| 1. |
- Abdo, A. A., et al.
(författare)
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FERMI Large Area Telescope and multi-wavelength observations of the flaring activity of PKS 1510-089 between 2008 september and 2009 june
- 2010
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 721:2, s. 1425-1447
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Tidskriftsartikel (refereegranskat)abstract
- We report on the multi-wavelength observations of PKS 1510-089 (a flat spectrum radio quasar (FSRQ) at z = 0.361) during its high activity period between 2008 September and 2009 June. During this 11 month period, the source was characterized by a complex variability at optical, UV, and gamma-ray bands, on timescales down to 6-12 hr. The brightest gamma-ray isotropic luminosity, recorded on 2009 March 26, was similar or equal to 2 x 1048 erg s-1. The spectrum in the Fermi Large Area Telescope energy range shows a mild curvature described well by a log-parabolic law, and can be understood as due to the Klein-Nishina effect. The. -ray flux has a complex correlation with the other wavelengths. There is no correlation at all with the X-ray band, a weak correlation with the UV, and a significant correlation with the optical flux. The. -ray flux seems to lead the optical one by about 13 days. From the UV photometry, we estimated a black hole mass of similar or equal to 5.4 x 10(8)M(circle dot) and an accretion rate of similar or equal to 0.5M(circle dot) yr(-1). Although the power in the thermal and non-thermal outputs is smaller compared to the very luminous and distant FSRQs, PKS 1510-089 exhibits a quite large Compton dominance and a prominent big blue bump (BBB) as observed in the most powerful gamma-ray quasars. The BBB was still prominent during the historical maximum optical state in 2009 May, but the optical/ UV spectral index was softer than in the quiescent state. This seems to indicate that the BBB was not completely dominated by the synchrotron emission during the highest optical state. We model the broadband spectrum assuming a leptonic scenario in which the inverse Compton emission is dominated by the scattering of soft photons produced externally to the jet. The resulting model-dependent jet energetic content is compatible with a scenario in which the jet is powered by the accretion disk, with a total efficiency within the Kerr black hole limit.
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| 2. |
- Axelsson, P, et al.
(författare)
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Betamethasone does not prevent nausea and vomiting induced by ipecacuanha
- 2004
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 48:10, s. 1283-1286
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Tidskriftsartikel (refereegranskat)abstract
- Background: Corticosteroids reduce the incidence of PONV but the mode of action is not known. The purpose of this study was to evaluate if betamethasone has serotonin (5-HT) antagonistic effects. Ipecacuanha is known to release serotonin and therefore it was used to induce nausea and vomiting. The 5-HT3 antagonist ondansetron was used as a control substance. Methods: In a randomized, double-blind, cross-over, placebo-controlled study 10 healthy male and female volunteers (6 M/4F), mean age 19.5 (18-23) years, mean weight 69.7 (53-84) kg, were studied on three occasions separated by at least 1 week. They were randomly allocated to receive pretreatment with betamethasone 8 mg, ondansetron 8 mg, or normal saline 2 ml as placebo on each occasion, 15 min before oral ingestion of 30 ml of Ipecacuanha syrup. After ingestion of ipecacuanha, vomitings were recorded and the intensity of nausea was estimated with a visual analog scale during 2 h. Results: During the first 2 h after ingestion of ipecacuanha nine of the 10 volunteers vomited both after betamethasone and placebo. No volunteer vomited after ondansetron (P < 0.01 vs. betamethasone and placebo). The max VAS for nausea was significantly higher after betamethasone and placebo compared to ondansetron (P < 0.01). There were no statistically significant differences of the max VAS for nausea between betamethasone and placebo. Conclusion: This study in volunteers has shown that betamethasone does not prevent nausea and vomiting induced by oral intake of ipecacuanha syrup. As ipecacuanha releases 5-hydroxytryptamin, it can be concluded that betamethasone does not have 5-HT3 antagonistic effects.
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| 3. |
- Janson, Peter C. J., et al.
