CRP) level. Active DU, CRP elevation, lung fibrosis and muscle weakness were also associated with a significantly shorter time to disease progression. A bootstrap validation step with 10 000 repetitions successfully validated the model.ConclusionsThe use of the predictive factors presented here could enable cohort enrichment with patients at risk for overall disease worsening in SSc clinical trials.
|
|
| 4. |
|
|
| 5. |
- Fransen, J., et al.
(författare)
-
Clinical prediction of 5-year survival in systemic sclerosis: validation of a simple prognostic model in EUSTAR centres
- 2011
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:10, s. 1788-1792
-
Tidskriftsartikel (refereegranskat)abstract
- Objective Systemic sclerosis (SSc) is associated with a significant reduction in life expectancy. A simple prognostic model to predict 5-year survival in SSc was developed in 1999 in 280 patients, but it has not been validated in other patients. The predictions of a prognostic model are usually less accurate in other patients, especially from other centres or countries. A study was undertaken to validate the prognostic model to predict 5-year survival in SSc in other centres throughout Europe. Methods A European multicentre cohort of patients with SSc diagnosed before 2002 was established. Patients with SSc according to the preliminary American College of Rheumatology classification criteria were eligible for the study when they were followed for at least 5 years or shorter if they died. The primary outcome was 5-year survival after diagnosis of SSc. The predefined prognostic model uses the following baseline variables: age, gender, presence of urine protein, erythrocyte sedimentation rate (ESR) and carbon monoxide diffusing capacity (DLCO). Results Data were available for 1049 patients, 119 (11%) of whom died within 5 years after diagnosis. Of the patients, 85% were female, the mean (SD) age at diagnosis was 50 (14) years and 30% were classified as having diffuse cutaneous SSc. The prognostic model with age (OR 1.03), male gender (OR 1.93), urine protein (OR 2.29), elevated ESR (1.89) and low DLCO (OR 1.94) had an area under the receiver operating characteristic curve of 0.78. Death occurred in 12 (2.2%) of 509 patients with no risk factors, 45 (13%) of 349 patients with one risk factor, 55 (33%) of 168 patients with two risk factors and 7 (30%) of 23 patients with three risk factors. Conclusion A simple prognostic model using three disease factors to predict 5-year survival at diagnosis in SSc showed reasonable performance upon validation in a European multicentre study.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Sarigul, Buse, et al.
(författare)
-
Prognostication and Goals of Care Decisions in Severe Traumatic Brain Injury : A Survey of The Seattle International Severe Traumatic Brain Injury Consensus Conference Working Group
- 2023
-
Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 40:15-16, s. 1707-1717
-
Tidskriftsartikel (refereegranskat)abstract
- Best practice guidelines have advanced severe traumatic brain injury (TBI) care; however, there is little that currently informs goals of care decisions and processes despite their importance and frequency. Panelists from the Seattle International severe traumatic Brain Injury Consensus Conference (SIBICC) participated in a survey consisting of 24 questions. Questions queried use of prognostic calculators, variability in and responsibility for goals of care decisions, and acceptability of neurological outcomes, as well as putative means of improving decisions that might limit care. A total of 97.6% of the 42 SIBICC panelists completed the survey. Responses to most questions were highly variable. Overall, panelists reported infrequent use of prognostic calculators, and observed variability in patient prognostication and goals of care decisions. They felt that it would be beneficial for physicians to improve consensus on what constitutes an acceptable neurological outcome as well as what chance of achieving that outcome is acceptable. Panelists felt that the public should help to define what constitutes a good outcome and expressed some support for a "nihilism guard." More than 50% of panelists felt that if it was certain to be permanent, a vegetative state or lower severe disability would justify a withdrawal of care decision, whereas 15% felt that upper severe disability justified such a decision. Whether conceptualizing an ideal or existing prognostic calculator to predict death or an unacceptable outcome, on average a 64-69% chance of a poor outcome was felt to justify treatment withdrawal. These results demonstrate important variability in goals of care decision making and a desire to reduce this variability. Our panel of recognized TBI experts opined on the neurological outcomes and chances of those outcomes that might prompt consideration of care withdrawal; however, imprecision of prognostication and existing prognostication tools is a significant impediment to standardizing the approach to care-limiting decisions.
|
|
| 10. |
|
|
| 11. |
- Sjoqvist, S, et al.
