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1.
  • Albrecht, Daniel S., et al. (författare)
  • Brain glial activation in fibromyalgia - A multi-site positron emission tomography investigation
  • 2019
  • Ingår i: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 75, s. 72-83
  • Tidskriftsartikel (refereegranskat)abstract
    • Fibromyalgia (FM) is a poorly understood chronic condition characterized by widespread musculoskeletal pain, fatigue, and cognitive difficulties. While mounting evidence suggests a role for neuroinflammation, no study has directly provided evidence of brain glial activation in FM. In this study, we conducted a Positron Emission Tomography (PET) study using [C-11]PBR28, which binds to the translocator protein (TSPO), a protein upregulated in activated microglia and astrocytes. To enhance statistical power and generalizability, we combined datasets collected independently at two separate institutions (Massachusetts General Hospital [MGH] and Karolinska Institutet [KI]). In an attempt to disentangle the contributions of different glial cell types to FM, a smaller sample was scanned at KI with [C-11]-L-deprenyl-D2 PET, thought to primarily reflect astrocytic (but not microglial) signal. Thirty-one FM patients and 27 healthy controls (HC) were examined using [C-11]PBR28 PET. 11 FM patients and 11 HC were scanned using [C-11]-L-deprenyl-D2 PET. Standardized uptake values normalized by occipital cortex signal (SUVR) and distribution volume (V-T) were computed from the [C-11]PBR28 data. [C-11]-L-deprenyl-D2 was quantified using lambda k(3). PET imaging metrics were compared across groups, and when differing across groups, against clinical variables. Compared to HC, FM patients demonstrated widespread cortical elevations, and no decreases, in [C-11]PBR28 ITT and SUVR, most pronounced in the medial and lateral walls of the frontal and parietal lobes. No regions showed significant group differences in [C-11]-L-deprenyl-Ds signal, including those demonstrating elevated [C-11] PBR28 signal in patients (p's >= 0.53, uncorrected). The elevations in [C-11]PBR28 V-T and SUVR were correlated both spatially (i.e., were observed in overlapping regions) and, in several areas, also in terms of magnitude. In exploratory, uncorrected analyses, higher subjective ratings of fatigue in FM patients were associated with higher [C-11] PBR28 SUVR in the anterior and posterior middle cingulate cortices (p's < 0.03). SUVR was not significantly associated with any other clinical variable. Our work provides the first in vivo evidence supporting a role for glial activation in FM pathophysiology. Given that the elevations in [C-11]PBR28 signal were not also accompanied by increased [C-11]-deprenyl-D2 signal, our data suggests that microglia, but not astrocytes, may be driving the TSPO elevation in these regions. Although [C-11]-L-deprenyl-D2 signal was not found to be increased in FM patients, larger studies are needed to further assess the role of possible astrocytic contributions in FM. Overall, our data support glial modulation as a potential therapeutic strategy for FM.
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2.
  • Dellgren, Linus, et al. (författare)
  • Phenotypic screening for quinolone resistance in Escherichia coli
  • 2019
  • Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : SPRINGER. - 0934-9723 .- 1435-4373. ; 38:9, s. 1765-1771
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent studies show that rectal colonization with low-level ciprofloxacin-resistant Escherichia coli (ciprofloxacin minimal inhibitory concentration (MIC) above the epidemiological cutoff point, but below the clinical breakpoint for resistance), i.e., in the range amp;gt; 0.06-0.5 mg/L is an independent risk factor for febrile urinary tract infection after transrectal ultrasound-guided biopsy (TRUS-B) of the prostate, adding to the other risk posed by established ciprofloxacin resistance in E. coli (MIC amp;gt; 0.5 mg/L) as currently defined. We aimed to identify the quinolone that by disk diffusion best discriminates phenotypic wild-type isolates (ciprofloxacin MIC amp;lt;= 0.06 mg/L) of E. coli from isolates with acquired resistance, and to determine the resistance genotype of each isolate. The susceptibility of 108 E. coli isolates was evaluated by ciprofloxacin, levofloxacin, moxifloxacin, nalidixic acid, and pefloxacin disk diffusion and correlated to ciprofloxacin MIC (broth microdilution) using EUCAST methodology. Genotypic resistance was identified by PCR and DNA sequencing. The specificity was 100% for all quinolone disks. Sensitivity varied substantially, as follows: ciprofloxacin 59%, levofloxacin 46%, moxifloxacin 59%, nalidixic acid 97%, and pefloxacin 97%. We suggest that in situations where low-level quinolone resistance might be of importance, such as when screening for quinolone resistance in fecal samples pre-TRUS-B, a pefloxacin (S amp;gt;= 24 mm) or nalidixic acid (S amp;gt;= 19 mm) disk, or a combination of the two, should be used. In a setting where plasmid-mediated resistance is prevalent, pefloxacin might perform better than nalidixic acid.
