| 1. |
- Berg, Thomas, 1975-
(författare)
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Medical Treatment and Grading of Bell's Palsy
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The main aim of this thesis was to evaluate the effect of prednisolone and valaciclovir in a large number of Bell's palsy patients. The incidence and intensity of pain around the ear, in the face or in the neck during the first two months of palsy, and its prognostic value, was also assessed. We also investigated how study design and choice of analysis method affect the rate of facial recovery. Furthermore, the agreement between the Sunnybrook, House-Brackmann and Yanagihara facial grading systems was evaluated. From May 2001 to September 2007, a prospective, randomised, double-blind, placebo-controlled, multicentre trial with 12-month follow-up was performed in patients with Bell's palsy. Of 839 randomised patients, 829 were included in the intention-to-treat analysis; 206 received placebo plus placebo, 210 prednisolone plus placebo, 207 valaciclovir plus placebo, and 206 prednisolone plus valaciclovir. Time to recovery was significantly shorter in the 416 patients who received prednisolone compared with the 413 who did not (p<0.0001). At 12 months, 300 of 416 patients (72%) in the prednisolone group had recovered compared with 237 of 413 patients (57%) in the no prednisolone group (p<0.0001). Valaciclovir was not found to affect time to facial recovery or outcome at 12 months. Prednisolone and/or valaciclovir did not affect the incidence or intensity of pain. Presence of pain at day 11 to 17 indicated a worse prognosis for facial recovery at 12 months. We also found that recovery rates in a Bell's palsy trial are substantially affected by the choice of analysis method and definition of facial recovery. We used weighted Kappa statistics in 100 examinations of patients with facial palsy to assess the agreement between the Sunnybrook, House-Brackmann and Yanagihara scales. The highest agreement was found between the regional Sunnybrook and Yanagihara scales. An evaluative difference between the Sunnybrook and House-Brackmann systems was observed.
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| 2. |
- Bergström, Göran, 1964, et al.
(författare)
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Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
- 2021
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Ingår i: Circulation. - Philadelphia : American Heart Association. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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| 3. |
- Bergström, Göran, et al.
(författare)
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Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
- 2021
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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| 4. |
- Engström, Gunnar, et al.
(författare)
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The Swedish CArdioPulmonary BioImage Study : objectives and design
- 2015
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 278:6, s. 645-659
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Tidskriftsartikel (refereegranskat)abstract
- Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.
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| 5. |
- Lewin, Nongnit, et al.
(författare)
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Single Nucleotide Polymorphism and Cancer Risk, Tumour Recurrence, or Survival of Head and Neck Cancer Patients
- 2017
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Ingår i: Oncology. - : S. Karger AG. - 0030-2414 .- 1423-0232. ; 92, s. 161-169
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This paper aims at studying the influence of single-nucleotide polymorphisms (SNPs) on cancer risk, tumor recurrence, and survival in head and neck (H&N) cancer patients. Methods: A total of 45 SNPs in 41 genes were investigated. A total of 174 Caucasian H&N cancer patients and 245 healthy blood donors were enrolled in the study. Results: Ten SNPs were associated with H&N cancer risk, but the identified SNPs differed among males and females. Some of the SNPs were related to immune response genes. The immune response gene SNPs were also related to survival. In particular, we noted that the tumor necrosis factor alpha (TNFα) rs1800629 could have an influence on cancer risk, tumor recurrence as well as survival. Conclusion: Genetic variation of the TNFα rs1800629 might be useful as a biomarker in clinical decision-making since it was found to be related to cancer risk, tumor recurrence, and survival of H&N cancer patients.
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| 6. |
- Ahlsén, Bertil, et al.
(författare)
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Ombyggnad Torslanda
- 1990
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Consumer report for the company in question (the Volvo Automobile Company and the Volvo Torslanda plant) which is financed by the company and partly also by a research foundation. It is a matter of a work that in this particular case were carried out during nine years in a number of experimental workshops located outside the Chalmers University of Technology. These workshops were financed by the Volvo Automobile and Truck companies. This achievement, as the final contribution to the Swedish automotive industry after having already treated this research field/problem area for more than two decades before this particular period if time (involving several junior and senior research competencies, as well as industrial and governmental foundings).
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| 7. |
- Akner, Gunnar, 1953-, et al.
(författare)
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Vi står gärna bakom en utfallsbaserad vård
- 2017
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Ingår i: Dagens Samhälle. - 1652-6511.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Jörgen Nordenström försöker få det till att vår kritik av värdebaserad vård egentligen handlar om att vi vill ha mer resurser. Han har helt missuppfattat oss, skriver 26 specialistläkare i en replik.
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| 8. |
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| 9. |
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| 10. |
- Alopaeus, Tea, et al.
