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1.
  • Arkblad, Eva L, et al. (författare)
  • Multiplex ligation-dependent probe amplification improves diagnostics in spinal muscular atrophy
  • 2006
  • Ingår i: Neuromuscular disorders : NMD. - 0960-8966 .- 1873-2364. ; 16:12, s. 830-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Spinal muscular atrophy (SMA) is an autosomal recessive disease caused by decreased levels of survival motor neuron protein (SMN). In the majority of cases, this decrease is due to absence of the SMN1 gene. Multiplex ligation-dependent probe amplification (MLPA) is a modern quantitative molecular method. Applied in SMA cases, it improves diagnostics by simultaneously identifying the number of copies of several target sequences in the SMN1 gene and in nearby genes. Using MLPA in clinical diagnostics, we have identified a previously unreported, partial deletion of SMN1 (exons 1-6) in two apparently unrelated Swedish families. This mutation would not have been detected by conventional diagnostic methods. This paper illustrates the broad clinical and genetic spectrum of SMA and includes reports of MLPA results and clinical descriptions of a patient with homozygous absence of SMN1 and only one SMN2 (prenatal onset SMA type 1), an asymptomatic woman with five SMN2 (lacking SMN1) and representative patients with SMA types 1, 2 and 3.
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2.
  • Bratt, Ola, et al. (författare)
  • The Study of Active Monitoring in Sweden (SAMS) : A randomized study comparing two different follow-up schedules for active surveillance of low-risk prostate cancer
  • 2013
  • Ingår i: Scandinavian Journal of Urology. - : Informa Healthcare. - 2168-1805 .- 2168-1813. ; 47:5, s. 347-355
  • Forskningsöversikt (refereegranskat)abstract
    • Objective. Only a minority of patients with low-risk prostate cancer needs treatment, but the methods for optimal selection of patients for treatment are not established. This article describes the Study of Active Monitoring in Sweden (SAMS), which aims to improve those methods. Material and methods. SAMS is a prospective, multicentre study of active surveillance for low-risk prostate cancer. It consists of a randomized part comparing standard rebiopsy and follow-up with an extensive initial rebiopsy coupled with less intensive follow-up and no further scheduled biopsies (SAMS-FU), as well as an observational part (SAMS-ObsQoL). Quality of life is assessed with questionnaires and compared with patients receiving primary curative treatment. SAMS-FU is planned to randomize 500 patients and SAMS-ObsQoL to include at least 500 patients during 5 years. The primary endpoint is conversion to active treatment. The secondary endpoints include symptoms, distant metastases and mortality. All patients will be followed for 10-15 years. Results. Inclusion started in October 2011. In March 2013, 148 patients were included at 13 Swedish urological centres. Conclusions. It is hoped that the results of SAMS will contribute to fewer patients with indolent, low-risk prostate cancer receiving unnecessary treatment and more patients on active surveillance who need treatment receiving it when the disease is still curable. The less intensive investigational follow-up in the SAMS-FU trial would reduce the healthcare resources allocated to this large group of patients if it replaced the present standard schedule.
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3.
  • Bratt, Ola, et al. (författare)
  • The Value of an Extensive Transrectal Repeat Biopsy with Anterior Sampling in Men on Active Surveillance for Low-risk Prostate Cancer: A Comparison from the Randomised Study of Active Monitoring in Sweden (SAMS)
  • 2019
  • Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 76:4, s. 461-466
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A systematic repeat biopsy is recommended for men starting on active surveillance for prostate cancer, but the optimal number and distribution of cores are unknown. Objective: To evaluate an extensive repeat transrectal biopsy with anterior sampling in men starting on active surveillance. Design, setting, and participants: Randomised multicentre trial. From 2012 to 2016, 340 Swedish men, aged 40-75 yr, with recently diagnosed low-volume Gleason grade group 1 prostate cancer were included. Intervention: Either an extensive transrectal biopsy with anterior sampling (median 19 cores) or a standard transrectal biopsy (median 12 cores). Outcome measurements and statistical analysis: Primary outcome measure: Gleason grade group >= 2 cancer. Secondary outcomes: Cancer in anteriorly directed biopsy cores and postbiopsy infection. Nonparametric statistical tests were applied. Results and limitations: Gleason grade group >= 2 cancer was detected in 16% of 156 men who had an extensive biopsy and in 10% of 164 men who had a standard biopsy, a 5.7% difference (95% confidence interval [CI]-0.2% to 13%, p = 0.09). There was a strong linear association between prostate-specific antigen (PSA) density and cancer in the anteriorly directed biopsy cores. The odds ratios for cancer in the anteriorly directed cores were for any cancer 2.2 (95% CI 1.3-3.9, p = 0.004) and for Gleason grade group >= 2 cancer 2.3 (95% CI 1.2-4.4, p = 0.015) per 0.1-ng/ml/cm(3) increments. Postbiopsy infections were equally common in the two groups. A limitation is that magnetic resonance imaging was not used. Conclusions: The trial did not support general use of the extensive transrectal repeat biopsy template, but cancer in the anteriorly directed cores was common, particularly in men with high PSA density. The higher the PSA density, the stronger the reason to include anterior sampling at a systematic repeat biopsy. Patient summary: This trial compared two different templates for transrectal prostate biopsy in men starting on active surveillance for low-risk prostate cancer. Cancer was often found in the front part of the prostate, which is not sampled on a standard prostate biopsy. (C) 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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4.
