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- Ho, J. E., et al.
(författare)
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Clinical and genetic correlates of growth differentiation factor 15 in the community
- 2012
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 58:11, s. 1582-1591
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Growth differentiation factor 15(GDF15), a stress-responsive cytokine produced in cardiovascular cells under conditions of inflammation and oxidative stress, is emerging as an important prognostic marker in individuals with and without existing cardiovascular disease (CVD). We therefore examined the clinical and genetic correlates of circulating GDF15 concentrations, which have not been investigated collectively. METHODS: Plasma GDF15 concentrations were measured in 2991 participants in the Framingham Offspring Study who were free of clinically overt CVD (mean age, 59 years; 56% women). Clinical correlates of GDF15 were examined in multivariable analyses. We then conducted a genomewide association study of the GDF15 concentration that included participants in the Framingham Offspring Study and participants in the PIVUS (Prospective Investigation of the Vasculature in Uppsala Seniors) study. RESULTS: GDF15 was positively associated with age, smoking, antihypertensive treatment, diabetes, worse kidney function, and use of nonsteroidal antiinflammatory drugs (NSAIDs), but it was negatively associated with total cholesterol and HDL cholesterol. Clinical correlates accounted for 38% of interindividual variation in the circulating GDF15 concentration, whereas genetic factors accounted for up to 38% of the residual variability (h 2 = 0.38; P = 2.5 X 10 -11). We identified 1 locus of genomewide significance. This locus, which is on chromosome 19p13.11 and includes the GDF15 gene, is associated with GDF15 concentration (smallest P = 2.74 X 10 -32 for rs888663). Conditional analyses revealed 2 independent association signals at this locus (rs888663 and rs1054564), which were associated with altered cis gene expression in blood cell lines. CONCLUSIONS: In ambulatory individuals, both cardiometabolic risk factors and genetic factors play important roles in determining circulating GDF15 concentrations and contribute similarly to the overall variation.
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- Bringman, S., et al.
(författare)
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Three-year results of a randomized clinical trial of lightweight or standard polypropylene mesh in Lichtenstein repair of primary inguinal hernia
- 2006
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 93:9, s. 1056-1059
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Tidskriftsartikel (refereegranskat)abstract
- Background: This randomized trial examined whether lightweight (LW) polypropylene mesh (large pore size, partially absorbable) could have long-term benefits in reducing chronic pain and inflammation after inguinal hernia repair. Methods: Six hundred men with a primary unilateral inguinal hernia were randomized to Lichtenstein repair using a standard polypropylene mesh or a LW mesh in one of six centres. The patients were blinded to which mesh they received. Clinical examination was performed and a pain questionnaire completed 3 years after surgery. Results: Of the 590 men who had surgery, 243 (82.7 percent) of 294 in the standard mesh group and 251 (84.8 per cent) of 296 in the LW mesh group were examined in the clinic, a median of 37 (range 30-48) months after hernia repair. There were nine recurrent hernias in each group (3.7 per cent with standard mesh and 3.6 per cent with LW mesh). Patients who had LW mesh had less pain on examination, less pain on rising from lying to sitting, fewer miscellaneous groin problems and felt the mesh less often than patients with standard mesh. Conclusion: Use of LW mesh for Lichtenstein hernia repair did not affect recurrence rates, but improved some aspects of pain and discomfort 3 years after surgery.
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