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Sökning: WFRF:(Backdahl J)

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  • Aarum, S, et al. (författare)
  • Operation for primary hyperparathyroidism: the new versus the old order. A randomised controlled trial of preoperative localisation
  • 2007
  • Ingår i: Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society. - : SAGE Publications. - 1457-4969. ; 96:1, s. 26-30
  • Tidskriftsartikel (refereegranskat)abstract
    • In patients with primary hyperparathyroidism (PHPT), parathyroid imaging is nowadays routinely used for the purpose to perform a focused unilateral minimally invasive operation. The outcome of this new strategy has, however, not been established in randomised trials. Material and Methods: Patients were randomised to either preoperative localisation with sestamibi scintigraphy and ultrasonography (group I) or no preoperative localisation (group II). In group I, a minimally invasive parathyroidectomy was performed in patients in whom both localisation studies were consistent with a single pathological gland, whereas a conventional bilateral neck exploration was performed in cases with negative localisation findings. In group II all patients underwent conventional bilateral neck exploration. Primary outcome measure was normocalcaemia at 6 months postoperatively. Results: In the preoperative localisation group (group I) 23/50 (46%) of the patients could be operated on with the focused operation whereas 26/50 (52%) were operated on by bilateral neck exploration. All patients in the no localisation group (group II; n=50) were operated on with the intended bilateral neck operation. Normocalcaemia was obtained in 96% and 94% in group I and II, respectively. Total (localisation and operative) costs were 21% higher in group I. Conclusions: Routine preoperative localisation, with the intention to perform minimally invasive parathyroidectomy, is not cost effective if concordant results of scintigraphy and ultrasonography are a prerequisite for the focused operation. Less than half of the patients were successfully managed with this strategy, at a higher cost and without obtaining a more favourable clinical outcome.
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  • Mileti, E, et al. (författare)
  • Human White Adipose Tissue Displays Selective Insulin Resistance in the Obese State
  • 2021
  • Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 70:7, s. 1486-1497
  • Tidskriftsartikel (refereegranskat)abstract
    • Selective hepatic insulin resistance is a feature of obesity and type 2 diabetes. Whether similar mechanisms operate in white adipose tissue (WAT) of those with obesity and to what extent these are normalized by weight loss are unknown. We determined insulin sensitivity by hyperinsulinemic euglycemic clamp and insulin response in subcutaneous WAT by RNA sequencing in 23 women with obesity before and 2 years after bariatric surgery. To control for effects of surgery, women postsurgery were matched to never-obese women. Multidimensional analyses of 138 samples allowed us to classify the effects of insulin into three distinct expression responses: a common set was present in all three groups and included genes encoding several lipid/cholesterol biosynthesis enzymes; a set of obesity-attenuated genes linked to tissue remodeling and protein translation was selectively regulated in the two nonobese states; and several postobesity-enriched genes encoding proteins involved in, for example, one-carbon metabolism were only responsive to insulin in the women who had lost weight. Altogether, human WAT displays a selective insulin response in the obese state, where most genes are normalized by weight loss. This comprehensive atlas provides insights into the transcriptional effects of insulin in WAT and may identify targets to improve insulin action.
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  • Backdahl, J., et al. (författare)
  • Long-Term Improvement in Aortic Pulse Wave Velocity After Weight Loss Can Be Predicted by White Adipose Tissue Factors
  • 2018
  • Ingår i: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 31:4, s. 450-457
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND Arterial stiffness, measured by pulse wave velocity (PWV), is linked to obesity, cardiovascular disease, and all-cause mortality. Short-term weight loss improves PWV, but the long-term effects are unknown. We investigated the effect of pronounced long-term weight loss on PWV and whether anthropometric/metabolic parameters and/or white adipose tissue (WAT) phenotype could predict this change in PWV. Eighty-two obese subjects were examined before and 2 years after Roux-en-Y gastric bypass. Analyses included anthropometrics, routine clinical chemistry, and hyperinsulinemic-euglycemic clamp. Arterial stiffness was measured as aortic PWV (aPWV) using the Arteriograph device. WAT mass and distribution were assessed by dual-X-ray absorptiometry. Baseline visceral and subcutaneous WAT samples were obtained to measure adipocyte cell size. Transcriptomic profiling of subcutaneous WAT was performed in a subset of subjects (n = 30). At the 2-year follow-up, there were significant decreases in body mass index (39.4 +/- 3.5 kg/m(2) vs. 26.6 +/- 3.4 kg/m(2); P < 0.0001) and aPWV (7.8 +/- 1.5 m/s vs. 7.2 +/- 1.4 m/s; P = 0.006). Multiple regression analyses showed that baseline subcutaneous adipocyte volume was associated with a reduction in aPWV (P = 0.014), after adjusting for confounders. Expression analyses of 52 genes implicated in arterial stiffness showed that only one, COL4A1, independently predicted improvements in aPWV after adjusting for confounders (P = 0.006). Bariatric surgery leads to long-term reduction in aPWV. This improvement can be independently predicted by subcutaneous adipocyte volume and WAT COL4A1 expression, which suggests that subcutaneous WAT has a role in regulating aPWV.