(författare)
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Med de nya svenska klimatmålen i sikte : Gapanalys samt strategier och förutsättningar för att nå etappmålen 2030 med utblick mot 2045
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Under våren 2017 presenterade Naturvårdsverket scenarier för hur växthusgasutsläppen i Sverige skulle kunna utvecklas till 2035. Sedan Naturvårdsverket presenterade scenarierna har ett nytt klimatpolitiskt ramverk för Sverige beslutats av riksdagen med nya klimatmål till 2030, 2040 och 2045. Regeringen har även presenterat ett antal nya styrmedel i budgetpropositionen.Naturvårdsverket ska inom miljömålssystemet löpande och strategiskt analysera och utvärdera styrmedel och åtgärder. Naturvårdsverket har mellan maj och november 2017 gjort en första uppföljning mot de nya klimatmålen. I denna rapport presenteras hur beslutade och planerade styrmedel kan komma att falla ut givet olika antagande. En översiktlig analys av styrmedel görs också.Arbetsgruppens sammansättning har varierat över tid. Sammantaget har följande personer på Naturvårdsverket deltagit i arbetsgruppen: Tea Alopaeus (projektledare), Björn Boström, Mats Björsell, Martin Boije, Joanna Dickinson, Dag Henning, Daniel Engström Stenson, Eva Jernbäcker (projektledare till september), Julien Morel, Miriam Münnich Vass, Karl-Anders Stigzelius, Ulrika Svensson, Per Wollin.Stockholm 29 november 2017Björn RisingerGeneraldirektör
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| 11. |
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| 12. |
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| 13. |
- Araujo-Cabarcas, Juan Carlos, 1981-
(författare)
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Reliable hp finite element computations of scattering resonances in nano optics
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Eigenfrequencies are commonly studied in wave propagation problems, as they are important in the analysis of closed cavities such as a microwave oven. For open systems, energy leaks into infinity and therefore scattering resonances are used instead of eigenfrequencies. An interesting application where resonances take an important place is in whispering gallery mode resonators.The objective of the thesis is the reliable and accurate approximation of scattering resonances using high order finite element methods. The discussion focuses on the electromagnetic scattering resonances in metal-dielectric nano-structures using a Drude-Lorentz model for the description of the material properties. A scattering resonance pair satisfies a reduced wave equationand an outgoing wave condition. In this thesis, the outgoing wave condition is replaced by a Dirichlet-to-Neumann map, or a Perfectly Matched Layer. For electromagnetic waves and for acoustic waves, the reduced wave equation is discretized with finite elements. As a result, the scattering resonance problem is transformed into a nonlinear eigenvalue problem.In addition to the correct approximation of the true resonances, a large number of numerical solutions that are unrelated to the physical problem are also computed in the solution process. A new method based on a volume integral equation is developed to remove these false solutions.The main results of the thesis are a novel method for removing false solutions of the physical problem, efficient solutions of non-linear eigenvalue problems, and a new a-priori based refinement strategy for high order finite element methods. The overall material in the thesis translates into a reliable and accurate method to compute scattering resonances in physics and engineering.
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| 14. |
- Axelsson, Sara, et al.
(författare)
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Bell's palsy : the effect of prednisolone and/or valaciclovir versus placebo in relation to baseline severity in a randomised controlled trial
- 2012
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Ingår i: Clinical Otolaryngology. - : Wiley. - 1749-4478 .- 1365-2273 .- 1749-4486. ; 37:4, s. 283-290
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To evaluate the treatment effect of prednisolone and/or valaciclovir in Bells palsy patients with different baseline severity of palsy.Design: Patient data were collected from the Scandinavian Bells Palsy Study, a prospective, randomised, double-blind, placebo-controlled, multi-centre trial.Setting: Sixteen otorhinolaryngological centres in Sweden and one in Finland.Participants: Altogether, 829 patients aged 1875 years were treated within 72 h of palsy onset. Patients were randomly assigned to treatment with prednisolone plus placebo (n = 210), valaciclovir plus placebo (n = 207), prednisolone plus valaciclovir (n = 206), placebo plus placebo (n = 206). Follow-up was 12 months.Main outcome measures: Facial function was assessed using the Sunnybrook grading scale at baseline and at 12 months. Complete recovery was defined as Sunnybrook score = 100.Results: All patients, regardless of baseline severity, showed significantly higher complete recovery rates if treated with prednisolone compared with no prednisolone. In patients with severe palsy, recovery at 12 months was 51% with prednisolone treatment versus 31% without prednisolone (P = 0.02). Corresponding results were 68%versus 51% (P = 0.004) for moderate, and 83%versus 73% (P = 0.02) for mild palsy. In patient groups with moderate and mild palsy at baseline, significantly fewer prednisolone-treated patients had synkinesis at 12 months (P = 0.04 and P < 0.0001, respectively). For patients with severe palsy at baseline, prednisolone versus no prednisolone made no significant difference regarding synkinesis at 12 months. Valaciclovir did not add any significant effect to prednisolone regarding recovery rate or synkinesis at 12 months.Conclusion: Prednisolone treatment resulted in higher complete recovery rates, regardless of severity at baseline. Prednisolone treatment should be considered in all patients irrespective of degree of palsy.
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| 15. |
- Axelsson, Sara, et al.
(författare)
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Prednisolone in Bell's Palsy Related to Treatment Start and Age
- 2011
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Ingår i: Otology and Neurotology. - 1531-7129 .- 1537-4505. ; 32:1, s. 141-146
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate if treatment start and age are related to the outcome in Bell's palsy patients treated with prednisolone. Study Design: Prospective, randomized, double-blind, placebo-controlled, multicenter trial. Setting: Sixteen otorhinolaryngologic centers in Sweden and 1 in Finland. Patients: Data were collected from the Scandinavian Bell's palsy study. A total of 829 patients were treated within 72 hours of onset of palsy. Follow-up was 12 months. Intervention: Patients were randomly assigned to treatment with placebo plus placebo (n = 206), prednisolone plus placebo (n = 210), valacyclovir plus placebo (n = 207), or prednisolone plus valacyclovir (n = 206). Main Outcome Measures: Facial function was assessed with the Sunnybrook grading system, and complete recovery was defined as Sunnybrook = 100. Time from onset of palsy to treatment start was registered. Results: Patients treated with prednisolone within 24 hours and 25 to 48 hours had significantly higher complete recovery rates, 66% (103/156) and 76% (128/168), than patients given no prednisolone, 51% (77/152) and 58% (102/177) (p = 0.008 and p = 0.0003, respectively). For patients treated within 49 to 72 hours of palsy onset, there were no significant differences. Patients aged 40 years or older had significantly higher complete recovery rates if treated with prednisolone, whereas patients aged younger than 40 years did not differ with respect to prednisolone treatment. However, synkinesis was significantly less in patients younger than 40 years given prednisolone (p = 0.002). Conclusion: Treatment with prednisolone within 48 hours of onset of palsy resulted in significantly higher complete recovery rates and less synkinesis compared with no prednisolone.
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| 16. |
- Baldanzi, Gabriel, et al.
(författare)
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Accelerometer-based physical activity is associated with the gut microbiota in 8416 individuals in SCAPIS.
