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- Liu, Kui, et al.
(författare)
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Kallikrein genes are associated with lupus and glomerular basement membrane-specific antibody-induced nephritis in mice and humans
- 2009
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 119:4, s. 911-923
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Tidskriftsartikel (refereegranskat)abstract
- Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous lupus nephritis. Inbred mouse strains differ in susceptibility to anti-GBM antibody-induced and spontaneous lupus nephritis. This study sought to clarify the genetic and molecular factors that maybe responsible for enhanced immune-mediated renal disease in these models. When the kidneys of 3 mouse strains sensitive to anti-GBM antibody-induced nephritis were compared with those of 2 control strains using microarray analysis, one-fifth of the underexpressed genes belonged to the kallikrein gene family,which encodes serine esterases. Mouse strains that upregulated renal and urinary kallikreins exhibited less evidence of disease. Antagonizing the kallikrein pathway augmented disease, while agonists dampened the severity of anti-GBM antibody-induced nephritis. In addition, nephritis-sensitive mouse strains had kallikrein haplotypes that were distinct from those of control strains, including several regulatory polymorphisms,some of which were associated with functional consequences. Indeed, increased susceptibility to anti-GBM antibody-induced nephritis and spontaneous lupus nephritis was achieved by breeding mice with a genetic interval harboring the kallikrein genes onto a disease-resistant background. Finally, both human SLE and spontaneous lupus nephritis were found to be associated with kallikrein genes, particularly KLK1 and the KLK3 promoter, when DNA SNPs from independent cohorts of SLE patients and controls were compared. Collectively, these studies suggest that kallikreins are protective disease-associated genes in anti-GBM antibody-induced nephritis and lupus.
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- Price, Patricia E., et al.
(författare)
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Dressing-related pain in patients with chronic wounds : an international patient perspective
- 2008
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Ingår i: International Wound Journal. - : Wiley-Blackwell Publishing Ltd. - 1742-4801 .- 1742-481X. ; 5:2, s. 159-171
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Tidskriftsartikel (refereegranskat)abstract
- This cross-sectional international survey assessed patients' perceptions of their wound pain. A total of 2018 patients (57% female) from 15 different countries with a mean age of 68.6 years (SD = 15.4) participated. The wounds were categorised into ten different types with a mean wound duration of 19.6 months (SD = 51.8). For 2018 patients, 3361 dressings/compression systems were being used, with antimicrobials being reported most frequently (n= 605). Frequency of wound-related pain was reported as 32.2%, 'never' or 'rarely', 31.1%, 'quite often' and 36.6%, 'most' or 'all of the time', with venous and arterial ulcers associated with more frequent pain (P= 0.002). All patients reported that 'the wound itself' was the most painful location (n= 1840). When asked if they experienced dressing-related pain, 286 (14.7%) replied 'most of the time' and 334 (17.2%) reported pain 'all of the time'; venous, mixed and arterial ulcers were associated with more frequent pain at dressing change (P < 0.001). Eight hundred andtwelve (40.2%) patients reported that it took <1 hour for the pain to subside after a dressing change, for 449 (22.2%) it took 1-2 hours, for 192 (9.5%) it took 3-5 hours and for 154 (7.6%) patients it took more than 5 hours. Pain intensity was measured using a visual analogue scale (VAS) (0-100) giving a mean score of 44.5 (SD = 30.5, n= 1981). Of the 1141 who reported that they generally took pain relief, 21% indicated that they did not feel it was effective. Patients were asked to rate six symptoms associated with living with a chronic wound; 'pain' was given the highest mean score of 3.1 (n= 1898). In terms of different types of daily activities, 'overdoing things' was associated with the highest mean score (mean = 2.6, n= 1916). During the stages of the dressing change procedure; 'touching/handling the wound' was given the highest mean score of 2.9, followed by cleansing and dressing removal (n= 1944). One thousand four hundred and eighty-five (80.15%) patients responded that they liked to be actively involved in their dressing changes, 1141 (58.15%) responded that they were concerned about the long-term side-effects of medication, 790 (40.3%) of patient indicated that the pain at dressing change was the worst part of living with a wound. This study adds substantially to our knowledge of how patients experience wound pain and gives us the opportunity to explore cultural differences in more detail.
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