(författare)
-
Publisher Correction: Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats
- 2018
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9, s. 16208-
-
Tidskriftsartikel (refereegranskat)abstract
- Nature Communications 5: Article number: 3562 (2014); Published online: 15 April 2014; Updated: 10 April 2018 The original HTML version of this Article had an incorrect article number of 4562; it should have been 3562. This has now been corrected in the HTML; the PDF version of the Article was correct from the time of publication.
|
|
| 12. |
- Sjoqvist, S, et al.
(författare)
-
Retraction: Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats
- 2017
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8, s. 15077-
-
Tidskriftsartikel (refereegranskat)abstract
- Nature Communications 5: Article number: 3562 (2014); Published 15 April 2014; Updated 21 March 2017 This Article is retracted by the authors. Nature Communications previously issued an Editorial Expression of Concern (http://www.nature.com/articles/ncomms13310) related to this Article, following the publication of a report commissioned by The Karolinska Institute and prepared by the Expert Group for Misconduct in Research at the Swedish Central Ethical Review Board.
|
|
| 13. |
|
|
| 14. |
- Wigington, Callie P., et al.
(författare)
-
Systematic Discovery of Short Linear Motifs Decodes Calcineurin Phosphatase Signaling
- 2020
-
Ingår i: Molecular Cell. - : Cell Press. - 1097-2765 .- 1097-4164. ; 79:2, s. 342-
-
Tidskriftsartikel (refereegranskat)abstract
- Short linear motifs (SLiMs) drive dynamic protein-protein interactions essential for signaling, but sequence degeneracy and low binding affinities make them difficult to identify. We harnessed unbiased systematic approaches for SLiM discovery to elucidate the regulatory network of calcineurin (CN)/PP2B, the Ca 2+-activated phosphatase that recognizes LxVP and PxIxIT motifs. In vitro proteome-wide detection of CN-binding peptides, in vivo SLiM-dependent proximity labeling, and in silico modeling of motif determinants uncovered unanticipated CN interactors, including NOTCH1, which we establish as a CN substrate. Unexpectedly, CN shows SLiM-dependent proximity to centrosomal and nuclear pore complex (NPC) proteins—structures where Ca 2+ signaling is largely uncharacterized. CN dephosphorylates human and yeast NPC proteins and promotes accumulation of a nuclear transport reporter, suggesting conserved NPC regulation by CN. The CN network assembled here provides a resource to investigate Ca 2+ and CN signaling and demonstrates synergy between experimental and computational methods, establishing a blueprint for examining SLiM-based networks.
|
|
| 15. |
|
|
| 16. |
- Andersson, F, et al.
(författare)
-
Adding formoterol to budesonide in moderate asthma--health economic results from the FACET study
- 2001
-
Ingår i: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 95:6, s. 505-512
-
Tidskriftsartikel (refereegranskat)abstract
- The FACET (Formoterol and Corticosteroid Establishing Therapy) study established that there is a clear clinical benefit in adding formoterol to budesonide therapy in patients who have persistent symptoms of asthma despite treatment with low to moderate doses of an inhaled corticosteroid. We combined the clinical results from the FACET study with an expert survey on average resource use in connection with mild and severe asthma exacerbations in the U.K., Sweden and Spain. The primary objective of this study was to assess the health economics of adding the inhaled long-acting beta2-agonist formoterol to the inhaled corticosteroid budesonide in the treatment of asthma. The extra costs of adding the inhaled beta2-agonist formoterol to the corticosteroid budesonide in asthmatic patients in Sweden were offset by savings from reduced use of resources for exacerbations. For Spain the picture was mixed. Adding formoterol to low dose budesonide generated savings, whereas for moderate doses of budesonide about 75% of the extra formoterol costs could be recouped. In the U.K., other savings offset about half of the extra cost of formoterol. All cost-effectiveness ratios are within accepted cost-effectiveness ranges reported from previous studies. If productivity losses were included, there were net savings in all three countries, ranging from Euro 267-1183 per patient per year. In conclusion, adding the inhaled, long-acting beta2-agonist formoterol to low-moderate doses of the inhaled corticosteroid budesonide generated significant gains in all outcome measures with partial or complete offset of costs. Adding formoterol to budesonide can thus be considered to be cost-effective.
|
|
| 17. |
- Barsoe, S, et al.