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3.
  • Frank, Jon, 1981- (författare)
  • Essays on Corporate Finance and Asset Pricing
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Essay 1 (with Mattias Hamberg): We study the performance of family firms with large controlling owners using unique hand-collected Swedish data; and consistent with previous studies, we find that founding family firms perform significantly better than other firms. The data allows us to also identify firms with long term non-founding owners (LTNFOs). Because of their long term involvement these owners have similar monitoring abilities. We also find that they use control enhancing mechanisms to a similar extent. However, firms dominated by LTNFOs perform considerably worse. Founders are somewhat more involved in operations and the involvement has a positive association with operating performance. For firms with LTNFOs, the involvement effect is none or negative. The analysis shows that ownership is more important than involvement: The effect is positive for founding family firms, and negative for firms with LTNFOs. In sum, the results challenge the claim that information-advantages and superior monitoring abilities lead to the excess performance of founding family firms.
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  • Holmbom, Martin, 1984-, et al. (författare)
  • Fluoroquinolone-resistant Escherichia coli among the rectal flora is the predominant risk factor for severe infection after transrectal ultrasound-guided prostate biopsy : a prospective observational study
  • 2023
  • Ingår i: Scandinavian journal of urology. - : Medical Journals Sweden. - 2168-1805 .- 2168-1813. ; 58, s. 32-37
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Infection of the prostate gland following biopsy, usually with Escherichia coli, is a common complication, despite the use of antimicrobial prophylaxis. A fluoroquinolone (FQ) is commonly prescribed as prophylaxis. Worryingly, the rate of fluoroquinolone-resistant (FQ-R) E. coli species has been shown to be increasing. OBJECTIVE: This study aimed to identify risk factors associated with infection after transrectal ultrasound-guided prostate biopsy (TRUS-Bx). METHODS: This was a prospective study on patients undergoing TRUS-Bx in southeast Sweden. Prebiopsy rectal and urine cultures were obtained, and antimicrobial susceptibility and risk-group stratification were determined. Multivariate analyses were performed to identify independent risk factors for post-biopsy urinary tract infection (UTI) and FQ-R E. coli in the rectal flora. RESULTS: In all, 283 patients were included, of whom 18 (6.4%) developed post-TRUS-Bx UTIs. Of these, 10 (3.5%) had an UTI without systemic inflammatory response syndrome (SIRS) and 8 (2.8%) had a UTI with SIRS. Being in the medium- or high-risk groups of infectious complications was not an independent risk factor for UTI with SIRS after TRUS-Bx, but low-level FQ-resistance (minimum inhibitory concentration (MIC): 0.125-0.25 mg/L) or FQ-resistance (MIC > 0.5 mg/L) among E. coli in the faecal flora was. Risk for SIRS increased in parallel with increasing degrees of FQ-resistance. Significant risk factor for harbouring FQ-R E.coli was travelling outside Europe within the previous 12 months. CONCLUSION: The predominant risk factor for UTI with SIRS after TRUS-Bx was FQ-R E. coli among the faecal flora. The difficulty in identifying this type of risk factor demonstrates a need for studies on the development of a general approach either with rectal swab culture for targeted prophylaxis, or prior rectal preparation with a bactericidal agent such as povidone-iodine before TRUS-Bx to reduce the risk of FQ-R E. coli-related infection.
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6.
