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Sökning: WFRF:(Ludvigsson M. L.) > (2010-2014)

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1.
  • Gyllenberg, Alexandra, et al. (författare)
  • Variability in the CIITA gene interacts with HLA in multiple sclerosis.
  • 2014
  • Ingår i: Genes and Immunity. - Nature Publishing Group. - 1476-5470. ; 15:3, s. 162-167
  • Tidskriftsartikel (refereegranskat)abstract
    • The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.Genes and Immunity advance online publication, 16 January 2014; doi:10.1038/gene.2013.71.
2.
  • Knobler, R., et al. (författare)
  • Guidelines on the use of extracorporeal photopheresis
  • 2014
  • Ingår i: Journal of the European Academy of Dermatology and Venereology. - Wiley-Blackwell. - 0926-9959. ; 28:s1, s. 1-37
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundAfter the first investigational study on the use of extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma was published in 1983 with its subsequent recognition by the FDA for its refractory forms, the technology has shown significant promise in the treatment of other severe and refractory conditions in a multi-disciplinary setting. Among the major studied conditions are graft versus host disease after allogeneic bone marrow transplantation, systemic sclerosis, solid organ transplant rejection and inflammatory bowel disease. Materials and methodsIn order to provide recognized expert practical guidelines for the use of this technology for all indications the European Dermatology Forum (EDF) proceeded to address these questions in the hands of the recognized experts within and outside the field of dermatology. This was done using the recognized and approved guidelines of EDF for this task. Results and conclusionThese guidelines provide at present the most comprehensive available expert recommendations for the use of extracorporeal photopheresis based on the available published literature and expert consensus opinion.
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4.
  • Cattaneo, A, et al. (författare)
  • Overweight and obesity in infants and pre-school children in the European Union a review of existing data
  • 2010
  • Ingår i: OBESITY REVIEWS. - Blackwell Publishing Ltd. - 1467-7881. ; 11:5, s. 389-398
  • Tidskriftsartikel (refereegranskat)abstract
    • Pandgt;The objective of this study was to synthesize available information on prevalence and time trends of overweight and obesity in pre-school children in the European Union. Retrieval and analysis or re-analysis of existing data were carried out. Data sources include WHO databases, Medline and Google, contact with authors of published and unpublished documents. Data were analysed using the International Obesity Task Force reference and cut-offs, and the WHO standard. Data were available from 18/27 countries. Comparisons were problematic because of different definitions and methods of data collection and analysis. The reported prevalence of overweight plus obesity at 4 years ranges from 11.8% in Romania (2004) to 32.3% in Spain (1998-2000). Countries in the Mediterranean region and the British islands report higher rates than those in middle, northern and eastern Europe. Rates are generally higher in girls than in boys. With the possible exception of England, there was no obvious trend towards increasing prevalence in the past 20-30 years in the five countries with data. The use of the WHO standard with cut-offs at 1, 2 and 3 standard deviations yields lower rates and removes gender differences. Data on overweight and obesity in pre-school children are scarce; their interpretation is difficult. Standard methods of surveillance, and research and policies on prevention and treatment, are urgently needed.
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5.
  • Gyllenberg, A, et al. (författare)
  • Age-dependent variation of genotypes in MHC II transactivator gene (CIITA) in controls and association to type 1 diabetes
  • 2012
  • Ingår i: Genes and Immunity. - Nature Publishing Group. - 1476-5470. ; 13:8, s. 632-640
  • Tidskriftsartikel (refereegranskat)abstract
    • The major histocompatibility complex class II transactivator (CIITA) gene (16p13) has been reported to associate with susceptibility to multiple sclerosis, rheumatoid arthritis and myocardial infarction, recently also to celiac disease at genome-wide level. However, attempts to replicate association have been inconclusive. Previously, we have observed linkage to the CIITA region in Scandinavian type 1 diabetes (T1D) families. Here we analyze five Swedish T1D cohorts and a combined control material from previous studies of CIITA. We investigate how the genotype distribution within the CIITA gene varies depending on age, and the association to T1D. Unexpectedly, we find a significant difference in the genotype distribution for markers in CIITA (rs11074932, P=4 × 10(-5) and rs3087456, P=0.05) with respect to age, in the collected control material. This observation is replicated in an independent cohort material of about 2000 individuals (P=0.006, P=0.007). We also detect association to T1D for both markers, rs11074932 (P=0.004) and rs3087456 (P=0.001), after adjusting for age at sampling. The association remains independent of the adjacent T1D risk gene CLEC16A. Our results indicate an age-dependent variation in CIITA allele frequencies, a finding of relevance for the contrasting outcomes of previously published association studies.