(författare)
-
RT-qPCR assay for detection of mink astrovirus in outbreaks of diarrhea on Danish mink farms
- 2021
-
Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 16:5, s. e0252022-
-
Tidskriftsartikel (refereegranskat)abstract
- Diarrhea in mink kits is a major cause of disease and mortality in the mink production. The etiology remains unknown in most outbreaks due to a lack of diagnostic assays. In the current study we present an RT-qPCR method to detect mink astrovirus in fecal samples from mink kits with diarrhea. All sampled animals were classified based on age and patoanatomical evaluation as having pre-weaning diarrhea, diarrhea in the growth period or as having no macroscopic signs of diarrhea. Fecal samples were analyzed for MiAstV with RT-qPCR, next generation sequencing and electron microscopy in parallel. Mink astrovirus was detected with RT-qPCR in 92 out of 203 samples. This detection was confirmed by next generation sequencing in a high proportion of samples (22/27), and by visualization of astrovirus particles with EM in some of the samples. Mink astrovirus was highly prevalent (68%) among kits in the outbreaks of pre-weaning diarrhea, in particular outbreaks from May, while less prevalent in outbreaks in June. Mink astrovirus was detected in outbreaks of diarrhea in the growth period, though in a much lesser extent than in the pre-weaning period. The role of mink astrovirus in the diarrhea disease complex of mink remain to be investigated, and for that purpose this sensitive and robust RT-qPCR can be a valuable tool in the future.
|
|
| 18. |
- Båth, Magnus, 1974, et al.
(författare)
-
Investigation of image components affecting the detection of lung nodules in digital chest radiography
- 2005
-
Ingår i: Progress in Biomedical Optics and Imaging - Proceedings of SPIE. - : SPIE. - 1605-7422. ; 5749, s. 231-242
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this work was to investigate and quantify the effects of system noise, nodule location, anatomical noise and anatomical background on the detection of lung nodules in different regions of the chest x-ray. Simulated lung nodules of diameter 10 mm but with varying detail contrast were randomly positioned in four different kinds of images: 1) clinical images collected with a 200 speed CR system, 2) images containing only system noise (including quantum noise) at the same level as the clinical images, 3) clinical images with removed anatomical noise, 4) artificial images with similar power spectrum as the clinical images but random phase spectrum. An ROC study was conducted with 5 observers. The detail contrast needed to obtain an Az of 0.80, C0.8, was used as measure of detectability. Five different regions of the chest x-ray were investigated separately. The C0.8 of the system noise images ranged from only 2% (the hilar regions) to 20% (the lateral pulmonary regions) of those of the clinical images. Compared with the original clinical images, the C0.8 was 16% lower for the de-noised clinical images and 71% higher for the random phase images, respectively, averaged over all five regions. In conclusion, regarding the detection of lung nodules with a diameter of 10 mm, the system noise is of minor importance at clinically relevant dose levels. The removal of anatomical noise and other noise sources uncorrelated from image to image leads to somewhat better detection, but the major component disturbing the detection is the overlapping of recognizable structures, which are, however, the main aspect of an x-ray image.
|
|
| 19. |
- Chesnut, Randall, et al.