  • Johansson, Ewa, 1964, et al. (författare)
  • Long-term quality-of-life outcomes after radical prostatectomy or watchful waiting: the Scandinavian Prostate Cancer Group-4 randomised trial.
  • 2011
  • Ingår i: The lancet oncology. - : Elsevier. - 1474-5488 .- 1470-2045.
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: For men with localised prostate cancer, surgery provides a survival benefit compared with watchful waiting. Treatments are associated with morbidity. Results for functional outcome and quality of life are rarely reported beyond 10 years and are lacking from randomised settings. We report results for quality of life for men in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) after a median follow-up of more than 12 years. METHODS: All living Swedish and Finnish men (400 of 695) randomly assigned to radical prostatectomy or watchful waiting in SPCG-4 from 1989 to 1999 were included in our analysis. An additional 281 men were included in a population-based control group matched for region and age. Physical symptoms, symptom-induced stress, and self-assessed quality of life were evaluated with a study-specific questionnaire. Longitudinal data were available for 166 Swedish men who had answered quality-of-life questionnaires at an earlier timepoint. FINDINGS: 182 (88%) of 208 men in the radical prostatectomy group, 167 (87%) of 192 men in the watchful-waiting group, and 214 (76%) of 281 men in the population-based control group answered the questionnaire. Men in SPCG-4 had a median follow-up of 12·2 years (range 7-17) and a median age of 77·0 years (range 61-88). High self-assessed quality of life was reported by 62 (35%) of 179 men allocated radical prostatectomy, 55 (34%) of 160 men assigned to watchful waiting, and 93 (45%) of 208 men in the control group. Anxiety was higher in the SPCG-4 groups (77 [43%] of 178 and 69 [43%] of 161 men) than in the control group (68 [33%] of 208 men; relative risk 1·42, 95% CI 1·07-1·88). Prevalence of erectile dysfunction was 84% (146 of 173 men) in the radical prostatectomy group, 80% (122 of 153) in the watchful-waiting group, and 46% (95 of 208) in the control group and prevalence of urinary leakage was 41% (71 of 173), 11% (18 of 164), and 3% (six of 209), respectively. Distress caused by these symptoms was reported significantly more often by men allocated radical prostatectomy than by men assigned to watchful waiting. In a longitudinal analysis of men in SPCG-4 who provided information at two follow-up points 9 years apart, 38 (45%) of 85 men allocated radical prostatectomy and 48 (60%) of 80 men allocated watchful waiting reported an increase in number of physical symptoms; 50 (61%) of 82 and 47 (64%) of 74 men, respectively, reported a reduction in quality of life. INTERPRETATION: For men in SPCG-4, negative side-effects were common and added more stress than was reported in the control population. In the radical prostatectomy group, erectile dysfunction and urinary leakage were often consequences of surgery. In the watchful-waiting group, side-effects can be caused by tumour progression. The number and severity of side-effects changes over time at a higher rate than is caused by normal ageing and a loss of sexual ability is a persistent psychological problem for both interventions. An understanding of the patterns of side-effects and time dimension of their occurrence for each treatment is important for full patient information. FUNDING: US National Institutes of Health; Swedish Cancer Society; Foundation in Memory of Johanna Hagstrand and Sigfrid Linnér.
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5.
  • Ribom, Eva L, et al. (författare)
  • Estimation of physical performance and measurements of habitual physical activity may capture men with high risk to fall--data from the Mr Os Sweden cohort.