(författare)
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CpG methylation of the IFNG gene as a mechanism to induce immunosupression in tumor-infiltrating lymphocytes
- 2008
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Ingår i: Journal of Immunology. - 0022-1767 .- 1550-6606. ; 181:4, s. 2878-2886
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Tidskriftsartikel (refereegranskat)abstract
- The execution of appropriate gene expression patterns during immune responses is of eminent importance where CpG methylation has emerged as an essential mechanism for gene silencing. We have charted the methylation status of regulatory elements in the human IFNG gene encoding the signature cytokine of the Th1 response. Surprisingly, human naive CD4(+) T lymphocytes displayed hypermethylation at the IFNG promoter region, which is in sharp contrast to the completely demethylated status of this region in mice. Th1 differentiation induced demethylation of the IFNG promoter and the upstream conserved nucleotide sequence 1 enhancer region, whereas Th2-differentiated lymphocytes remained hypermethylated. Furthermore, CD19(+) B lymphocytes displayed hypomethylation at the IFNG promoter region with a similar pattern to Th1 effector cells. When investigating the methylation status among tumor-infiltrating CD4(+) T lymphocytes from patients with colon cancer, we found that tumor-infiltrating lymphocytes cells are inappropriately hypermethylated, and thus not confined to the Th1 lineage. In contrast, CD4(+) T cells from the tumor draining lymph node were significantly more demethylated than tumor-infiltrating lymphocytes. We conclude that there are obvious interspecies differences in the methylation status of the IFNG gene in naive CD4(+) T lymphocytes, where Th1 commitment in human lymphocytes involves demethylation before IFNG expression. Finally, investigations of tumor-infiltrating lymphocytes and CD4(+) cells from tumor draining lymph node demonstrate methylation of regulatory regions within key effector genes as an epigenetic mechanism of tumor-induced immunosupression.
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| 4. |
- Janson, Peter C. J., et al.
(författare)
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FOXP3 Promoter Demethylation Reveals the Committed Treg Population in Humans
- 2008
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 3:2, s. e1612-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Naturally occurring thymus derived regulatory T cells (Tregs) are central in the maintenance of self-tolerance. The transcription factor FOXP3 is crucial for the suppressive activity of Tregs and is considered the most specific marker for this population. However, human non regulatory T cells upregulate FOXP3 transiently upon activation which calls for other means to identify the Treg population. Since epigenetic mechanisms are involved in the establishment of stable gene expression patterns during cell differentiation, we hypothesized that the methylation profile of the FOXP3 promoter would allow the distinction of truly committed Tregs. Methodology/Principal Findings: Human CD4(+) CD25(hi) Tregs displayed a demethylated FOXP3 promoter (1.4%+/-0.95% SEM methylated) in contrast to CD4(+) CD25(lo) T cells which were partially methylated (27.9%+/-7.1%). Furthermore, stimulated CD4(+)CD25(lo) T cells transiently expressed FOXP3 but remained partially methylated, suggesting promoter methylation as a mechanism for regulation of stable FOXP3 expression and Treg commitment. In addition, transient FOXP3 expressing cells exhibited suppressive abilities that correlate to the methylation status of the FOXP3 promoter. As an alternative to bisulphite sequencing, we present a restriction enzyme based screening method for the identification of committed Tregs and apply this method to evaluate the effect of various culturing conditions. We show that a partial demethylation occurs in long-term cultures after activation, whereas the addition of TGF-beta and/or IL-10 does not induce any additional change in methylation level. Conclusions/Significance: The unique FOXP3 promoter methylation profile in Tregs suggests that a demethylated pattern is a prerequisite for stable FOXP3 expression and suppressive phenotype. Presently, FOXP3 is used to identify Tregs in several human diseases and there are future implications for adoptive Treg transfer in immunotherapy. In these settings there is a need to distinguish true Tregs from transiently FOXP3(+) activated T cells. The screening method we present allows this distinction and enables the identification of cells suitable for in vitro expansions and clinical use.
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| 5. |
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| 6. |
- Walldén, Jakob, et al.