(författare)
-
A management algorithm for adult patients with both brain oxygen and intracranial pressure monitoring : the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC)
- 2020
-
Ingår i: Intensive Care Medicine. - : Springer. - 0342-4642 .- 1432-1238. ; 46:5, s. 919-929
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Current guidelines for the treatment of adult severe traumatic brain injury (sTBI) consist of high-quality evidence reports, but they are no longer accompanied by management protocols, as these require expert opinion to bridge the gap between published evidence and patient care. We aimed to establish a modern sTBI protocol for adult patients with both intracranial pressure (ICP) and brain oxygen monitors in place.Methods: Our consensus working group consisted of 42 experienced and actively practicing sTBI opinion leaders from six continents. Having previously established a protocol for the treatment of patients with ICP monitoring alone, we addressed patients who have a brain oxygen monitor in addition to an ICP monitor. The management protocols were developed through a Delphi-method-based consensus approach and were finalized at an in-person meeting.Results: We established three distinct treatment protocols, each with three tiers whereby higher tiers involve therapies with higher risk. One protocol addresses the management of ICP elevation when brain oxygenation is normal. A second addresses management of brain hypoxia with normal ICP. The third protocol addresses the situation when both intracranial hypertension and brain hypoxia are present. The panel considered issues pertaining to blood transfusion and ventilator management when designing the different algorithms.Conclusions: These protocols are intended to assist clinicians in the management of patients with both ICP and brain oxygen monitors but they do not reflect either a standard-of-care or a substitute for thoughtful individualized management. These protocols should be used in conjunction with recommendations for basic care, management of critical neuroworsening and weaning treatment recently published in conjunction with the Seattle International Brain Injury Consensus Conference.
|
|
| 20. |
- Chesnut, Randall M., et al.
(författare)
-
Perceived Utility of Intracranial Pressure Monitoring in Traumatic Brain Injury : A Seattle International Brain Injury Consensus Conference Consensus-Based Analysis and Recommendations
- 2023
-
Ingår i: Neurosurgery. - : Oxford University Press. - 0148-396X .- 1524-4040. ; 93:2, s. 399-408
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Intracranial pressure (ICP) monitoring is widely practiced, but the indications are incompletely developed, and guidelines are poorly followed. OBJECTIVE: To study the monitoring practices of an established expert panel (the clinical working group from the Seattle International Brain Injury Consensus Conference effort) to examine the match between monitoring guidelines and their clinical decision-making and offer guidance for clinicians considering monitor insertion.METHODS: We polled the 42 Seattle International Brain Injury Consensus Conference panel members' ICP monitoring decisions for virtual patients, using matrices of presenting signs (Glasgow Coma Scale [GCS] total or GCS motor, pupillary examination, and computed tomography diagnosis). Monitor insertion decisions were yes, no, or unsure (traffic light approach). We analyzed their responses for weighting of the presenting signs in decision-making using univariate regression.RESULTS: Heatmaps constructed from the choices of 41 panel members revealed wider ICP monitor use than predicted by guidelines. Clinical examination (GCS) was by far the most important characteristic and differed from guidelines in being nonlinear. The modified Marshall computed tomography classification was second and pupils third. We constructed a heatmap and listed the main clinical determinants representing 80% ICP monitor insertion consensus for our recommendations.CONCLUSION: Candidacy for ICP monitoring exceeds published indicators for monitor insertion, suggesting the clinical perception that the value of ICP data is greater than simply detecting and monitoring severe intracranial hypertension. Monitor insertion heatmaps are offered as potential guidance for ICP monitor insertion and to stimulate research into what actually drives monitor insertion in unconstrained, real-world conditions.
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
- Hawryluk, Gregory W. J., et al.
(författare)
-
A management algorithm for patients with intracranial pressure monitoring : the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC)
- 2019
-
Ingår i: Intensive Care Medicine. - : Springer. - 0342-4642 .- 1432-1238. ; 45:12, s. 1783-1794
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Management algorithms for adult severe traumatic brain injury (sTBI) were omitted in later editions of the Brain Trauma Foundation's sTBI Management Guidelines, as they were not evidence-based.Methods: We used a Delphi-method-based consensus approach to address management of sTBI patients undergoing intracranial pressure (ICP) monitoring. Forty-two experienced, clinically active sTBI specialists from six continents comprised the panel. Eight surveys iterated queries and comments. An in-person meeting included whole- and small-group discussions and blinded voting. Consensus required 80% agreement. We developed heatmaps based on a traffic-light model where panelists' decision tendencies were the focus of recommendations.Results: We provide comprehensive algorithms for ICP-monitor-based adult sTBI management. Consensus established 18 interventions as fundamental and ten treatments not to be used. We provide a three-tier algorithm for treating elevated ICP. Treatments within a tier are considered empirically equivalent. Higher tiers involve higher risk therapies. Tiers 1, 2, and 3 include 10, 4, and 3 interventions, respectively. We include inter-tier considerations, and recommendations for critical neuroworsening to assist the recognition and treatment of declining patients. Novel elements include guidance for autoregulation-based ICP treatment based on MAP Challenge results, and two heatmaps to guide (1) ICP-monitor removal and (2) consideration of sedation holidays for neurological examination.Conclusions: Our modern and comprehensive sTBI-management protocol is designed to assist clinicians managing sTBI patients monitored with ICP-monitors alone. Consensus-based (class III evidence), it provides management recommendations based on combined expert opinion. It reflects neither a standard-of-care nor a substitute for thoughtful individualized management.