- 2024
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 100
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Previous population-based studies investigating the relationship between physical activity and the gut microbiota have relied on self-reported activity, prone to reporting bias. Here, we investigated the associations of accelerometer-based sedentary (SED), moderate-intensity (MPA), and vigorous-intensity (VPA) physical activity with the gut microbiota using cross-sectional data from the Swedish CArdioPulmonary bioImage Study.METHODS: In 8416 participants aged 50-65, time in SED, MPA, and VPA were estimated with hip-worn accelerometer. Gut microbiota was profiled using shotgun metagenomics of faecal samples. We applied multivariable regression models, adjusting for sociodemographic, lifestyle, and technical covariates, and accounted for multiple testing.FINDINGS: Overall, associations between time in SED and microbiota species abundance were in opposite direction to those for MPA or VPA. For example, MPA was associated with lower, while SED with higher abundance of Escherichia coli. MPA and VPA were associated with higher abundance of the butyrate-producers Faecalibacterium prausnitzii and Roseburia spp. We observed discrepancies between specific VPA and MPA associations, such as a positive association between MPA and Prevotella copri, while no association was detected for VPA. Additionally, SED, MPA and VPA were associated with the functional potential of the microbiome. For instance, MPA was associated with higher capacity for acetate synthesis and SED with lower carbohydrate degradation capacity.INTERPRETATION: Our findings suggest that sedentary and physical activity are associated with a similar set of gut microbiota species but in opposite directions. Furthermore, the intensity of physical activity may have specific effects on certain gut microbiota species.FUNDING: European Research Council, Swedish Heart-Lung Foundation, Swedish Research Council, Knut and Alice Wallenberg Foundation.
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| 17. |
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| 18. |
- Berg, Thomas, et al.
(författare)
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Agreement between the Sunnybrook, House-Brackmann, and Yanagihara facial nerve grading systems in Bell´s Palsy
- 2004
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Ingår i: Otology and Neurotology. - 1531-7129 .- 1537-4505. ; 25:6, s. 1020-1026
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the agreement between the Sunnybrook facial nerve grading system and the House-Brackmann and Yanagihara systems. STUDY DESIGN: Prospective clinical facial nerve grading. SETTING: Tertiary referral center. PATIENTS: One-hundred assessments, 94 in patients with Bell's palsy and 6 with herpes zoster. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: Evaluation according to the weighted regional Sunnybrook system, the gross House-Brackmann system, and the unweighted regional Yanagihara system. Weighted kappa statistics was used to measure agreement between the grading systems. RESULTS: The average weighted kappa value between the Sunny-brook, House-Brackmann, and Yanagihara grading systems was 0.65; kappa values increased temporally (but not statistically significantly) up to day 180. The highest agreement value, 0.72, was found between the Sunnybrook and Yanagihara grading systems. The weighted kappa value between the Sunnybrook and House-Brackmann systems was 0.59. In Sunnybrook gradings less than 63, there was an overlap between House-Brackmann scores of III to VI. Reliable conversion tables between the gross House-Brackmann system and the regional Sunnybrook and Yanagihara systems could not be established. CONCLUSION: The Sunnybrook system scores at the same agreement level as the House-Brackmann and Yanagihara grading systems. There is an evaluative difference between the weighted regional Sunnybrook and the gross House-Brackmann systems. Substantial agreement was found between the regional Sunnybrook and Yanagihara scales. Sunnybrook grading is easy and quick. By adding objective measurements and additional secondary defects, the Sunnybrook system can be an alternative to the other predominating grading systems.
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| 19. |
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| 20. |
- Berg, Thomas, et al.
(författare)
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Bells pares ger resttillstånd hos 30 procent av vuxna patienter - Tidig behandling med kortison ökar utläkningen.
- 2015
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Ingår i: Läkartidningen. - 0023-7205. ; 112
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Tidskriftsartikel (refereegranskat)abstract
- Bell's palsy is an acute unilateral weakness or paralysis of the face of unknown cause. The incidence of the disease is 30 individuals per 100,000 per year. It is a diagnosis of exclusion and other known causes for acute peripheral facial palsy must be ruled out. The prognosis is overall favorable and about 70% of the patients recover completely within 6 months without treatment. Recent randomized controlled Bell's palsy trials have shown that treatment with corticosteroids shortens time to recovery and improves recovery rates while antiviral treatment alone is not more effective than placebo. The combination of corticosteroids and antivirals has not been proven more effective than corticosteroids alone. We present an update of Bell's palsy in adults with focus on diagnosis, treatment and follow-up of these patients.
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| 21. |
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| 22. |
- Berg, Thomas, et al.
(författare)
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The Course of Pain in Bell's Palsy : Treatment With Prednisolone and Valacyclovir
- 2009
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Ingår i: Otology and Neurotology. - 1531-7129 .- 1537-4505. ; 30:6, s. 842-846
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the effect of prednisolone and valacyclovir on ipsilateral pain around the ear and in the face or neck in Bell's palsy. The incidence and intensity of pain during the first 2 months of palsy and its prognostic value were also assessed. Study Design: Prospective, randomized, double-blind, placebo-controlled, multicenter trial. Setting: Sixteen tertiary referral centers in Sweden and 1 in Finland. Patients: Data are part of the Scandinavian Bell's palsy study; 829 patients aged 18 to 75 years with onset of palsy within 72 hours were included. Follow-up time was 12 months. Intervention: Patients were assigned to 1 of 4 treatment arms in a factorial fashion: placebo plus placebo; prednisolone 60 mg daily for 5 days, then tapering for 5 days, plus placebo; valacyclovir 1,000 mg 3 times daily for 7 days plus placebo; or prednisolone plus valacyclovir. Main Outcome Measures: Pain was registered on a visual analog scale within 72 hours, at Days 11 to 17, 1 month, and 2 months. Facial function was assessed with the Sunnybrook and House-Brackmann systems. Results: Prednisolone and/or valacyclovir did not significantly affect the incidence or intensity of pain during the first 2 months. Pain was registered in 542 (65%) of 829 patients. At 2 months, 53 (8%) of 637 patients still reported pain. Subjects with pain at Days 11 to 17 had lower facial recovery rates at 12 months than those with no pain (p < 0.0001). Conclusion: Prednisolone and/or valacyclovir did not affect the incidence or intensity of ipsilateral pain in Bell's palsy. The incidence of pain was similar during the first 2 weeks and then decreased. Presence of pain at Days 11 to 17 indicated a worse prognosis for facial recovery.