  • 2009
  • Ingår i: Archives of gerontology and geriatrics. - : Elsevier. - 1872-6976 .- 0167-4943. ; 49:1, s. e72-6
  • Tidskriftsartikel (refereegranskat)abstract
    • To evaluate if clinically usable estimates of physical performance and level of habitual physical activity are associated with fall risk in elderly men. A population-based sample of 3014 randomly selected men aged 69-80 years was recruited to medical centers in Gothenburg, Malmoe, or Uppsala. The level of physical activity and self-reported falls during the preceding 12 months was evaluated using a questionnaire. The physical performance ability was estimated by measurements of handgrip strength, a timed stands test, a 6-m walking test and a 20-cm narrow walk test. Falls were reported in 16.5% of the men. Fallers performed 6.2+/-19.0% (mean+/-standard deviations; S.D.) less in right handgrip measures, 8.8+/-40.6% slower in the timed stands test, 6.8+/-30.8% slower in the 6-m walking test, and 5.3+/-28.8% slower in the 20-cm narrow walk test (all p<0.001, respectively). The odds ratio for falls among men who performed <-3 S.D. or failed compared to the mean (+1 S.D. to -1 S.D.) in the timed stands test was 3.41 (95% CI 2.31-5.02; p<0.001) and 2.46 (95% CI 1.80-3.34; p<0.001) in 20-cm narrow walk test. There were more fallers that never were physical active (73.0% vs. 65.4%, p<0.001) and who were sitting more (6.4+/-2.5 h/day vs. 6.0+/-2.3 h/day, p<0.05) than among the non-fallers. Fallers scored less than non-fallers in all the estimates of physical performance and they were more sedentary in their life style. The report suggests that clinical usable tests of physical performance and evaluation of habitual physical activity in the clinical situation possibly can be used to predict risk of falls in elderly men.
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6.
  • Adnan, Ali, et al. (författare)
  • Health-related quality of life among tonsillar carcinoma patients in Sweden in relation to treatment and comparison with quality of life among the population
  • 2020
  • Ingår i: Head and Neck-Journal for the Sciences and Specialties of the Head and Neck. - : WILEY. - 1043-3074 .- 1097-0347. ; 42:5, s. 860-872
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The health-related quality of life (HRQOL) of tonsillar carcinoma survivors was explored to investigate any HRQOL differences associated with tumor stage and treatment. The survivors' HRQOL was also compared to reference scores from the population. Methods In this exploratory cross-sectional study patients were invited 15 months after their diagnosis and asked to answer two quality of life questionnaires (EORTC QLQ- C30, EORTC QLQ- HN35), 405 participated. Results HRQOL was associated with gender, with males scoring better than females on a few scales. Patients' HRQOL was more associated with treatment than tumor stage. Patients' HRQOL was worse than that in an age- and sex-matched reference group from the normal population, the largest differences were found for problems with dry mouth followed by problems with sticky saliva, senses, swallowing and appetite loss. Conclusions The tonsillar carcinoma patients had a worse HRQOL compared to the general population one year after treatment.
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7.
  • Ahlberg, Mats Steinholtz, et al. (författare)
  • PCASTt/SPCG-17-A randomised trial of active surveillance in prostate cancer: Rationale and design
  • 2019
  • Ingår i: BMJ Open. - : BMJ PUBLISHING GROUP. - 2044-6055. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Overtreatment of localised prostate cancer is substantial despite increased use of active surveillance. No randomised trials help define how to monitor patients or when to initiate treatment with curative intent. Methods and analysis A randomised, multicentre, intervention trial designed to evaluate the safety of an MRI-based active surveillance protocol, with standardised triggers for repeated biopsies and radical treatment. The aim is to reduce overtreatment of prostate cancer. 2000 men will be randomly allocated to either surveillance according to current practice or to standardised triggers at centres in Sweden, Norway, Finland and the UK. Men diagnosed in the past 12 months with prostate cancer, ≤T2a, prostate-specific antigen (PSA) <15 ng/mL, PSA density ≤0.2 ng/mL/cc, any International Society of Urological Pathology (ISUP) grade 1 are eligible. Men with ISUP grade 2 in <30% of cores on systematic biopsy and <10 mm cancer in one core on systematic or targeted biopsy are also eligible. Men diagnosed on systematic biopsy should have an MRI and targeted biopsies against Prostate Imaging and Reporting Data System V.2 3-5 lesions before inclusion. Identical follow-up in the two study arms: biannual PSA testing, yearly clinical examination and MRI every second year. In the experimental arm, standardised triggers based on MRI and PSA density elicit repeated biopsies. MRI and histopathological progression trigger radical treatment. Primary outcome measure is progression-free survival. Secondary outcome measures are cumulative incidence of metastatic disease, treatments with curative intent, pT3-4 at radical prostatectomy, switch to watchful waiting, prostate cancer mortality and quality of life. Inclusion started in October 2016 and in October 2018; 275 patients have been enrolled. Ethics and dissemination Ethical approval was obtained in each participating country. Results for the primary and secondary outcome measures will be submitted for publication in peer-reviewed journals. Trial registration number NCT02914873.