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
- Juniper, E F, et al.
(författare)
-
Asthma quality of life during 1 year of treatment with budesonide with or without formoterol
- 1999
-
Ingår i: European Respiratory Journal. - 1399-3003. ; 14:5, s. 1038-1043
-
Tidskriftsartikel (refereegranskat)abstract
- The Formoterol and Corticosteroids Establishing Therapy (FACET) study has provided the first opportunity to examine the long-term effects of inhaled steroids and long-acting beta2-agonists on asthma-specific quality of life. The objectives of the present study were to: evaluate the effects of long-term (1 yr) formoterol and increasing doses of budesonide on asthma quality of life; 2) to determine whether initial improvements in quality of life are sustained when improvements in clinical indices persist; and 3) to evaluate the long-term relationship between changes in clinical indices and changes in quality of life. Of the 852 asthmatic adults enrolled, 470 from five countries participated in this quality of life evaluation. After a 4-week run-in on 1,600 microg budesonide, patients were randomized to either 200 microg (Bud200) or 800 microg budesonide (Bud800) in combination with either 24 microg formoterol (F) or placebo daily for 1 yr. The Asthma Quality of Life Questionnaire (AQLQ) was completed and conventional clinical indices measured at enrolment and randomization and on seven occasions during the following 12 months. During the run-in, there was an improvement in AQLQ score (changes (delta) in overall score approximately 0.50; p<0.0001). After randomization, there was a further improvement in the Bud800+F group (delta=0.21; p=0.028). One month post-randomization, improvements in all groups stabilized and were sustained throughout the 12 months in a pattern very similar to that observed for the conventional clinical indices. The correlation of individual patient changes in clinical indices and changes in AQLQ score during the 12-month randomized period were weak to moderate (maximum r=0.51). Improvements in quality of life, which were greatest in the 800 microg budesonide plus 24 microg formoterol group, were sustained throughout the 12 months in a similar manner to the clinical indices. Long-term changes in conventional clinical indices cannot be used to predict the effect of treatment on individual patient experience.
|
|
| 28. |
- Larsson, Veronica J., 1980-
(författare)
-
Characterization of the inner nuclear membrane protein Samp1, during interphase and mitosis
- 2018
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The nucleus, a hallmark in eukaryotic cells, contains the genome separating it from molecules in the cytoplasm. The nucleus is surrounded by a nuclear envelope consisting of two concentric membranes, the outer nuclear membrane and the inner nuclear membrane, the nuclear lamina and nuclear pore complexes. The cytoskeleton is physically connected with the nucleoskeleton by the LINC complexes, spanning the nuclear envelope. In this way, the cell surface is linked directly to chromatin. There are hundreds of unique inner nuclear membrane proteins, but today we only know the functions of a handful. The best characterized inner nuclear membrane proteins are involved in chromatin organization and gene regulation.This thesis focuses on Samp1, an integral membrane protein that localizes to the inner nuclear membrane during interphase. During mitosis, a fraction localizes to the mitotic spindle, which is responsible for accurate segregation of chromosomes.It is difficult to investigate inner nuclear membrane protein-protein interactions, because transmembrane proteins are often associated with the “hard-to-solubilize” nuclear lamina. MCLIP was developed as a method to detect interactions between proteins of the nuclear envelope in live cells. MCLIP has been valuable in identifying interaction partners of Samp1. In interphase, Samp1 distributes in distinct micro-domains of the inner nuclear membrane and interacts with the nuclear lamina, emerin and the LINC complex protein SUN1, suggesting that Samp1 might have a functional role associated with both the nucleoskeleton and cytoskeleton.In mitosis Samp1 distributes in filamentous membrane structures partially overlapping with kinetochore microtubules of the mitotic spindle. Samp1 binds directly to γ-tubulin and recruits γ-tubulin and Haus6 to the mitotic spindle and thus contributes to spindle assembly. Samp1 also interacts with Aurora B, a kinase important for k-fiber error correction at the kinetochores. Depletion of Samp1 caused an increased activation and distribution of Aurora B at the metaphase plate, decreased formation of stable k-fibers, metaphase prolongation and increased chromosome mis-segregation. Samp1 is the first transmembrane protein found to be involved in mitotic spindle assembly and stability, important for correct segregation of chromosomes.