(författare)
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The delay of gastric emptying induced by remifentanil is not influenced by posture
- 2004
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Ingår i: Anesthesia and Analgesia. - 0003-2999 .- 1526-7598. ; 99:2, s. 429-434
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Tidskriftsartikel (refereegranskat)abstract
- Posture has an effect on gastric emptying. In this study, we investigated whether posture influences the delay in gastric emptying induced by opioid analgesics. Ten healthy male subjects underwent 4 gastric emptying studies with the acetaminophen method. On two occasions the subjects were given a continuous infusion of remifentanil (0.2 mug . kg(-1) . min(-1)) while lying either on the right lateral side in a 20degrees head-up position or on the left lateral side in a 20degrees head-down position. On two other occasions no infusion was given, and the subjects were studied lying in the two positions. When remifentanil was given, there were no significant differences between the two postures in maximal acetaminophen concentration (right side, 34 mumol . L-1, versus left side, 16 mumol . L-1), time taken to reach the maximal concentration (94 versus 109 min), or area under the serum acetaminophen concentration time curve from 0 to 60 min (962 versus 197 min . mumol - L-1). In the control situation, there were differences between the postures in maximal acetaminophen concentration (138 versus 94 mumol . L-1, P < 0.0001) and area under the serum acetaminophen concentration time curves from 0 to 60 min (5092 versus 3793 min . mumol . L-1, P < 0.0001), but there was no significant difference in time taken to reach the maximal concentration (25 versus 47 min). Compared with the control situation, remifentanil delayed gastric emptying in both postures. We conclude that remifentanil delays gastric emptying and that this delay is not influenced by posture.
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| 7. |
- Wattwil, Magnus, et al.
(författare)
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Dexamethasone is as effective as ondansetron for the prevention of postoperative nausea and vomiting following breast surgery
- 2003
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 47:7, s. 823-827
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Postoperative nausea and vomiting remain a common problem following breast surgery. This study assesses whether dexamethasone is as effective as ondansetron in the control of postoperative nausea and vomiting (PONV). Methods: Eighty ASA I-III patients undergoing breast surgery for carcinoma of the breast were included in the study. Following premedication with diazepam 5-10 mg, patients were induced with fentanyl 50 µg and propofol 2-2.5 mg kg-1. A larynx mask was inserted and anesthesia maintained with sevoflurane in oxygen and nitrous oxide. Patients were then randomly divided into two groups: Group D (dexamethasone) was given 4 mg dexamethasone i.v. after induction and Group O (ondansetron) was given 4 mg ondansetron at the same time point. Postoperatively, nausea, vomiting and pain were recorded at 1-h intervals during 4 h, and thereafter every 4h during 24 h. Results: The incidence of PONV during 24h was 37% and 33% in Group D and Group O, respectively (NS). No differences were found between the groups in the incidence of post-operative nausea, vomiting or pain at the different time intervals. No differences were found in the incidence of PONV in smokers vs. non-smokers. No side-effects of these drugs were observed. Conclusions: Ondansetron 4 mg or dexamethasone 4 mg are equally effective in the prevention of postoperative nausea and vomiting following breast surgery. Other factors being similar, the difference in cost between these drugs would favor the use of dexamethasone instead of ondansetron when monotherapy against PONV is used. © Acta Anaesthesiologica Scandinavica.
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| 8. |
- Wattwil, Magnus, et al.
(författare)
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Perioperative gastric emptying is not a predictor of early postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy
- 2002
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Ingår i: Anesthesia and Analgesia. - : Ovid Technologies (Wolters Kluwer Health). - 0003-2999 .- 1526-7598. ; 95:2, s. 476-479
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Tidskriftsartikel (refereegranskat)abstract
- It is not known whether patients with postoperative nausea and vomiting (PONV) have delayed gastric emptying compared with patients without PONV. We compared the perioperative rate of gastric emptying in patients experiencing PONV with the rate in those without PONV immediately after laparoscopic cholecystectomy. Gastric emptying was studied by the acetaminophen method. Acetaminophen is not absorbed from the stomach but is rapidly absorbed from the small intestine, and the rate of gastric emptying therefore determines the rate of absorption of acetaminophen administered into the stomach. Forty patients (ASA physical status I and II) were included in the study. After the induction of anesthesia, a gastric tube was positioned in the stomach and 1.5 g of acetaminophen dissolved in 200 mL of water was administered. Venous blood samples for the determination of serum acetaminophen concentrations were taken before and at 15-min intervals during a period of 180 min after the administration of acetaminophen. Twenty-six patients experienced nausea during the first 4 h postoperatively. The other 14 patients had no nausea. There were no statistically significant differences in the maximal acetaminophen concentration, the time taken to reach the maximal concentration, or the area under the serum acetaminophen concentration time curves from 0 to 60, 0-120, and 0-180 min between the groups of patients with or without PONV. We did not find any relationship between postoperative gastric emptying and PONV, and therefore gastric emptying is not a predictor of PONV.
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