  • Kanegawa, Naoki, et al. (författare)
  • In vivo evidence of a functional association between immune cells in blood and brain in healthy human subjects
  • 2016
  • Ingår i: Brain, behavior, and immunity. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0889-1591 .- 1090-2139. ; 54, s. 149-157
  • Tidskriftsartikel (refereegranskat)abstract
    • Microglia, the resident macrophages in the central nervous system, are thought to be maintained by a local self-renewal mechanism. Although preclinical and in vitro studies have suggested that the brain may contain immune cells also from peripheral origin, the functional association between immune cells in the periphery and brain at physiological conditions is poorly understood. We examined 32 healthy individuals using positron emission tomography (PET) and [C-11]PBR28, a radioligand for the 18-kDa translocator protein (TSPO) which is expressed both in brain microglia and blood immune cells. In 26 individuals, two measurements were performed with varying time intervals. In a subgroup of 19 individuals, of which 12 had repeat examinations, leukocyte numbers in blood was measured on each day of PET measurements. All individuals were genotyped for TSPO polymorphism and categorized as high, mixed, and low affinity binders. We assessed TSPO binding expressed as total distribution volume of [C-11]PBR28 in brain and in blood cells. TSPO binding in brain was strongly and positively correlated to binding in blood cells both at baseline and when analyzing change between two PET examinations. Furthermore, there was a significant correlation between change of leukocyte numbers and change in TSPO binding in brain, and a trend level correlation to change in TSPO binding in blood cells. These in vivo findings indicate an association between immunological cells in blood and brain via intact BBB, suggesting a functional interaction between these two compartments, such as interchange of peripherally derived cells or a common regulatory mechanism. Measurement of radioligand binding in blood cells may be a way to control for peripheral immune function in PET studies using TSPO as a marker of brain immune activation. (C) 2016 Elsevier Inc. All rights reserved.
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7.
  • Liwing, Johan, et al. (författare)
  • Improved survival in myeloma patients : starting to close in on the gap between elderly patients and a matched normal population
  • 2014
  • Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 164:5, s. 684-693
  • Tidskriftsartikel (refereegranskat)abstract
    • The outcome for multiple myeloma patients has improved since the introduction of bortezomib, thalidomide and lenalidomide. However, studies comparing new and conventional treatment include selected patient groups. We investigated consecutive patients (n = 1638) diagnosed in a defined period and compared survival with a gender- and age-matched cohort Swedish population (n = 9 340 682). Median overall survival for non-high-dose treated patients was 2.8 years. The use of bortezomib, thalidomide or lenalidomide in first line therapy predicted a significantly longer overall survival (median 4.9 years) compared to conventional treatment (2.3 years). Among non-high-dose treated patients receiving at least 2 lines with bortezomib, thalidomide or lenalidomide, 69% and 63% have survived at 3 and 5 years as compared to 48% and 22% with conventional drugs and 88% and 79% in the matched cohort populations, respectively. The median overall survival in high-dose treated patients was 6.9 years. Of these patients, 84% survived at 3 years and 70% at 5 years as compared to 98% and 95% in the matched cohort population. Overall survival in the best non-high-dose treated outcome group is closing the gap with the matched cohort. Upfront use of new drugs is clearly better than waiting until later lines of treatment.
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9.