|
|
| 29. |
- Lauten, Alexander, et al.
(författare)
-
Percutaneous Left-Ventricular Support With the Impella-2.5-Assist Device in Acute Cardiogenic Shock Results of the Impella-EUROSHOCK-Registry
- 2013
-
Ingår i: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 6:1, s. 23-30
-
Tidskriftsartikel (refereegranskat)abstract
- Background-Acute cardiogenic shock after myocardial infarction is associated with high in-hospital mortality attributable to persisting low-cardiac output. The Impella-EUROSHOCK-registry evaluates the safety and efficacy of the Impella-2.5-percutaneous left-ventricular assist device in patients with cardiogenic shock after acute myocardial infarction. Methods and Results-This multicenter registry retrospectively included 120 patients (63.6 +/- 12.2 years; 81.7% male) with cardiogenic shock from acute myocardial infarction receiving temporary circulatory support with the Impella-2.5-percutaneous left-ventricular assist device. The primary end point evaluated mortality at 30 days. The secondary end point analyzed the change of plasma lactate after the institution of hemodynamic support, and the rate of early major adverse cardiac and cerebrovascular events as well as long-term survival. Thirty-day mortality was 64.2% in the study population. After Impella-2.5-percutaneous left-ventricular assist device implantation, lactate levels decreased from 5.8 +/- 5.0 mmol/L to 4.7 +/- 5.4 mmol/L (P=0.28) and 2.5 +/- 2.6 mmol/L (P=0.023) at 24 and 48 hours, respectively. Early major adverse cardiac and cerebrovascular events were reported in 18 (15%) patients. Major bleeding at the vascular access site, hemolysis, and pericardial tamponade occurred in 34 (28.6%), 9 (7.5%), and 2 (1.7%) patients, respectively. The parameters of age >65 and lactate level >3.8 mmol/L at admission were identified as predictors of 30-day mortality. After 317 +/- 526 days of follow-up, survival was 28.3%. Conclusions-In patients with acute cardiogenic shock from acute myocardial infarction, Impella 2.5-treatment is feasible and results in a reduction of lactate levels, suggesting improved organ perfusion. However, 30-day mortality remains high in these patients. This likely reflects the last-resort character of Impella-2.5-application in selected patients with a poor hemodynamic profile and a greater imminent risk of death. Carefully conducted randomized controlled trials are necessary to evaluate the efficacy of Impella-2.5-support in this high-risk patient group.
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
- Pauwels, Romain A, et al.
(författare)
-
Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group
- 1997
-
Ingår i: New England Journal of Medicine. - 0028-4793. ; 337:20, s. 1405-1411
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The role of long-acting, inhaled beta2-agonists in treating asthma is uncertain. In a double-blind study, we evaluated the effects of adding inhaled formoterol to both lower and higher doses of the inhaled glucocorticoid budesonide. METHODS: After a four-week run-in period of treatment with budesonide (800 microg twice daily), 852 patients being treated with glucocorticoids were randomly assigned to one of four treatments given twice daily by means of a dry-powder inhaler (Turbuhaler): 100 microg of budesonide plus placebo, 100 microg of budesonide plus 12 microg of formoterol, 400 microg of budesonide plus placebo, or 400 microg of budesonide plus 12 microg of formoterol. Terbutaline was permitted as needed. Treatment continued for one year; we compared the frequency of exacerbations of asthma, symptoms, and lung function in the four groups. A severe exacerbation was defined by the need for oral glucocorticoids or a decrease in the peak flow to more than 30 percent below the base-line value on two consecutive days. RESULTS: The rates of severe and mild exacerbations were reduced by 26 percent and 40 percent, respectively, when formoterol was added to the lower dose of budesonide. The higher dose of budesonide alone reduced the rates of severe and mild exacerbations by 49 percent and 37 percent, respectively. Patients treated with formoterol and the higher dose of budesonide had the greatest reductions -- 63 percent and 62 percent, respectively. Symptoms of asthma and lung function improved with both formoterol and the higher dose of budesonide, but the improvements with formoterol were greater. CONCLUSIONS: In patients who have persistent symptoms of asthma despite treatment with inhaled glucocorticoids, the addition of formoterol to budesonide therapy or the use of a higher dose of budesonide may be beneficial. The addition of formoterol to budesonide therapy improves symptoms and lung function without lessening the control of asthma.