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8.
  • Ahlm, Clas, 1956-, et al. (författare)
  • Prevalence of antibodies specific to Puumala virus among farmers in Sweden
  • 1998
  • Ingår i: Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 24:2, s. 104-108
  • Tidskriftsartikel (refereegranskat)abstract
    • Serological evidence confirmed that the exposure of humans to Puumala virus is firmly restricted to the northern and central parts of Sweden. In addition the evidence indicated that, in this region, farming is associated with an increased risk of contracting hantavirus infection.
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9.
  • Apró, William, et al. (författare)
  • Leucine does not affect mechanistic target of rapamycin complex 1 assembly but is required for maximal ribosomal protein s6 kinase 1 activity in human skeletal muscle following resistance exercise.
  • 2015
  • Ingår i: The FASEB Journal. - 0892-6638 .- 1530-6860. ; 29:10, s. 4358-4373
  • Tidskriftsartikel (refereegranskat)abstract
    • We examined how the stimulatory effect of leucine on the mechanistic target of rapamycin complex 1 (mTORC1) pathway is affected by the presence of the remaining essential amino acids. Nine male subjects performed resistance exercise on 4 occasions and were randomly supplied essential amino acids (EAAs) with or without leucine (EAA-Leu), leucine alone, or flavored water (placebo; control). Muscle biopsies were taken from the vastus lateralis before and 60 and 90 min after exercise. Biopsies were analyzed for protein phosphorylation, kinase activity, protein-protein interactions, amino acid concentrations, and tracer incorporation. Leucine alone stimulated ribosomal protein s6 kinase 1 (S6K1) phosphorylation ∼280% more than placebo and EAA-Leu after exercise. Moreover, this response was enhanced by 60-75% after intake of EAAs compared with that of leucine alone (P < 0.05). Kinase activity of S6K1 reflected that of S6K1 phosphorylation; 60 min after exercise, the activity was elevated 3.3- and 4.2-fold with intake of leucine alone and with EAAs, respectively (P < 0.05). The interaction between mammalian target of rapamycin and regulatory-associated protein of mammalian target of rapamycin was unaltered in response to both resistance exercise and amino acid provision. Leucine alone stimulates mTORC1 signaling, although this response is enhanced by other EAA and does not appear to be caused by alterations in mTORC1 assembly.-Apró, W., Moberg, M., Hamilton, D. L., Ekblom, B., Rooyackers, O., Holmberg, H.-C., Blomstrand, E. Leucine does not affect mechanistic target of rapamycin complex 1 assembly but is required for maximal ribosomal protein s6 kinase 1 activity in human skeletal muscle following resistance exercise.
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10.
  • Apro, William, et al. (författare)
  • Resistance exercise-induced S6K1 kinase activity is not inhibited in human skeletal muscle despite prior activation of AMPK by high-intensity interval cycling
  • 2015
  • Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - 0193-1849 .- 1522-1555. ; 308:6, s. E470-E481
  • Tidskriftsartikel (refereegranskat)abstract
    • Combining endurance and strength training in the same session has been reported to reduce the anabolic response to the latter form of exercise. The underlying mechanism, based primarily on results from rodent muscle, is proposed to involve AMPK-dependent inhibition of mTORC1 signaling. This hypothesis was tested in eight trained male subjects who in randomized order performed either resistance exercise only (R) or interval cycling followed by resistance exercise (ER). Biopsies taken from the vastus lateralis before and after endurance exercise and repeatedly after resistance exercise were assessed for glycogen content, kinase activity, protein phosphorylation, and gene expression. Mixed muscle fractional synthetic rate was measured at rest and during 3 h of recovery using the stable isotope technique. In ER, AMPK activity was elevated immediately after both endurance and resistance exercise (similar to 90%, P < 0.05) but was unchanged in R. Thr(389) phosphorylation of S6K1 was increased severalfold immediately after exercise (P < 0.05) in both trials and increased further throughout recovery. After 90 and 180 min recovery, S6K1 activity was elevated (similar to 55 and similar to 110%, respectively, P < 0.05) and eukaryotic elongation factor 2 phosphorylation was reduced (similar to 55%, P < 0.05) with no difference between trials. In contrast, markers for protein catabolism were differently influenced by the two modes of exercise; ER induced a significant increase in gene and protein expression of MuRF1 (P < 0.05), which was not observed following R exercise only. In conclusion, cycling-induced elevation in AMPK activity does not inhibit mTOR complex 1 signaling after subsequent resistance exercise but may instead interfere with the hypertrophic response by influencing key components in protein breakdown.
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