  • Oxenswärdh, Anette, 1956- (författare)
  • Ansvarsförhållanden vid skolutveckling
  • 2011
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Relations of Responsibility in School DevelopmentABSTRACTThe starting point of this study is the changed governance of schools in Swe- den. Decentralization has not only increased the freedom of schools but also responsibility at the different levels of the school system. This in turn has given greater scope for interpreting the assignment. In recent years, however, a cer- tain return to regulation has been evident. Theoretically the concept of respon- sibility is elucidated as a term in philosophy, organisation theory, and psychology-education. Responsibility in school can be described as a relation- ship between the commissioner’s exaction of responsibility and the contrac- tor’s assumption of responsibility. This can cause uncertainty in matters of responsibility. Active school measures may be viewed as a way to clarify re- sponsibility issues. For this study, two models of school development have been selected in order to study how they affect the school actors’ understan- ding of assignment and responsibility. Two case studies examine a number of conceptual dimensions that illustrate different aspects of the assumption of re- sponsibility.The results show that these two development models and the active measures to which they give rise shape in various ways the actors’ under- standing of assignment and responsibility. These can be considered to place the emphasis on different parts of the control system. The Scope for Action Model emphasizes the role of the local school with the aid of a bottom-up strategy as regards the school’s assumption of responsibility. The Effective Schools Model emphasizes the political level in a more top-down strategy. This means, in practice, that the Scope for Action Model for school devel- opment tries with the aid of culture analysis to clarify responsibility relations by making the actors in the organization aware of their accountability and the potential involved in their assignment. The Effective Schools Model, in contrast, clarifies relations of responsibility by pointing out deficiencies in the school organization in relation to the assignment and the responsibility it entails. The main results show that the school development models contrib- uted to increased cooperation between professionals, partly by exposing the organization and its boundaries, management, and different occupational roles. The cooperation exposes the obstacles but also the opportunities for change and development in the school’s own organization.Another important finding is that, in the work of school development, there was heavy focus on making activities more pupil-oriented by highlighting the task of both upbringing and teaching among all staff. Shortage of time, deficient organizational structures, and increased administration were per- ceived as obstructing the fulfilment of the assignment.A further finding is that the school development models led to the exposure and creation of responsibility structures in the schools. Structures revealed inc- luded the organizational structure, management structures, communication and cooperation structures such as the teacher team and different kinds of deve- lopment groups. Responsibility structures were created through firmer structu- ring of cooperation between teachers and parents and through the formation of groups for cooperation and development.All these active measures furthered the individual and collective learning processes through which the professionals’ understanding of assignment and responsibility is (re)shaped. This understanding in turn constitutes an essential part of the professionals’ competence development and professional develop- ment. Some conclusions that can be drawn from the study are that knowledge of the school’s responsibility reduces the discrepancy and helps professionals to improve their competence and develop the school. The professionals’ auto- nomy is essential for increased commitment, motivation, and understanding.Proceeding from the professionals’ own needs when implementing de- velopment measures further increases their motivation and serves as a motor driving the work of development.The learning process should be staged and designed as different arenas for more effectively satisfying the different needs of competence in the pro- fessionals. School development as learning should be continuous, with the aid of organization, support, leadership, and encouragement. School devel- opment should be the responsibility of all levels. 
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10.
  • Plaven-Sigray, Pontus, et al. (författare)
  • Accuracy and reliability of [C-11]PBR28 specific binding estimated without the use of a reference region
  • 2019
  • Ingår i: NeuroImage. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1053-8119 .- 1095-9572. ; 188, s. 102-110
  • Tidskriftsartikel (refereegranskat)abstract
    • [C-11]PBR28 is a positron emission tomography radioligand used to examine the expression of the 18 kDa translocator protein (TSPO). TSPO is located in glial cells and can function as a marker for immune activation. Since TSPO is expressed throughout the brain, no true reference region exists. For this reason, an arterial input function is required for accurate quantification of [C-11]PBR28 binding and the most common outcome measure is the total distribution volume (V-T). Notably, V-T reflects both specific binding and non-displaceable binding. Therefore, estimates of specific binding, such as binding potential (e.g. BPND) and specific distribution volume (V-S) should theoretically be more sensitive to underlying differences in TSPO expression. It is unknown, however, if unbiased and accurate estimates of these outcome measures are obtainable for [C-11]PBR28. The Simultaneous Estimation (SIME) method uses time-activity-curves from multiple brain regions with the aim to obtain a brain-wide estimate of the non-displaceable distribution volume (V-ND), which can subsequently be used to improve the estimation of BPND and V-S. In this study we evaluated the accuracy of SIME-derived V-ND, and the reliability of resulting estimates of specific binding for [C-11]PBR28, using a combination of simulation experiments and in vivo studies in healthy humans. The simulation experiments, based on data from 54 unique [C-11]PBR28 examinations, showed that V-ND values estimated using SIME were both precise and accurate. Data from a pharmacological competition challenge (n = 5) showed that SIME provided V-ND values that were on average 19% lower than those obtained using the Lassen plot, but similar to values obtained using the Likelihood-Estimation of Occupancy technique. Test-retest data (n = 11) showed that SIME-derived V-S values exhibited good reliability and precision, while larger variability was observed in SIME-derived BPND values. The results support the use of SIME for quantifying specific binding of [C-11]PBR28, and suggest that V-S can be used in complement to the conventional outcome measure V-T. Additional studies in patient cohorts are warranted.