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  • Hogling, DE, et al. (författare)
  • Metabolic Impact of Body Fat Percentage Independent of Body Mass Index in Women with Obesity Remission After Gastric Bypass
  • 2020
  • Ingår i: Obesity surgery. - : Springer Science and Business Media LLC. - 1708-0428 .- 0960-8923. ; 30:3, s. 1086-1092
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/ObjectiveBody mass index (BMI) is central when evaluating treatment effect after gastric bypass. The metabolic impact of BMI-independent differences in body fat percentage (BF%) after gastric bypass is not fully understood. We compared metabolic and adipose tissue characteristics in women with high versus low BF% independent of BMI after obesity remission following gastric bypass.Subjects/MethodsA cohort of 215 women was included at baseline. A total of 166 women were re-examined 2 years after gastric bypass, whereof 130 had obesity remission (BMI < 30 kg/m2). Anthropometric parameters, blood pressure, and lipids were measured. Total and regional body fat mass was determined by dual-energy X-ray absorptiometry. Insulin sensitivity was assessed by homeostasis model assessment of insulin resistance (HOMA-IR) and hyperinsulinemic euglycemic clamp (Mvalue). Adipocyte size and number were determined.ResultsOf the 130 women with obesity remission, 64 had BF% ≥ 35 and 65 < 35. Independent of BMI, high BF% were associated with higher HOMA-IR (P = 0.021), lowerMvalue (P = 0.0046), higher triglycerides (P = 0.013), higher visceral/total and android/gynoid fat mass ratios (P = 0.0032 and 0.0003 respectively), and larger subcutaneous fat cell volume (P < 0.0001) 2 years after gastric bypass. No differences in anthropometric measures, glucose, blood pressure, or fat cell number were observed.ConclusionsIndependent of BMI, patients with higher BF% displayed lower insulin sensitivity, higher triglyceride levels, central fat distribution, and larger subcutaneous adipocytes 2 years after gastric bypass. Thus, determination of BF% provides additional information of metabolic characteristics at follow-up of non-obese patients after gastric bypass.
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  • Kjellman, P, et al. (författare)
  • Predictors of outcome in patients with papillary thyroid carcinoma
  • 2006
  • Ingår i: European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. - : Elsevier BV. - 0748-7983. ; 32:3, s. 345-352
  • Tidskriftsartikel (refereegranskat)
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  • Norin, U., et al. (författare)
  • Endophilin A2 deficiency protects rodents from autoimmune arthritis by modulating T cell activation
  • 2021
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The introduction of the CTLA-4 recombinant fusion protein has demonstrated therapeutic effects by selectively modulating T-cell activation in rheumatoid arthritis. Here we show, using a forward genetic approach, that a mutation in the SH3gl1 gene encoding the endocytic protein Endophilin A2 is associated with the development of arthritis in rodents. Defective expression of SH3gl1 affects T cell effector functions and alters the activation threshold of autoreactive T cells, thereby leading to complete protection from chronic autoimmune inflammatory disease in both mice and rats. We further show that SH3GL1 regulates human T cell signaling and T cell receptor internalization, and its expression is upregulated in rheumatoid arthritis patients. Collectively our data identify SH3GL1 as a key regulator of T cell activation, and as a potential target for treatment of autoimmune diseases. The autoimmune disorder, rheumatoid arthritis (RA), has been associated with multiple pathophysiological factors. Here the authors show that deficiency in endophilin A2 in rodents protects them from experimental arthritis by altering T cell activation threshold and effector functions, thereby hinting a potential target for RA therapy.
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