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| 23. |
- Berg, Thomas, et al.
(författare)
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The Effect of Prednisolone on Sequelae in Bell's Palsy
- 2012
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Ingår i: Archives of Otolaryngology - Head & Neck Surgery. - 0886-4470 .- 1538-361X. ; 138:5, s. 443-447
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To study whether prednisolone reduces sequelae in Bell's palsy. Design: Prospective, randomized, double-blind, placebo-controlled, multicenter trial with 12 months of follow-up. Setting: Seventeen referral centers. Patients: In all, 829 patients aged 18 to 75 years. Interventions: Randomization within 72 hours in a factorial fashion to placebo plus placebo (n=206); prednisolone, 60 mg/d for 5 days, with the dosage then tapered for 5 days, plus placebo (n=210); valacyclovir hydrochloride, 1000 mg 3 times daily for 7 days, plus placebo (n=207); or prednisolone plus valacyclovir (n=206). Main Outcome Measures: Facial function at 12 months assessed with the Sunnybrook and House-Brackmann grading systems. Results: In 184 of the 829 patients, the Sunnybrook score was less than 90 at 12 months; 71 had been treated with prednisolone and 113 had not (P<.001). In 98 patients, the Sunnybrook score was less than 70; 33 had received prednisolone and 65 had not (P<.001). The difference between patients who received prednisolone and who did not in House-Brackmann gradings higher than I and higher than II was also significant (P<.001 and P=.01, respectively). No significant difference was found between patients who received prednisolone and those who did not in Sunnybrook scores less than 50 (P=.10) or House-Brackmann grades higher than III (P=.80). Synkinesis was assessed with the Sunnybrook score in 743 patients. Ninety-six patients had a synkinesis score more than 2, of whom 33 had received prednisolone and 63 had not (P=.001). Sixty patients had a synkinesis score more than 4, of whom 22 had received prednisolone and 38 had not (P=.005). Conclusion: Prednisolone significantly reduces mild and moderate sequelae in Bell's palsy.
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| 24. |
- Berg, Thomas, et al.
(författare)
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The Effect of Study Design and Analysis Methods on Recovery Rates in Bell's Palsy
- 2009
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Ingår i: The Laryngoscope. - : Wiley. - 0023-852X .- 1531-4995. ; 119:10, s. 2046-2050
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Tidskriftsartikel (refereegranskat)abstract
- Objectives/Hypothesis: We investigated how study design affects the rate of recovery in Bell's palsy. Study Design: Prospective, randomized, double-blind, placebo-controlled, multicenter trial. Methods: Data were extracted from the Scandinavian Bell's palsy study, which included 829 patients. The study design was factorial; 416 patients given prednisolone, 413 not given prednisolone, 413 patients given valacyclovir, 416 not given valacyclovir. Data were analyzed with intention-to-treat principle and complete-case analysis methods and recovery was defined as Sunnybrook score 100, House-Brackmann grade I or <= grade II at 12 months. Results: With the intention-to-treat principle and last-observation-carried-forward method (n = 829) and recovery defined as Sunnybrook 100, 300 of the 416 patients (72%) receiving prednisolone had recovered compared with 237 of the 413 (57%) who did not receive prednisolone (P < .0001). With recovery defined as House-Brackmann grade 1, the corresponding recovery rates were 324 of 416 (78%) and 266 of 413 (64%) (P < .0001). With complete-case analysis and recovery defined House-Brackmann grade I (n = 782), 335 of 389 patients (86%) given prednisolone recovered compared with 277 of 393 (70%) in the group not given prednisolone (P < .0001). With recovery defined as House-Brackmann <= grade II (n = 797), the corresponding recovery rates were 380 of 396 (96%) and 353 of 401 (88%) (P < .0001). The analysis method affected the recovery rates in the valacyclovir and no-valacyclovir groups in a similar way as in the prednisolone and no-prednisolone groups. Conclusions: Recovery rates in a Bell's palsy study are substantially affected by the choice of analysis method and definition of recovery.
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| 25. |
- Bergqvist, David, et al.
(författare)
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Tumörer i glomus caroticum : en multidisciplinär angelägenhet
- 2009
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 106:20, s. 1362-1363
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Tidskriftsartikel (refereegranskat)abstract
- Carotid Body Tumours (CBT) are rare. In Sweden 1997-2006 only 28 operations were registered in the National Inpatient Registry, 2.8/year. Especially large tumours constitute a surgical challenge. This paper reports on the Uppsala experience of treating these tumours. Principles for diagnosis and treatment are discussed. A centralization is suggested.
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| 26. |
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| 27. |
- Boman, Anton, et al.
(författare)
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Isotopic variations of Fe and Zn in Finnish acid sulfate soils
- 2010
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Ingår i: Proceedings of the 19th World Congress of Soil Science. - 9780646537832 ; , s. 1-4
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Konferensbidrag (refereegranskat)abstract
- The use of a Neptune high-resolution MC-ICP-MS (Thermo Fisher Scientific) in this study has enabled high precision measurements of Fe and Zn isotopic ratios in Finnish acid sulfate soils in one near shore area (Vassor) and one inland area (Rintala).
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| 28. |
- Boström, Cecilia, et al.
(författare)
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Design proposal of electrical system for linear generator wave power plants
- 2009
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Ingår i: 35TH ANNUAL CONFERENCE OF IEEE INDUSTRIAL ELECTRONICS. - : IEEE. - 9781424446483 - 9781424446506 ; , s. 4180-4185
-
Konferensbidrag (refereegranskat)abstract
- This paper describes an electrical system layout for a wave power plant connecting linear generators to the grid. The electrical power out from the wave energy converters must be converted before they can be connected to the grid. The conversion is carried out in marine substations that will be placed on the seabed.The paper presents experimental power data from a wave energy converter that has been in operation at the Lysekil research site since March 2006. Moreover, results and analyses from experiments and simulations from tests with the generator connected to a rectifier and filter are presented. A simulation is made to show the difference between having the generator connected to a linear load and a nonlinear load, which would be the case when the generator is connected to the grid.
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| 29. |
- Botling, Johan, et al.
