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- Ragnarson Tennvall, Gunnel, et al.
(författare)
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Annual costs of treatment for venous leg ulcers in Sweden and the United Kingdom
- 2005
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Ingår i: Wound Repair and Regeneration. - : Wiley. - 1524-475X .- 1067-1927. ; 13:1, s. 13-18
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to estimate costs of treating venous leg ulcers in Sweden and the United Kingdom during 1 year and to quantify costs in different health states, The costs of treating four different types of venous leg ulcers were estimated for 52 weeks by a stochastic health economic model, which simulated resource use data obtained from prospectively collected patient data, expert panels in the two countries, and published scientific. literature, The average cost of treating an ulcer varied between E 1332 and E2585 in Sweden and from E814 to E1994 in the United Kingdom. Cost of treating large ulcers (greater than or equal to10 cm(2)) of long duration (greater than or equal to6 months) was highest in both countries. Frequency of dressing changes and duration of time for each dressing change were higher in Sweden than in the United Kingdom, resulting in higher total cost per patient in Sweden. An important factor for the total costs was time to heal. Other important variables influencing treatment costs were frequency and duration of dressing changes, Actions to reduce time used for dressing changes and the total time to healing are thus very important in reducing costs spent on treatment of venous leg ulcers in both countries.
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- Chamorro, Clara I., et al.
(författare)
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Molecular and histological studies of bladder wound healing in a rodent model
- 2020
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Ingår i: Wound Repair and Regeneration. - : Wiley. - 1067-1927 .- 1524-475X. ; 28:3, s. 293-306
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Tidskriftsartikel (refereegranskat)abstract
- The field of regenerative medicine encounters different challenges. The success of tissue-engineered implants is dependent on proper wound healing. Today, the process of normal urinary bladder wound healing is poorly characterized. We aspired to explore and elucidate the natural response to injury in an in vivo model in order to further optimize tissue regeneration in future studies. In this study, we aimed to characterize histological and molecular changes during normal healing in a rat model by performing a standardized incisional wound followed by surgical closure. We used a rodent model (n = 40) to follow the healing process in the urinary bladder for 28 days. Surgical exposure of the bladder without incision (n = 40) was performed in controls. Histological characterization and western blot analyses of proteins was carried out using specific staining and markers for inflammation, proliferation, angiogenesis, and tissue maturation. For the molecular characterization of gene expression total RNA was collected for RT2-PCR in wound healing pathway arrays. Analysis of histology revealed distinct, but overlapping, phases of healing with a local inflammatory response (days 1-8) simultaneous with a rapid formation of granulation tissue and proliferation (days 2-8). We also identified significant changes in gene expression related to inflammation, proliferation, and extracellular matrix formation. Healing of an incisional wound in a rodent urinary bladder demonstrated that all the classical phases of wound healing: hemostasis, inflammation, proliferation followed by tissue maturation were present. Our data suggest that the bladder and the skin share similar molecular signaling during wound healing, although we noted differences in the duration of each phase compared to previous studies in rat skin. Further studies will address whether our findings can be extrapolated to the human bladder.
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| 11. |
- Falk, Peter, 1962, et al.
(författare)
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Examination gloves affect secretion of matrix metalloproteinases and their inhibitors from human abdominal skin fibroblasts.
- 2003
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Ingår i: Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society. - 1067-1927. ; 11:3, s. 230-4
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Tidskriftsartikel (refereegranskat)abstract
- Overexpression of matrix metalloproteinases (MMPs) has been observed in chronic, compared to acute, wounds and altered levels might impair healing. During treatment of wounds, examination gloves are routinely used, and the wound environment thus gets exposed to gloves. The aim of this study was to characterize secretion of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in cultured fibroblasts with or without exposure to gloves. Cultures were exposed to glove washings from powdered or powder-free latex examination gloves and compared to untreated controls. MMP-1, -2, -3, -9 and their inhibitors TIMP-1 and -2 were assayed in conditioned media. Cells exposed to gloves reduced their release of MMP-1, -2, and -3 with no differences between the manufacturers of the gloves. The inhibitor TIMP-1 was reduced to 10-15% of untreated control values (p < 0.001), being less affected by the powder-free than by the powdered glove (p < 0.05). MMP-9 and TIMP-2 were not significantly altered. We therefore conclude that secretion of MMPs and TIMPs from cultured fibroblasts were affected by glove washings. Powdered and powder-free gloves had similar effects, except for a less pronounced reduction of TIMP-1 production by the powder-free glove. Examination gloves might therefore affect wound healing, with the least pronounced effect observed using the powder-free glove.
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- Gronberg, Alvar, et al.
