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Sökning: WFRF:(Åman J.)

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  • Dalin, Frida, et al. (författare)
  • Clinical and immunological characteristics of autoimmune addison disease : A nationwide swedish multicenter study
  • 2017
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - Oxford University Press. - 0021-972X. ; 102:2, s. 379-389
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Studies of the clinical and immunological features of autoimmune Addison disease (AAD) are needed to understand the disease burden and increased mortality. Objective: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles, and cardiovascular risk factors. Design, Setting, and Participants: A cross-sectional, population-based study that included 660 AAD patients from the Swedish Addison Registry (2008-2014). When analyzing the cardiovascular risk factors, 3594 individuals from the population-based survey in Northern Sweden, MONICA (monitoring of trends and determinants of cardiovascular disease), served as controls. Main Outcome Measures: The endpoints were the prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined. Results: The proportion of 21-hydroxylase autoantibody-positive patients was 83%, and 62% of patients had ≥1 associated autoimmune diseases, more frequently coexisting in females (P < 0.0001). AAD patients had a lower body mass index (P < 0.0001) and prevalence of hypertension (P = 0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of the patients, with a mean dose of 28.1 ± 8.5 mg/d. The mean hydrocortisone equivalent dose normalized to the body surface was 14.8±4.4 mg/m2/d. A greater hydrocortisone equivalent dose was associated with a greater incidence of hypertension (P = 0.046). Conclusions: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients did not have an increased prevalence of overweight, hypertension, type 2 diabetes mellitus, or hyperlipidemia. However, high glucocorticoid replacement doses could be a risk factor for hypertension.
  • de Graaff, M. A., et al. (författare)
  • Establishment and characterization of a new human myxoid liposarcoma cell line (DL-221) with the FUS-DDIT3 translocation
  • 2016
  • Ingår i: Laboratory Investigation. - 0023-6837. ; 96:8, s. 885-894
  • Tidskriftsartikel (refereegranskat)abstract
    • Myxoid liposarcoma has the pathognomonic fusion oncogene FUS-DDIT3 encoding a chimeric transcription factor. Metastatic risk is higher with an increased round cell component and has been linked to aberrations involving the IGFR/PI3K/AKT pathway. These molecular insights have yet to translate to targeted therapies, and the lack of experimental models is a major hindrance. We describe the initial in-depth characterization of a new cell line (DL-221) and establishment of a mouse xenograft model. The cell line DL-221 was derived from a metastatic pleural lesion showing myxoid and round cell histology. This newly established cell line was characterized for phenotypic properties and molecular cytogenetic profile, using PCR, COBRA-FISH, and western blot. Next-generation whole-exome sequencing was performed to further characterize the cell line and the parent tumor. NOD-SCID-IL2R gamma knockout mice were xenograft hosts. DL-221 cells grew an adhering monolayer and COBRA-FISH showed an aneuploid karyotype with t(12;16) (q13;p11) and several other rearrangements; RT-PCR demonstrated a FUS-DDIT3 fusion transcript type 1. Both the cell line and the original tumor harbored a TP53 compound heterozygous mutation in exon 4 and 7, and were wild-type for PIK3CA. Moreover, among the 1254 variants called by whole-exome sequencing, there was 77% concordance between the cell line and parent tumor. The recently described hotspot mutation in the TERT promoter region in myxoid liposarcomas was also found at C228T in DL-221. Xenografts suitable for additional preclinical studies were successfully established in mice after subcutaneous injection. The established DL-221 cell line is the only published available myxoid liposarcoma cell line that underwent spontaneous immortalization, without requiring SV40 transformation. The cell line and its xenograft model are unique and helpful tools to study the biology and novel potential-targeted treatment approaches for myxoid liposarcoma.
  • Ivarsson, S-A, et al. (författare)
  • Prevalence of coeliac disease in Turner syndrome
  • 1999
  • Ingår i: Acta Pædiatrica. - Wiley-Blackwell Publishing Ltd. - 1651-2227. ; 88:9, s. 933-936
  • Tidskriftsartikel (refereegranskat)abstract
    • This study was undertaken to investigate the prevalence of coeliac disease in children and adolescents with Turner syndrome. Eighty-seven children and adolescents with Turner syndrome were screened for IgA- antiendomysium antibodies (EMA) and IgA-antigliadin antibodies (AGA), 5% (4/87) being found to be EMA-positive, and 15% (13/87) to have AGA levels above normal. Of the 10 patients who were either AGA- or EMA-positive and further investigated with intestinal biopsy, four manifested villous atrophy (i.e. all three of the EMA-positive patients, but only one of the seven AGA- positive patients). The results suggest EMA-positivity to be a good immunological marker for use in screening for coeliac disease, and such screening to be justified in patients with Turner syndrome.
  • Cameron, F. J., et al. (författare)
  • Are family factors universally related to metabolic outcomes in adolescents with Type 1 diabetes?