(författare)
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Impact of thawing on RNA integrity and gene expression analysis in fresh frozen tissue
- 2009
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Ingår i: Diagnostic molecular pathology (Print). - 1052-9551 .- 1533-4066. ; 18:1, s. 44-52
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Tidskriftsartikel (refereegranskat)abstract
- Biobanks of fresh, unfixed human tissue represent a valuable source for gene expression analysis in translational research and molecular pathology. The aim of this study was to evaluate the impact of thawing on RNA integrity and gene expression in fresh frozen tissue specimens. Portions of snap frozen tonsil tissue, unfixed or immersed in RNAlater, were thawed at room temperature for 0 minute, 5 minutes, 30 minutes, 45 minutes, 1 hour, 3 hours, 6 hours, and 16 hours before RNA extraction. Additionally, tonsil tissue underwent repetitive freezing and thawing cycles. RNA integrity was analyzed by microchip gel electrophoresis and gene expression by quantitative real-time polymerase chain reaction for selected genes (FOS, TGFB1, HIF1A, BCL2, and PCNA). Minimal RNA degradation was detected after 30 minutes of thawing in unfixed samples. This degradation was accompanied by relevant changes in gene expression for FOS and BCL2 at 45 minutes. Modified primer design or the use of different housekeeping genes could not rectify the changes for FOS. Repetitive thawing cycles had similar effects on RNA integrity. The incubation of the tissue in RNAlater efficiently prevented RNA degradation. In conclusion, degradation of RNA in frozen tissue occurs first after several minutes of thawing. Already minimal decrease in RNA quality may result in significant changes in gene expression patterns in clinical tissue samples.
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| 30. |
- Brunström, Mats, 1960-
(författare)
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Matematiska resonemang i en lärandemiljö med dynamiska matematikprogram
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall problem that formed the basis for this thesis is that students get limited opportunity to develop their mathematical reasoning ability while, at the same time, there are dynamic mathematics software available which can be used to foster this ability. The aim of this thesis is to contribute to knowledge in this area by focusing on task design in a dynamic software environment and by studying the reasoning that emerges when students work on tasks in such an environment. To analyze students’ mathematical reasoning, a new analytical tool was developed in the form of an expanded version of Toulmin’s model.Results from one of the studies in this thesis show that exploratory tasks in a dynamic software environment can promote mathematical reasoning in which claims are formulated, examined and refined in a cyclic process. However, this reasoning often displayed a lack of the more conceptual, analytic and explanatory reasoning normally associated with mathematics. This result was partly confirmed by another of the studies. Hence, one key question in the thesis has been how to design tasks that promote conceptual and explanatory reasoning. Two articles in the thesis deal with task design. One of them suggests a model for task design with a focus on exploration, explanation, and generalization. This model aims, first, to promote semantic proof production and then, after the proof has been constructed, to encourage further generalizations. The other article dealing with task design concerns the design of prediction tasks to foster student reasoning about exponential functions. The research process pinpointed key didactical variables that proved crucial in designing these tasks.
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| 31. |
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| 32. |
- Brämming, Mats, et al.
(författare)
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Characterization of Slag‐Metal Emulsion and Its Impact on Foaming Behavior and Slopping in the LD Process
- 2019
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Ingår i: Steel Research International. - : John Wiley & Sons. - 1611-3683 .- 1869-344X. ; 90:2
-
Tidskriftsartikel (refereegranskat)abstract
- In the Basic Oxygen Steelmaking (BOS) process, a heterogeneous emulsion‐solid mix will form, consisting of an emulsion of liquid slag and metal droplets, in which 2nd phase particles of undissolved fluxes and solid in‐blow precipitates are suspended. When the carbon in the metal droplets reacts with iron oxide, small bubbles of CO gas are formed. If the upward movement of these bubbles is obstructed by the physical properties of the emulsion‐solid mix, foaming will occur. Certain process conditions may lead to an excessive foam growth, in the worst case forcing foam out of the vessel. This undesired process event is known as “slopping”. Extensive studies during recent decades have shown that emulsion characteristics strongly connected to foaming are: viscosity, surface tension, and density. The extent of foaming is also dependent on bubble size; foaming increasing with smaller bubble size. However, investigations into the influence of the mineralogy and morphology of the emulsion‐solid mix on foaming in basic oxygen steelmaking are scarce. In this work, samples from trials in a 6‐tonne pilot plant BOS vessel are examined by XRD and with SEM for the determination of emulsion‐solid mix mineralogy and morphology at different stages of the oxygen blow. The study confirms the importance of tight process control in order to minimize the emulsion‐solid mix apparent viscosity and, hence, the foam height, but this without over‐oxidizing the liquid slag phase, which would result in increased gas generation within the slag‐metal emulsion.
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| 33. |
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| 34. |
- Burström, Lena, et al.
(författare)
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Improved quality and efficiency after the introduction of physician-led team triage in an emergency department.
- 2016
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 121:1, s. 38-44
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Overcrowding in the emergency department (ED) may negatively affect patient outcomes, so different triage models have been introduced to improve performance. Physician-led team triage obtains better results than other triage models. We compared efficiency and quality measures before and after reorganization of the triage model in the ED at our county hospital.MATERIALS AND METHODS: We retrospectively compared two study periods with different triage models: nurse triage in 2008 (baseline) and physician-led team triage in 2012 (follow-up). Physician-led team triage was in use during day-time and early evenings on weekdays. Data were collected from electronic medical charts and the National Mortality Register.RESULTS: We included 20,073 attendances in 2008 and 23,765 in 2012. The time from registration to physician presentation decreased from 80 to 33 min (P < 0.001), and the length of stay decreased from 219 to 185 min (P < 0.001) from 2008 to 2012, respectively. All of the quality variables differed significantly between the two periods, with better results in 2012. The odds ratio for patients who left before being seen or before treatment was completed was 0.62 (95% confidence interval 0.54-0.72). The corresponding result for unscheduled returns was 0.36 (0.32-0.40), and for the mortality rates within 7 and 30 days 0.72 (0.59-0.88) and 0.84 (0.73-0.97), respectively. The admission rate was 37% at baseline and 32% at follow-up (P < 0.001).CONCLUSION: Physician-led team triage improved the efficiency and quality in EDs.