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12.
  • Saudi, Aws, et al. (författare)
  • Immune-activated B cells are dominant in prostate cancer
  • 2023
  • Ingår i: Cancers. - : MDPI. - 2072-6694. ; 15:3
  • Tidskriftsartikel (refereegranskat)abstract
    • B cells are multifaceted immune cells responding robustly during immune surveillance against tumor antigens by presentation to T cells and switched immunoglobulin production. However, B cells are unstudied in prostate cancer (PCa). We used flow cytometry to analyze B-cell subpopulations in peripheral blood and lymph nodes from intermediate-high risk PCa patients. B-cell subpopulations were related to clinicopathological factors. B-cell-receptor single-cell sequencing and VDJ analysis identified clonal B-cell expansion in blood and lymph nodes. Pathological staging was pT2 in 16%, pT3a in 48%, and pT3b in 36%. Lymph node metastases occurred in 5/25 patients (20%). Compared to healthy donors, the peripheral blood CD19+ B-cell compartment was significantly decreased in PCa patients and dominated by naïve B cells. The nodal B-cell compartment had significantly increased fractions of CD19+ B cells and switched memory B cells. Plasmablasts were observed in tumor-draining sentinel lymph nodes (SNs). VDJ analysis revealed clonal expansion in lymph nodes. Thus, activated B cells are increased in SNs from PCa patients. The increased fraction of switched memory cells and plasmablasts together with the presence of clonally expanded B cells indicate tumor-specific T-cell-dependent responses from B cells, supporting an important role for B cells in the protection against tumors.
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13.
  • Sjöquist, Emma S., et al. (författare)
  • Physical Activity Coaching of Patients with Rheumatoid Arthritis in Everyday Practice : A Long-term Follow-up
  • 2011
  • Ingår i: Musculoskeletal Care. - Chichester : John Wiley & Sons. - 1478-2189 .- 1557-0681. ; 9:2, s. 75-85
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To investigate the long-term effects on perceived general health, disease activity, pain, activity limitation and cognitive behavioural factors of a one-year coaching programme performed in ordinary physical therapy practice to promote the adoption of health-enhancing physical activity in patients with early rheumatoid arthritis (RA).METHODS: A total of 228 patients with early RA, from 10 rheumatology clinics in Sweden, were randomly assigned to an intervention group (IG; n = 94) or a control group (CG; n = 134). The IG was coached by physical therapists during the first year to adopt health-enhancing levels of physical activity (30 minutes/day, moderately intensive, ≥ 4 days/week). No coaching was given during the subsequent year between post-intervention and follow-up. Follow-up assessment consisted of a postal questionnaire on physical activity and of visual analogue scales for ratings of general health perception and pain. The Health Assessment Questionnaire Disability Index (HAQ) and the Disease Activity Score in 28 joints (DAS 28) were collected at regular medical check-ups.RESULTS: Sixty-five (69%) participants in the IG and 92 (69%) in the CG completed the entire study period by filling in the follow-up questionnaire on physical activity two years after baseline. The intervention seemed to lack any significant influence on long-term outcome. However, different patterns of change in physical activity behaviour were observed in the two groups.CONCLUSIONS: No long-term improvement in perceived general health or other outcomes were found in the follow-up. This may partly be because the intervention lacked several important behavioural elements for physical activity maintenance. Copyright © 2011 John Wiley & Sons, Ltd.
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14.