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7.
  • Cardwell, C R, et al. (författare)
  • Birthweight and the risk of childhood-onset type 1 diabetes: a meta-analysis of observational studies using individual patient data
  • 2010
  • Ingår i: DIABETOLOGIA. - 0012-186X. ; 53:4, s. 641-651
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated whether children who are heavier at birth have an increased risk of type 1 diabetes. Relevant studies published before February 2009 were identified from literature searches using MEDLINE, Web of Science and EMBASE. Authors of all studies containing relevant data were contacted and asked to provide individual patient data or conduct pre-specified analyses. Risk estimates of type 1 diabetes by category of birthweight were calculated for each study, before and after adjustment for potential confounders. Meta-analysis techniques were then used to derive combined ORs and investigate heterogeneity between studies. Data were available for 29 predominantly European studies (five cohort, 24 case-control studies), including 12,807 cases of type 1 diabetes. Overall, studies consistently demonstrated that children with birthweight from 3.5 to 4 kg had an increased risk of diabetes of 6% (OR 1.06 [95% CI 1.01-1.11]; p = 0.02) and children with birthweight over 4 kg had an increased risk of 10% (OR 1.10 [95% CI 1.04-1.19]; p = 0.003), compared with children weighing 3.0 to 3.5 kg at birth. This corresponded to a linear increase in diabetes risk of 3% per 500 g increase in birthweight (OR 1.03 [95% CI 1.00-1.06]; p = 0.03). Adjustments for potential confounders such as gestational age, maternal age, birth order, Caesarean section, breastfeeding and maternal diabetes had little effect on these findings. Children who are heavier at birth have a significant and consistent, but relatively small increase in risk of type 1 diabetes.
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8.
  • Lahdenperä, Anna, et al. (författare)
  • Up-regulation of small intestinal interleukin-17 immunity in untreated coeliac disease but not in potential coeliac disease or in type 1 diabetes
  • 2012
  • Ingår i: Clinical and Experimental Immunology. - John Wiley & Sons. - 0009-9104. ; 167:2, s. 226-234
  • Tidskriftsartikel (refereegranskat)abstract
    • Up-regulation of interleukin (IL)-17 in small intestinal mucosa has been reported in coeliac disease (CD) and in peripheral blood in type 1 diabetes (T1D). We explored mucosal IL-17 immunity in different stages of CD, including transglutaminase antibody (TGA)-positive children with potential CD, children with untreated and gluten-free diet-treated CD and in children with T1D. Immunohistochemistry was used for identification of IL-17 and forkhead box protein 3 (FoxP3)-positive cells and quantitative polymerase chain reaction (qPCR) for IL-17, FoxP3, retinoic acid-related orphan receptor (ROR)c and interferon (IFN)-γ transcripts. IL-1β, IL-6 and IL-17 were studied in supernatants from biopsy cultures. Expression of the apoptotic markers BAX and bcl-2 was evaluated in IL-17-stimulated CaCo-2 cells. The mucosal expression of IL-17 and FoxP3 transcripts were elevated in individuals with untreated CD when compared with the TGA-negative reference children, children with potential CD or gluten-free diet-treated children with CD (P andlt; 0·005 for all IL-17 comparisons and P andlt; 0·01 for all FoxP3 comparisons). The numbers of IL-17-positive cells were higher in lamina propria in children with CD than in children with T1D (P andlt; 0·05). In biopsy specimens from patients with untreated CD, enhanced spontaneous secretion of IL-1β, IL-6 and IL-17 was seen. Activation of anti-apoptotic bcl-2 in IL-17-treated CaCo-2 epithelial cells suggests that IL-17 might be involved in mucosal protection. Up-regulation of IL-17 could, however, serve as a biomarker for the development of villous atrophy and active CD.
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9.