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| 35. |
- Burström, Lena
(författare)
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Patient Safety in the Emergency Department : Culture, Waiting, and Outcomes of Efficiency and Quality
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis was to investigate patient safety in the emergency department (ED) and to determine whether this varies according to patient safety culture, waiting, and outcomes of efficiency and quality variables.I: Patient safety culture was described in the EDs of two different hospitals before and after a quality improvement project. The questionnaire “Hospital Survey on Patient Safety Culture” was used to investigate the patient safety culture. The main finding was that the staff at both hospitals scored more positively in the dimension Team-work within hospital after implementing a new work model aimed at improving patient flow and patient safety in the ED. Otherwise, we found only modest improvements.II: Grounded theory was used to explore what happens in the ED from the staff perspective. Their main concern was reducing patients’ non-acceptable waiting time. Management of waiting was improved either by increasing the throughput of patient flow by structure pushing and by shuffling patients, or by changing the experience of waiting by calming patients and by feinting to cover up.III: Three Swedish EDs with different triage models were compared in terms of efficiency and quality. The median length of stay was 158 minutes for physician-led team triage compared with 243 and 197 minutes for nurse–emergency physician and nurse–junior physician triage, respectively. Quality indicators (i.e., patients leaving before treatment was completed, the rate of unscheduled return within 24 and 72 hours, and mortality rate within 7 and 30 days) improved under the physician-led team triage.IV: Efficiency and quality variables were compared from before (2008) to after (2012) a reorganization with a shift of triage model at a single ED. Time from registration to physician decreased by 47 minutes, and the length of stay decreased by 34 minutes. Several quality measures differed between the two years, in favour of 2012. Patients leaving before treatment was completed, unscheduled return within 24 and 72 hours, and mortality rate within 7 and 30 days all improved despite the reduced admission rate.In conclusion, the studies underscore the need to improve patient safety in the ED. It is important to the patient safety culture to reduce patient waiting because it dynamically affects both patients and staff. Physician-led team triage may be a suitable model for reducing patient waiting time and increasing patient safety.
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| 36. |
- Burström, Lena, et al.
(författare)
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Physician-led team triage based on lean principles may be superior for efficiency and quality? : A comparison of three emergency departments with different triage models
- 2012
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Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : Springer Science and Business Media LLC. - 1757-7241. ; 20:1, s. 57-
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:The management of emergency departments (EDs) principally involves maintaining effective patient flow and care. Different triage models are used today to achieve these two goals. The aim of this study was to compare the performance of different triage models used in three Swedish EDs. Using efficiency and quality indicators, we compared the following triage models: physician-led team triage, nurse first/emergency physician second, and nurse first/junior physician second.METHODS: All data of patients arriving at the three EDs between 08:00- and 21:00 throughout 2008 were collected and merged into a database. The following efficiency indicators were measured: length of stay (LOS) including time to physician, time from physician to discharge, and 4-hour turnover rate. The following quality indicators were measured: rate of patients left before treatment was completed, unscheduled return within 24 and 72 hours, and mortality rate within 7 and 30 days.RESULTS: Data from 160,684 patients were analysed. The median length of stay was 158 minutes for physician-led team triage, compared with 243 and 197 minutes for nurse/emergency physician and nurse/junior physician triage, respectively (p < 0.001). The rate of patients left before treatment was completed was 3.1 % for physician-led team triage, 5.3 % for nurse/emergency physician, and 9.6 % for nurse/junior physician triage (p < 0.001). Further, the rates of unscheduled return within 24 hours were significantly lower for physician-led team triage, 1.0 %, compared with 2.1 %, and 2.5 % for nurse/emergency physician, and nurse/junior physician, respectively (p < 0.001). The mortality rate within 7 days was 0.8 % for physician-led team triage and 1.0 % for the two other triage models (p < 0.001).CONCLUSIONS: Physician-led team triage seemed advantageous, both expressed as efficiency and quality indicators, compared with the two other models.
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| 37. |
- Burström, Lena, et al.
(författare)
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The patient safety culture as perceived by staff at two different emergency departments before and after introducing a flow-oriented working model with team triage and lean principles : A repeated cross-sectional study
- 2014
-
Ingår i: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 14
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Patient safety is of the utmost importance in health care. The patient safety culture in an institution has great impact on patient safety. To enhance patient safety and to design strategies to reduce medical injuries, there is a current focus on measuring the patient safety culture. The aim of the present study was to describe the patient safety culture in an ED at two different hospitals before and after a Quality improvement (QI) project that was aimed to enhance patient safety. Methods: A repeated cross-sectional design, using the Hospital Survey On Patient Safety Culture questionnaire before and after a quality improvement project in two emergency departments at a county hospital and a university hospital. The questionnaire was developed to obtain a better understanding of the patient safety culture of an entire hospital or of specific departments. The Swedish version has 51 questions and 15 dimensions. Results: At the county hospital, a difference between baseline and follow-up was observed in three dimensions. For two of these dimensions, Team-work within hospital and Communication openness, a higher score was measured at the follow-up. At the university hospital, a higher score was measured at follow-up for the two dimensions Team-work across hospital units and Team-work within hospital. Conclusion: The result showed changes in the self-estimated patient safety culture, mainly regarding team-work and communication openness. Most of the improvements at follow-up were seen by physicians, and mainly at the county hospital.
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| 38. |
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| 39. |
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| 40. |
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| 41. |
- Carrasquilla, Germán D, et al.
(författare)
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Postmenopausal hormone therapy and risk of stroke : A pooled analysis of data from population-based cohort studies.