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
- Tattersfield, A E, et al.
(författare)
-
Exacerbations of asthma: a descriptive study of 425 severe exacerbations. The FACET International Study Group
- 1999
-
Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1535-4970. ; 160:2, s. 594-599
-
Tidskriftsartikel (refereegranskat)abstract
- The identification, prevention, and prompt treatment of exacerbations are major objectives of asthma management. We looked at change in PEF, symptoms, and use of rescue beta-agonists during the 425 severe exacerbations that occurred during a 12-mo parallel group study (FACET) in which low and high doses of budesonide with and without formoterol were compared in patients with asthma. Oral corticosteroids were prescribed for severe exacerbations, the main study end point, defined as the need for a course of oral corticosteroids (n = 311) or a reduction in morning PEF of > 30% on two consecutive days. PEF, symptoms, and bronchodilator use over the 14 d before and after the exacerbation were obtained from diary cards. Exacerbations were characterized by a gradual fall in PEF over several days, followed by more rapid changes over 2 to 3 d; an increase in symptoms and rescue beta-agonist use occurred in parallel, and both the severity and time course of the changes were similar in all treatment groups. Exacerbations identified by the need for oral corticosteroids were associated with more symptoms and smaller changes in PEF than those identified on the basis of PEF criteria. Female sex was the main patient characteristic associated with an increased risk of having a severe exacerbation. Exacerbations may be characterized predominantly by change in symptoms or change in PEF, but the pattern was not affected by the dose of inhaled corticosteroid or by whether the patient was taking formoterol.
|
|
| 36. |
|
|
| 37. |
- Ullman, Gustav, et al.
(författare)
-
On the extent of quantum noise limitation in digital chest radiography
- 2004
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The aim for this work was to study to what extent the detection of nodules is quantum noise limited, based on the combined results from a nodule-detection clinical trial and a Monte Carlo computational model of a digital chest imaging system. The Monte Carlo computer program computes measures of physical image quality such as image contrast, C and signalto-noise ratio, SNR for nodules of any size. A computed radiography (CR) imaging system used simulated. The patient anterior-posterior thickness was 25 cm and nodules with diameters between 1-40 mm were included. The image contrast and SNR was calculated for 1600 (40x40) positions in the chest image and averaged over five anatomical regions of interest (lateral pulmonary, retrocardial, hilar, lower- and upper mediastinal regions). Threshold contrasts for each region, Cth, corresponding to Az=0.80 for detecting a 10 mm nodule, were deduced from the clinical trial. A threshold is also used for the quantum noise signal-to-noise ratio, SNRth. The model computes the diameter of a disk-shaped object that is required to comply with the two criteria: SNR≥SNRth and C≥Cth. A system is said to be quantum noise limited when the nodule size required to fulfil both criteria is not limited by the contrast but by the SNR. The required nodule diameter is largest in the hilar region (25 mm) and smallest in the lateral pulmonary region (11 mm). When the threshold SNRth=25 is used, the lower mediastinal region is quantum noise limited already at low speed classes (S>100). The hilar region is never quantum noise limited at realistic speed classes (S<1000). The accuracy of this model will be tested in the future by more sophisticated modelling of anatomical background and noise in the SNR-expression.
|
|
| 38. |
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
|
|