  • Stjernman Forsberg, Lovisa, et al. (författare)
  • Leaching of metals from oxidising sulphide mine tailings with and without sewage sludge application
  • 2008
  • Ingår i: Water, Air and Soil Pollution. - : Springer Science and Business Media LLC. - 0049-6979 .- 1573-2932. ; 194:1-4, s. 331-341
  • Tidskriftsartikel (refereegranskat)abstract
    • A 20-month column experiment investigated leaching of Al, Cu, Mn, Ni, Zn, Cd and Pb during sulphide oxidation in mine tailings with and without sewage sludge (SS) amendment. Leachate pH decreased gradually in all columns during the experiment, irrespective of treatment, due to sulphide oxidation. As the degree of sulphide oxidation, and thus the pH trajectory, differed between replicates (n=3), running data for each column used are reported separately and the relationships between sulphide oxidation, metal leaching and treatment in each column compared. Mean pH in the columns correlated negatively with total amounts of leached SO4 (2-). In the beginning of the experiment the leachate concentrations of Al, Cu, Zn, Ni and Pb were higher in SS-treated columns due to high initial concentrations of dissolved organic carbon. As leaching proceeded, however, the amounts of Al, Cu, Mn and Ni leached from the columns were closely related to the degree of sulphide oxidation in each column, i.e. to its mean pH. There were no statistically significant differences between treatments regarding the total amounts of metals leached and thus addition of sewage sludge to the tailings appeared to play a minor role for metal leaching patterns. Peak concentrations of Al and Cu in the leachate from untreated tailings and of Zn in the leachate from both untreated and SS-treated tailings at pH 4 exceeded national background values for groundwater.
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15.
  • Tamm, Sandra, et al. (författare)
  • Evidence of fatigue, disordered sleep and peripheral inflammation, but not increased brain TSPO expression, in seasonal allergy : A [11C]PBR28 PET study
  • 2018
  • Ingår i: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 68, s. 146-157
  • Tidskriftsartikel (refereegranskat)abstract
    • Allergy is associated with non-specific symptoms such as fatigue, sleep problems and impaired cognition. One explanation could be that the allergic inflammatory state includes activation of immune cells in the brain, but this hypothesis has not been tested in humans. The aim of the present study was therefore to investigate seasonal changes in the glial cell marker translocator protein (TSPO), and to relate this to peripheral inflammation, fatigue and sleep, in allergy. We examined 18 patients with severe seasonal allergy, and 13 healthy subjects in and out-of pollen season using positron emission tomography (n = 15/13) and the TSPO radioligand [11C]PBR28. In addition, TNF-α, IL-5, IL-6, IL-8 and IFN-γ were measured in peripheral blood, and subjective ratings of fatigue and sleepiness as well as objective and subjective sleep were investigated. No difference in levels of TSPO was seen between patients and healthy subjects, nor in relation to pollen season. However, allergic subjects displayed both increased fatigue, sleepiness and increased percentage of deep sleep, as well as increased levels of IL-5 and TNF-α during pollen season, compared to healthy subjects. Allergic subjects also had shorter total sleep time, regardless of season. In conclusion, allergic subjects are indicated to respond to allergen exposure during pollen season with a clear pattern of behavioral disruption and peripheral inflammatory activation, but not with changes in brain TSPO levels. This underscores a need for development and use of more specific markers to understand brain consequences of peripheral inflammation that will be applicable in human subjects.
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16.