- 2017
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 14:11
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recent research indicates a favourable influence of postmenopausal hormone therapy (HT) if initiated early, but not late, on subclinical atherosclerosis. However, the clinical relevance of timing of HT initiation for hard end points such as stroke remains to be determined. Further, no previous research has considered the timing of initiation of HT in relation to haemorrhagic stroke risk. The importance of the route of administration, type, active ingredient, and duration of HT for stroke risk is also unclear. We aimed to assess the association between HT and risk of stroke, considering the timing of initiation, route of administration, type, active ingredient, and duration of HT.METHODS AND FINDINGS: Data on HT use reported by the participants in 5 population-based Swedish cohort studies, with baseline investigations performed during the period 1987-2002, were combined in this observational study. In total, 88,914 postmenopausal women who reported data on HT use and had no previous cardiovascular disease diagnosis were included. Incident events of stroke (ischaemic, haemorrhagic, or unspecified) and haemorrhagic stroke were identified from national population registers. Laplace regression was employed to assess crude and multivariable-adjusted associations between HT and stroke risk by estimating percentile differences (PDs) with 95% confidence intervals (CIs). The fifth and first PDs were calculated for stroke and haemorrhagic stroke, respectively. Crude models were adjusted for age at baseline only. The final adjusted models included age at baseline, level of education, smoking status, body mass index, level of physical activity, and age at menopause onset. Additional variables evaluated for potential confounding were type of menopause, parity, use of oral contraceptives, alcohol consumption, hypertension, dyslipidaemia, diabetes, family history of cardiovascular disease, and cohort. During a median follow-up of 14.3 years, 6,371 first-time stroke events were recorded; of these, 1,080 were haemorrhagic. Following multivariable adjustment, early initiation (<5 years since menopause onset) of HT was associated with a longer stroke-free period than never use (fifth PD, 1.00 years; 95% CI 0.42 to 1.57), but there was no significant extension to the time period free of haemorrhagic stroke (first PD, 1.52 years; 95% CI -0.32 to 3.37). When considering timing as a continuous variable, the stroke-free and the haemorrhagic stroke-free periods were maximal if HT was initiated approximately 0-5 years from the onset of menopause. If single conjugated equine oestrogen HT was used, late initiation of HT was associated with a shorter stroke-free (fifth PD, -4.41 years; 95% CI -7.14 to -1.68) and haemorrhagic stroke-free (first PD, -9.51 years; 95% CI -12.77 to -6.24) period than never use. Combined HT when initiated late was significantly associated with a shorter haemorrhagic stroke-free period (first PD, -1.97 years; 95% CI -3.81 to -0.13), but not with a shorter stroke-free period (fifth PD, -1.21 years; 95% CI -3.11 to 0.68) than never use. Given the observational nature of this study, the possibility of uncontrolled confounding cannot be excluded. Further, immortal time bias, also related to the observational design, cannot be ruled out.CONCLUSIONS: When initiated early in relation to menopause onset, HT was not associated with increased risk of incident stroke, regardless of the route of administration, type of HT, active ingredient, and duration. Generally, these findings held also for haemorrhagic stroke. Our results suggest that the initiation of HT 0-5 years after menopause onset, as compared to never use, is associated with a decreased risk of stroke and haemorrhagic stroke. Late initiation was associated with elevated risks of stroke and haemorrhagic stroke when conjugated equine oestrogen was used as single therapy. Late initiation of combined HT was associated with haemorrhagic stroke risk.
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| 42. |
- Cederblad, Lena, et al.
(författare)
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Cancer of the parotid gland; long-term follow-up : A single centre experience on recurrence and survival
- 2009
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 48:4, s. 549-555
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of the study was to investigate the results of treatment of malignant parotid gland tumours at a single centre during a 56 year period, focusing on tumour control and survival. PATIENTS AND METHODS: At Uppsala University Hospital, Sweden, 144 patients (73 male and 71 female) with parotid cancer were treated between 1948 and 2004. The mean and median ages were 62 and 65 years, respectively (range 16-89 years). Surgery was the primary treatment in 113 (78%) patients followed by radiotherapy in 81. Postoperative radiotherapy in doses of 64-66 Gy, where the intention was curative and delivered with either split course or not, was administered to a majority of patients after 1970. The split-course mode was practised between 1970 and 1989. The median follow-up time was 8.3 years for patients still alive. There were 57 (40%) relapses, of which 40 were local recurrences with 26 inside the treatment volume. RESULTS: The overall 5-year survival was 53%. The majority of tumour-related deaths appeared in the first 3-5 years after diagnosis. Age, co-morbidity, the presence of lymph node metastases, adenoid cystic carcinoma and extent of disease were important for outcome; gender, however, was not. We found no difference in the survival between patients following split course therapy versus continuous fractionation. No difference could be seen in the survival of patients treated in the 1970s versus the 1990s. CONCLUSIONS: Age, nodal engagement, a higher T-stage, adenoid cystic carcinoma histopathology, facial palsy and intercurrent disease worsen the outcome of patients, whereas gender does not. Treatment principles at our hospital have been surgery followed by radiotherapy since the early 1970s even though a split course technique was practised during a part of this period. Survival has not improved markedly. Thus, there is scope for improvement for this group of patients.
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| 43. |
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| 44. |
- Cederblad, Lena, et al.
(författare)
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The Combined Effects of Single-Nucleotide Polymorphisms, Tobacco Products, and Ethanol on Normal Resting Blood Mononuclear Cells
- 2013
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Ingår i: Nicotine & tobacco research. - : Oxford University Press (OUP). - 1462-2203 .- 1469-994X. ; 15:5, s. 890-895
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Tobacco and ethanol consumption are crucial factors in the development of various diseases including cancer. In this investigation, we evaluated the combined effects of a number of single nucleotide polymorphisms (SNPs), with ethanol and tobacco products on healthy individuals. Methods: Pure nicotine, cigarette smoke extract, and Swedish snuff (snus) extract were used. The effects were examined by means of in vitro cell cycle progression and cell death of peripheral blood mononuclear cells (PBMCs) obtained from healthy donors. Results: After 3 days, in vitro, resting PBMCs entered the S and G2 stage in the presence of 100 mu M nicotine. The PBMCs only proceeded to S stage, in the presence of 0.2% ethanol. The nicotine- and ethanol-induced normal cell cycle progression correlated to a number of SNPs in the IL12RB2, Rad 52, XRCC2, P53, CCND3, and ABCA1 genes. Certain SNPs in Caspases 8, IL12RB2, Rad 52, MMP2, and MDM2 genes appeared to significantly influence the effects of EtOH-, snus-, and snus + EtOH-induced cell death. Importantly, the highest degree of cell death was observed in the presence of smoke + EtOH. The amount of cell death under this treatment condition also correlated to specific SNPs, located in the MDM2, ABCA1, or GASC1 genes. Conclusions: Cigarette smoke in combination with ethanol strongly induced massive cell death. Long-term exposure to smoke and ethanol could provoke chronic inflammation, and this could be the initiation of disease including the development of cancer at various sites.