  • 2008
  • Ingår i: Diabetic Medicine. - 0742-3071 .- 1464-5491. ; 25:4, s. 463-468
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>AIMS: To assess the importance of family factors in determining metabolic outcomes in adolescents with Type 1 diabetes in 19 countries.</p> <p>METHODS: Adolescents with Type 1 diabetes aged 11-18 years, from 21 paediatric diabetes care centres, in 19 countries, and their parents were invited to participate. Questionnaires were administered recording demographic data, details of insulin regimens, severe hypoglycaemic events and number of episodes of diabetic ketoacidosis. Adolescents completed the parental involvement scale from the Diabetes Quality of Life for Youth--Short Form (DQOLY-SF) and the Diabetes Family Responsibility Questionnaire (DFRQ). Parents completed the DFRQ and a Parental Burden of Diabetes score. Glycated haemoglobin (HbA(1c)) was analysed centrally on capillary blood.</p> <p>RESULTS: A total of 2062 adolescents completed a questionnaire, with 2036 providing a blood sample; 1994 parents also completed a questionnaire. Family demographic factors that were associated with metabolic outcomes included: parents living together (t = 4.1; P &lt; 0.001), paternal employment status (F = 7.2; d.f. = 3; P &lt; 0.001), parents perceived to be over-involved in diabetes care (r = 0.11; P &lt; 0.001) and adolescent-parent disagreement on responsibility for diabetes care practices (F = 8.46; d.f. = 2; P &lt; 0.001). Although these factors differed between centres, they did not account for centre differences in metabolic outcomes, but were stronger predictors of metabolic control than age, gender or insulin treatment regimen.</p> <p>CONCLUSIONS: Family factors, particularly dynamic and communication factors such as parental over-involvement and adolescent-parent concordance on responsibility for diabetes care appear be important determinants of metabolic outcomes in adolescents with diabetes. However, family dynamic factors do not account for the substantial differences in metabolic outcomes between centres </p>
  • Hanås, Ragnar, 1951-, et al. (författare)
  • Indwelling catheters used from the onset of diabetes decrease injection pain and pre-injection anxiety
  • 2002
  • Ingår i: J Pediatr. - 0022-3476 .- 0022-3476. ; 140:3, s. 315-20
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To investigate the use of indwelling catheters as injection aids at diabetes onset to reduce injection pain and pre-injection anxiety. STUDY DESIGN: Forty-one patients aged 8.1 +/- 3.7 years (range, 1-15) participated in this open, controlled randomized study. A 10-cm VAS with faces was used for scoring. A local anesthetic cream was used before all insertions. The control group used insulin pens with standard needles. After one week, the indwelling catheter group could choose regular injections but were included in the "intention to treat" analysis. RESULTS: Injection pain and anxiety decreased from day 1 to 15 in both groups (average, 4.1 injections/day). Pain was significantly lower for indwelling catheter injections when scored by parents (median, 1.2 cm vs 2.7 cm; P =.002), children/teenagers (0.8 cm vs 1.5 cm; P =.006), and nurses (1.4 cm vs 3.0 cm; P =.002). Parental pre-injection anxiety was also lower (1.2 cm vs 2.9 cm; P =.016). Taking injections, including inserting catheters, was found to be less problematic with an indwelling catheter (1.6 cm vs 3.3 cm;P =.009). During the 6-month follow-up, injection pain and injection problems were significantly lower in the catheter group. Mean catheter indwelling time was 3.7 days. Median pain for catheter insertion was 2.1 cm and for glucose testing was 0.9 cm. Sixteen of 20 patients continued to use indwelling catheters after 2 weeks, and 9 of 20 after 6 months. CONCLUSIONS: We found an evident relief of pre-injection anxiety and injection pain when using indwelling catheters for introducing insulin injections at the onset of diabetes.