  • Tamm, Sandra, et al. (författare)
  • Objective and Subjective Sleep in Rheumatoid Arthritis and Severe Seasonal Allergy : Preliminary Assessments of the Role of Sickness, Central and Peripheral Inflammation
  • 2021
  • Ingår i: Nature and Science of Sleep. - : Dove Medical Press. - 1179-1608. ; 13, s. 775-789
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Disturbed sleep in inflammatory disorders such as allergy and rheumatoid arthritis (RA) is common and may be directly or indirectly related to disease processes, but has not been well characterized in these patient groups, especially not with objective methods.Aim: The present study aimed to characterize objective and subjective sleep in patients with allergy or RA using sleep diaries, one-channel EEG and actigraphy. It also aimed to investigate if sleep measures were associated with central immune activation, assessed using translocator protein (TSPO) positron emission tomography, as well as cytokine markers of peripheral inflammation and disease-specific symptoms or general symptoms of sickness.Methods: In total, 18 patients with seasonal pollen allergy, 18 patients with RA and 26 healthy controls were included in the study. Allergy patients and matched controls were assessed twice, in and out of pollen season, and RA patients and controls were assessed once. Sleep was recorded for approximately 1 week at each occasion.Results: Patients with allergy had increased levels of slow-wave sleep during pollen season. In contrast, patients with RA had less SWS compared to healthy controls, while no differences were observed in sleep duration or subjective sleep quality. Across groups, neither proinflammatory cytokines, grey matter TSPO levels nor general sickness symptoms were associated with objective or subjective measures of sleep. Rhinitis, but not conjunctivitis, was correlated to worse subjective sleep and more slow wave sleep in allergy. Functional status, but not disease activity, predicted lower subjective sleep in RA.Conclusion: This study tentatively indicates that both patients with allergy and RA display sleep alterations but does not support inflammation as an independent predictor of the sleep disturbance across these patient groups.
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17.
  • Tuisku, Jouni, et al. (författare)
  • Effects of age, BMI and sex on the glial cell marker TSPO : a multicentre [11C]PBR28 HRRT PET study
  • 2019
  • Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer. - 1619-7070 .- 1619-7089. ; 46:11, s. 2329-2338
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose The purpose of this study was to investigate the effects of ageing, sex and body mass index (BMI) on translocator protein (TSPO) availability in healthy subjects using positron emission tomography (PET) and the radioligand [C-11]PBR28. Methods [C-11]PBR28 data from 140 healthy volunteers (72 males and 68 females; N = 78 with HAB and N = 62 MAB genotype; age range 19-80 years; BMI range 17.6-36.9) were acquired with High Resolution Research Tomograph at three centres: Karolinska Institutet (N = 53), Turku PET centre (N = 62) and Yale University PET Center (N = 25). The total volume of distribution (V-T) was estimated in global grey matter, frontal, temporal, occipital and parietal cortices, hippocampus and thalamus using multilinear analysis 1. The effects of age, BMI and sex on TSPO availability were investigated using linear mixed effects model, with TSPO genotype and PET centre specified as random intercepts. Results There were significant positive correlations between age and V-T in the frontal and temporal cortex. BMI showed a significant negative correlation with V-T in all regions. Additionally, significant differences between males and females were observed in all regions, with females showing higher V-T. A subgroup analysis revealed a positive correlation between V-T and age in all regions in male subjects, whereas age showed no effect on TSPO levels in female subjects. Conclusion These findings provide evidence that individual biological properties may contribute significantly to the high variation shown in TSPO binding estimates, and suggest that age, BMI and sex can be confounding factors in clinical studies.
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18.
  • Waage, Anders, et al. (författare)
  • Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma
  • 2010
  • Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 116:9, s. 1405-1412
  • Tidskriftsartikel (refereegranskat)abstract
    • In this double-blind, placebo-controlled study, 363 patients with untreated multiple myeloma were randomized to receive either melphalan-prednisone and thalidomide (MPT) or melphalan-prednisone and placebo (MP). The dose of melphalan was 0.25 mg/kg and prednisone was 100 mg given daily for 4 days every 6 weeks until plateau phase. The dose of thalidomide/placebo was escalated to 400 mg daily until plateau phase and thereafter reduced to 200 mg daily until progression. A total of 357 patients were analyzed. Partial response was 34% and 33%, and very good partial response or better was 23% and 7% in the MPT and MP arms, respectively (P < .001). There was no significant difference in progression-free or overall survival, with median survival being 29 months in the MPT arm and 32 months in the MP arm. Most quality of life outcomes improved equally in both arms, apart from constipation, which was markedly increased in the MPT arm. Constipation, neuropathy, non-neuropathy neurologic toxicity, and skin reactions were significantly more frequent in the MPT arm. The number of thromboembolic events was equal in the 2 treatment arms. In conclusion, MPT had a significant antimyeloma effect, but this did not translate into improved survival. This trial was registered at www.clinicaltrials.
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