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| 45. |
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| 46. |
- Cheng, Junping, 1965-
(författare)
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Radioimmunotherapy in Experimental Head and Neck Squamous Cell Carcinoma : Tumour-targeting in vitro and in vivo
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Radioimmunotherapy (RIT) has been shown to be a practicable way to treat head and neck squamous cell carcinoma. A specific antibody recognizes the charasteristic structure of tumour cells when loaded with cytotoxic agents (toxins, drugs, radionuclides, etc). But RIT kills not only tumour cells with attached radionuclides but also adjacent tumour cells due to the “cross fire effect”. To be efficacious, RIT depends closely on suitable monoclonal antibody, on the properties of the chosen radionuclides, and on a suitable labelling method for attaching radionuclide to antibody. In this study we initially used radionuclide-labelled cMAB U36, via linker DABI in order to improve the retention of radio-conjugates in the tumour cells. Improved retention is important because the longer the radionuclide remains in tumour cells, the more effective will the tumour cells be eradicated. In the investigation, both normal mice and HNSCC-bearing nude mice were used to compare our form of treatment against other radio-iodination methods. In the biodistribution study, normal mice showed that radioactive uptake in organs diminished with time, irrespectively of whether the conjugate was directly or indirectly labelled. But in thyroid, there was a tenfold greater accumulation of direct-labelled than of indirectly labelled conjugate.In tumour-bearing nude mice, by contrast, the results showed promising uptake of radioactivity, but little uptake in direct-labelled conjugate in thyroid. Significant differences were observed on comparing tumour: organ ratios between 131I-cMAb U36 vs. 125I-DABI-cMAb U36.In the present study, cMAb U36 labelled with 211Astatine was initially used to treat HNSCC in nude mice. The biodistribution of 211At-cMAb U36 did not reveal any significant difference between an antibody-blocked group and a non-blocked group. But it did highlight the characteristics of a successful targeting conjugate in HNSCC-bearing nude mice.In the subcutaneous therapy experiment, most of the treated tumours (n=18) had disappeared by the 26th day, in both U36-blocked and non-blocked groups. Treatment in the intravenous therapy experiment had also proved effective. In the antibody non-blocked group, the smallest tumour volume was 25 mm3 (average 111 mm3) vis-á-vis 65 mm3 (average 145 mm3) in the blocked group. None of tumours grew again following treatment.
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| 47. |
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| 48. |
- Cheng, Junping, et al.
(författare)
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Radioimmunotherapy with astatine-211 using chimeric monoclonal antibody U36 in head and neck squamous cell carcinoma
- 2007
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Ingår i: The Laryngoscope. - 0023-852X .- 1531-4995. ; 117:6, s. 1013-1018
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: In advanced head and neck squamous cell carcinoma (HNSCC), there is a need for an adjuvant treatment. We aim to evaluate the biodistribution and therapeutic effect of radioimmunotherapy using the alpha emitting, astatine-211-labeled, chimeric monoclonal antibody U36 (U36) on the HNSCC cell line UT-SCC7 in vivo. STUDY DESIGN: Xenograft tumors were inoculated subcutaneously in nude mice. Astatine-211-labeled U36 was injected intravenously with or without blocking of target with nonlabeled U36. METHODS: In the biodistribution experiments, radioactivity was measured in tumors and various organs at set time points. In the therapeutic experiments, two groups (with or without blocking) received therapy, and the tumor growth was compared with that of controls. In addition, one group received nonlabeled U36 only. RESULTS: The biodistribution experiments demonstrated that astatine-211-labeled U36 could target UT-SCC7 xenografts in nude mice. With time, uptake increased in tumors and decreased in normal organs. Nonlabeled U36 did not influence tumor growth. In the two therapy groups, 18 of 20 tumors responded to therapy by decreasing or stabilizing their volumes. Significant difference was seen between the treated groups and the controls (P < .05). CONCLUSION: The study illustrates the specific binding of astatine-211-labeled U36 to HNSCC and suggests radioimmunotherapy with the alpha emitting radionuclide to be a useful treatment modality.
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| 49. |
- Cheng, Junping, et al.
(författare)
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The use of closo-dodecaborate-containing linker improves targeting of HNSCC xenografts with radioiodinated chimeric monoclonal antibody U36
- 2010
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997. ; 3:1, s. 155-160
-
Tidskriftsartikel (refereegranskat)abstract
- Radionuclide imaging of head and neck squamous cell carcinoma (HNSCC) using monoclonal antibodies (MAbs) has the potential to contribute to improved diagnosis and staging, thereby making more effective treatment possible. Chimeric monoclonal antibody U36 (cMAb U36), specific to CD44v6 antigen. is a candidate for the targeting of HNSCC. The aim of this study was to compare the influence of indirect iodination via closo-dodecaborate-based linker (DABI) with the influence of direct radioiodination on the biodistribution of the chimeric anti-CD44v6 antibody U36. The study was performed using nude mice bearing UT-SCC7 HNSCC xenografts using the paired-label method. The biodistribution of cMAb U36 labelled directly with I-131 and using DABI with I-125 was compared in the same animals. The influence of DABI on the tumour-to-organ ratio was evaluated. For both conjugates, radioactivity uptake in blood and organs decreased with time, except in tumours and the thyroid. DABI-labelled cMAb U36 was characterised by fast blood clearance and an elevated uptake in the liver and spleen. The use of DABI enabled a 1.5 to 2-fold improvement in the tumour-to-blood and tumour-to-organ ratios in comparison with direct radioiodination, with the exception of the liver and spleen. These results indicate that DABI is a promising linker for the coupling of radioiodine to HNSCC-targeting antibodies.
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| 50. |
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