  • Sanjeevi, Carani B., et al. (författare)
  • The risk conferred by HLA-DR and DQ for type 1 diabetes in 0-35-year age group are different in different regions of Sweden
  • 2008
  • Ingår i: Annals of the New York Academy of Sciences. - 0077-8923 .- 1749-6632. ; 1150, s. 106-11
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>HLA DR4-DQ8 and DR3-DQ2 haplotypes account for 89% of newly diagnosed cases of type 1 diabetes (T1D) in Sweden. The presence of a single copy of DQ6 confers protection. The aim of the present study is to evaluate whether the risk conferred by high risk HLA DR and DQ to T1D is similar in all regions of Sweden and see whether there are any significant regional differences. The subjects comprised 799 consecutively diagnosed T1D patients and 585 age-, sex-, and geography-matched healthy controls in the age group 0-35 years. HLA typing for high-risk haplotypes was previously performed using PCR-SSOP and RFLP. The results showed that HLA DR3-DR4 gave an odds ratio of 8.14 for the whole of Sweden. However, when the study group was divided into six geographical regions, subjects from Stockholm had the highest OR, followed by those from Lund, Linköping, Gothenburg, Umeå, and Uppsala. Absolute protection was conferred by the presence of DQ6 in subjects from the Linköping region, but varied in the other regions. The frequency of DR3 and DQ2, DR4 and DQ8, DR15, and DQ6 in patients showed high linkage for each region, but were different between regions. In conclusion: The risk conferred by high-risk HLA varies in different regions for a homogenous population in Sweden. The results highlight the important role played by the various environmental factors in the precipitation of T1D.</p>
  • Sun, Chengjun, et al. (författare)
  • CRYAB-650 C&gt;G (rs2234702) affects susceptibility to type 1 diabetes and IAA-positivity in Swedish population
  • 2012
  • Ingår i: Human Immunology. - Elsevier. - 0198-8859 .- 1879-1166. ; 73:7, s. 759-766
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>BACKGROUND:</strong> Single nucleotide polymorphisms (SNPs) in the promoter region of CRYAB gene have been associated with in multiple sclerosis. CRYAB gene, which encodes alpha B-crystallin (a member of small heat shock protein), was reported as a potential autoimmune target. In this study we investigated whether SNPs in the promoter region of CRYAB gene were also important in the etiology of Type 1 diabetes (T1D).</p><p><strong>METHODS:</strong> Genotyping of SNPs in the promoter region of CRYAB gene was performed in a Swedish cohort containing 444 T1D patients and 350 healthy controls. Three SNPs were included in this study: CRYAB-652 A&gt;G (rs762550), -650 C&gt;G (rs2234702) and -249 C &gt; G (rs14133). Two SNPs (CRYAB-652 and -650) were not included in previous genome wide association studies.</p><p><strong>RESULTS:</strong> CRYAB-650 (rs2234702)*C allele was significantly more frequent in patients than in controls (OR = 1.48, Pc = 0.03). CRYAB-650*C allele was associated with IAA positivity (OR = 8.17, Pc &lt; 0.0001) and IA-2A positivity (OR = 2.14, Pc = 0.005) in T1D patients. This association with IAA was amplified by high-risk HLA carrier state (OR = 10.6, P &lt; 0.0001). No association was found between CRYAB-650 and other autoantibody positivity (GADA and ICA). CRYAB haplotypes were also associated with IAA and IA-2A positivity (highest OR = 2.07 and 2.11, respectively), these associations remain in high HLA-risk T1D patients.</p><p><strong>CONCLUSIONS:</strong> CRYAB-650 was associated with T1D in the Swedish cohort we studied. CRYAB-650*C allele might confers susceptibility to the development of T1D. CRYAB-650 was also associated with the development of IAA-positivity in T1D patients, especially in those carrying T1D high-risk HLA haplotypes.</p>
  • Albertsson-Wikland, Kerstin, et al. (författare)
  • Dose-Dependent Effect of Growth Hormone on Final Height in Children with Short Stature without Growth Hormone Deficiency
  • 2008
  • Ingår i: Journal of Clinical Endocrinology & Metabolism. - 0021-972X. ; 93:11, s. 4342-50
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Effect of GH therapy in short non GH deficient children, especially idiopathic short stature (ISS) has not been clearly established owing to lack of controlled trials until final height (FH). Objective: To investigate the effect of two GH doses compared with untreated controls on growth to FH in short children mainly with ISS. Design and Setting: A randomized, controlled, long-term multicenter trial in Sweden. Intervention: Two doses of GH (Genotropin): 33 or 67 microg/kg/d plus untreated controls. Subjects: 177 subjects with short stature were enrolled. Of these, 151 were included in the Intent to Treat (AllITT) Population and 108 in the Per Protocol (AllPP) Population. Analysis of ISS subjects included 126 children in the ITT (ISSITT) Population and 68 subjects in the PP (ISSPP) Population. Main Outcome Measures: FH SDS, difference in SDS to midparenteral height (diff MPHSDS), and gain in HeightSDS. Results: After 5.9+/-1.1 yr on GH therapy, the FHSDS in the AllPP Population treated with GH vs. controls was -1.5+/-0.81 (33 microg/kg/d: -1.7+/-0.70, 67 microg/kg/d: -1.4+/-0.86; P<0.032), vs. -2.4+/-0.85 (P<0.001), the diff MPHSDS -0.2+/-1.0 vs. -1.0+/-0.74 (P<0.001), and the gain in HeightSDS 1.3+/-0.78 vs. 0.2+/-0.69 (P<0.001). GH therapy was safe and had no impact on time to onset of puberty. A dose-response relationship identified after 1 yr remained to FH for all growth outcome variables in all four populations. Conclusion: GH treatment significantly increased FH in ISS children in a dose-dependent manner, with a mean gain of 1.3 SDS (8 cm), and a broad range of response from no gain to 3 SDS compared to a mean gain of 0.2 SDS in the untreated controls.
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