(författare)
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Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers : a randomized, placebo-controlled clinical trial
- 2014
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Ingår i: Wound Repair and Regeneration. - : Wiley. - 1067-1927 .- 1524-475X. ; 22:5, s. 613-621
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Tidskriftsartikel (refereegranskat)abstract
- Venous leg ulcers (VLUs) are one of the most prevalent types of chronic wounds. The aim of this study was to determine the safety and dose-response efficacy of the human synthetic peptide LL-37 in the treatment of hard-to-heal VLUs. This first-in-man trial included 34 participants with VLUs and comprised a 3-week, open-label, run-in period on placebo, followed by a 4-week randomized double-blind treatment phase with twice weekly applications of LL-37 (0.5, 1.6, or 3.2 mg/mL) or placebo, and a 4-week follow-up. The healing rate constants for 0.5 and 1.6 mg/mL of LL-37 were approximately six-and threefold higher than for placebo (p = 0.003 for 0.5 mg/mL and p = 0.088 for 1.6 mg/mL). Square-root transformed wound area data showed improved healing for the 0.5 and 1.6 mg/mL dose groups compared with pretreatment values (p < 0.001 and p = 0.011, respectively). Consistently, treatment with the two lower doses markedly decreased the mean ulcer area (68% for 0.5 mg/mL and 50% for 1.6 mg/mL groups). No difference in healing was observed between the groups receiving 3.2 mg/mL of LL-37 and placebo. There were no safety concerns regarding local or systemic adverse events. In conclusion, topical treatment with LL-37 for chronic leg ulcers was safe and well tolerated with the marked effect on healing predictors at the two lower doses warranting further investigations.
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| 20. |
- Koskela, Anita, 1979-, et al.
(författare)
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Regulation of fibroblast gene expression by keratinocytes in organotypic skin culture provides possible mechanisms for the antifibrotic effect of reepithelialization
- 2010
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Ingår i: Wound Repair and Regeneration. - : The Wound Healing Society. - 1067-1927 .- 1524-475X. ; 18:5, s. 452-459
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the mechanisms behind the antifibrotic effect associated with epidermal regeneration, the expression of 12 fibroblast genes important for the modulation of the extracellular matrix (ECM), as well as alpha-smooth muscle actin, was studied in a keratinocyte-fibroblast organotypic skin culture model. The study was performed over time during epidermal generation and in the presence or absence of the profibrotic factor transforming growth factor-beta. the Presence of epidermal differentiation markers in the model was essentially coherent with that of native skin. Fibroblast gene expression was analyzed with real-time polymerase chain reaction after removal of the epidermal layer. After 2 days of air-exposed culture, 11 out of the 13 genes studied were significantly regulated by keratinocytes in the absence or presence of transforming growth factor-beta. The regulation of connective tissue growth factor, collagen I and III, fibronectin, plasmin system regulators, matrix metalloproteinases and their inhibitors as well as alpha-smooth muscle actin was consistent with a suppression of ECM formation or contraction. Overall, the results support a view that keratinocytes regulate fibroblasts to act catabolically on the ECM in epithelialization processes. This provides possible mechanisms for the clinical observations that reepithelialization and epidermal wound coverage counteract excessive scar formation.
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- Liu, Yawei, 1967-, et al.
(författare)
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Fibroblast proliferation due to exposure to a platelet concentrate in vitro is pH dependent
- 2002
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Ingår i: Wound Repair and Regeneration. - 1067-1927 .- 1524-475X. ; 10:5, s. 336-340
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Tidskriftsartikel (refereegranskat)abstract
- The influence of platelet-rich plasma lysates on fibroblast proliferation was studied in culture. Cells were exposed to platelet lysates that had been preincubated at different pHs (5.0, 7.1, and 7.6). Proliferation was evaluated with the MTT assay and incorporation of [3H]thymidine into macromolecules, while type I collagen production was assayed by Western blotting. Enzyme-linked immunosorbent assays were used to determine platelet-derived growth factor and transforming growth factor-β concentrations. Platelets preincubated in an acidic environment (pH 5.0) induced the highest degree of fibroblast proliferation, and the concentration of platelet-derived growth factor in the different treated lysates was the highest at that particular pH. The concentration of transforming growth factor-β, however, was lower after incubation at pH 5.0 than at either pH 7.1 or 7.6. These findings may be relevant to normal wound healing in vivo and useful in the treatment of wounds and delayed healing processes.
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| 25. |
- Mahlapuu, Margit, et al.
(författare)
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Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers : A multicentric prospective randomized placebo-controlled clinical trial
- 2021
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Ingår i: Wound Repair and Regeneration. - : Wiley. - 1067-1927 .- 1524-475X. ; 29:6, s. 938-950
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Tidskriftsartikel (refereegranskat)abstract
- Many patients with venous leg ulcers do not reach complete healing with compression treatment alone, which is current standard care. This clinical trial HEAL LL-37 was a phase IIb double-blind, randomized, placebo-controlled study, with the aim to evaluate the efficacy and safety of a new drug LL-37 for topical administration, in combination with compression therapy, in 148 patients suffering from hard-to-heal venous leg ulcers. The study had three arms, consisting of two groups treated with LL-37 at concentrations of 0.5 or 1.6 mg/mL, and a placebo cohort. Patients had a mean age of 67.6 years, a median ulcer duration of 20.3 months, and a mean wound size at the time of randomization of 11.6 cm(2). Efficacy analysis performed on the full study population did not identify any significant improvement in healing in patients treated with LL-37 as compared with the placebo. In contrast, a post hoc analysis revealed statistically significant improvement with LL-37 treatment in several interrelated healing parameters in the subgroup of patients with large target wounds (a wound area of at least 10 cm(2) at randomization), which is a known negative prognostic factor for healing. The study drug was well tolerated and safe in both dose strengths. In summary, this clinical trial did not detect any significant differences in healing of venous lower leg ulcers in the entire study cohort comparing patients treated with LL-37 versus placebo. A subgroup analysis provided an interesting observation that LL-37 could offer a treatment benefit in patients with large ulcers, exigently warranting a further study adequately powered to statistically assess the treatment outcome in this patient group.
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