  • Peolsson, A, et al. (författare)
  • Effects of neck-specific exercise with or without a behavioural approach in addition to prescribed physical activity for individuals with chronic whiplash-associated disorders: a prospective randomised study
  • 2013
  • Ingår i: BMC Musculoskeletal Disorders. - BioMed Central. - 1471-2474. ; 14:311
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Up to 50% of chronic whiplash associated disorders (WAD) patients experience considerable pain and disability and remain on sick-leave. No evidence supports the use of physiotherapy treatment of chronic WAD, although exercise is recommended. Previous randomised controlled studies did not evaluate the value of adding a behavioural therapy intervention to neck-specific exercises, nor did they compare these treatments to prescription of general physical activity. Few exercise studies focus on patients with chronic WAD, and few have looked at patients ability to return to work and the cost-effectiveness of treatments. Thus, there is a great need to develop successful evidence-based rehabilitation models. The study aim is to investigate whether neck-specific exercise with or without a behavioural approach (facilitated by a single caregiver per patient) improves functioning compared to prescription of general physical activity for individuals with chronic WAD. less thanbrgreater than less thanbrgreater thanMethods/Design: The study is a prospective, randomised, controlled, multi-centre study with a 2-year follow-up that includes 216 patients with chronic WAD (andgt;6 months and andlt;3 years). The patients (aged 18 to 63) must be classified as WAD grade 2 or 3. Eligibility will be determined with a questionnaire, telephone interview and clinical examination. The participants will be randomised into one of three treatments: (A) neck-specific exercise followed by prescription of physical activity; (B) neck-specific exercise with a behavioural approach followed by prescription of physical activity; or (C) prescription of physical activity alone without neck-specific exercises. Treatments will be performed for 3 months. We will examine physical and psychological function, pain intensity, health care consumption, the ability to resume work and economic health benefits. An independent, blinded investigator will perform the measurements at baseline and 3, 6, 12 and 24 months after inclusion. The main study outcome will be improvement in neck-specific disability as measured with the Neck Disability Index. All treatments will be recorded in treatment diaries and medical records. less thanbrgreater than less thanbrgreater thanDiscussion: The study findings will help improve the treatment of patients with chronic WAD.
10.
  • Sherry, Nicole, et al. (författare)
  • Teplizumab for treatment of type 1 diabetes (Protege study): 1-year results from a randomised, placebo-controlled trial
  • 2011
  • Ingår i: The Lancet. - Elsevier. - 0140-6736. ; 378:9790, s. 487-497
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Findings of small studies have suggested that short treatments with anti-CD3 monoclonal antibodies that are mutated to reduce Fc receptor binding preserve beta-cell function and decrease insulin needs in patients with recent-onset type 1 diabetes. In this phase 3 trial, we assessed the safety and efficacy of one such antibody, teplizumab. less thanbrgreater than less thanbrgreater thanMethods In this 2-year trial, patients aged 8-35 years who had been diagnosed with type 1 diabetes for 12 weeks or fewer were enrolled and treated at 83 clinical centres in North America, Europe, Israel, and India. Participants were allocated (2:1:1:1 ratio) by an interactive telephone system, according to computer-generated block randomisation, to receive one of three regimens of teplizumab infusions (14-day full dose, 14-day low dose, or 6-day full dose) or placebo at baseline and at 26 weeks. The Protege study is still underway, and patients and study staff remain masked through to study closure. The primary composite outcome was the percentage of patients with insulin use of less than 0.5 U/kg per day and glycated haemoglobin A(1c) (HbA(1c)) of less than 6-5% at 1 year. Analyses included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT00385697. less thanbrgreater than less thanbrgreater thanFindings 763 patients were screened, of whom 516 were randomised to receive 14-day full-dose teplizumab (n=209), 14-day low-dose teplizumab (n=102), 6-day full-dose teplizumab (n=106), or placebo (n=99). Two patients in the 14-day full-dose group and one patient in the placebo group did not start treatment, so 513 patients were eligible for efficacy analyses. The primary outcome did not differ between groups at 1 year: 19.8% (41/207) in the 14-day full-dose group; 13.7% (14/102) in the 14-day low-dose group; 20.8% (22/106) in the 6-day full-dose group; and 20.4% (20/98) in the placebo group. 5% (19/415) of patients in the teplizumab groups were not taking insulin at 1 year, compared with no patients in the placebo group at 1 year (p=0.03). Across the four study groups, similar proportions of patients had adverse events (414/417 [99%] in the teplizumab groups vs 98/99 [99%] in the placebo group) and serious adverse events (42/417 [10%] vs 9/99 [9%]). The most common clinical adverse event in the teplizumab groups was rash (220/417 [53%] vs 20/99 [20%] in the placebo group). less thanbrgreater than less thanbrgreater thanInterpretation Findings of exploratory analyses suggest that future studies of immunotherapeutic intervention with teplizumab might have increased success in prevention of a decline in beta-cell function (measured by C-peptide) and provision of glycaemic control at reduced doses of insulin if they target patients early after diagnosis of diabetes and children.
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