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51.
Cutaneous diabetic wounds greatly affect the quality of life of patients, causing a substantial economic impact on the healthcare system. The limited clinical success of conventional treatments is mainly attributed to the lack of knowledge of the pathogenic mechanisms related to chronic ulceration. Therefore, management of diabetic ulcers remains a challenging clinical issue. Within this context, reliable animal models that recapitulate situations of impaired wound healing have become essential. In this study, we established a new in vivo humanised model of delayed wound healing in a diabetic context that reproduces the main features of the human disease. Diabetes was induced by multiple low doses of streptozotocin in bioengineered human‐skin‐engrafted immunodeficient mice. The significant delay in wound closure exhibited in diabetic wounds was mainly attributed to alterations in the granulation tissue formation and resolution, involving defects in wound bed maturation, vascularisation, inflammatory response and collagen deposition. In the new model, a cell‐based wound therapy consisting of the application of plasma‐derived fibrin dermal scaffolds containing fibroblasts consistently improved the healing response by triggering granulation tissue maturation and further providing a suitable matrix for migrating keratinocytes during wound re‐epithelialisation. The present preclinical wound healing model was able to shed light on the biological processes responsible for the improvement achieved, and these findings can be extended for designing new therapeutic approaches with clinical relevance.  相似文献   
52.
Treatment of inferior turbinate hypertrophy: a randomized clinical trial   总被引:9,自引:0,他引:9  
In the past 130 years, many surgical procedures for turbinate reduction have been developed. We analyzed the long-term efficacy of 6 of these surgical techniques (turbinectomy, laser cautery, electrocautery, cryotherapy, submucosal resection, and submucosal resection with lateral displacement) over a 6-year follow-up period. We randomly divided 382 patients into 6 therapeutic groups and surgically treated them at the Department of Otorhinolaryngology of the University of Siena. After 6 years, only submucosal resection resulted in optimal long-term normalization of nasal patency and in restoration of mucociliary clearance and local secretory IgA production to a physiological level with few postoperative complications (p < .001). The addition of lateral displacement of the inferior turbinate improved the long-term results. We recommend, in spite of the greater surgical skill required, submucosal resection combined with lateral displacement as the first-choice technique for the treatment of nasal obstruction due to hypertrophy of the inferior turbinates.  相似文献   
53.
Crystal deposition in a case of cutaneous Rosai-Dorfman disease   总被引:2,自引:0,他引:2  
Rosai-Dorfman Disease (RDD) is an idiopathic reactive proliferation of distinctive histiocytes that have abundant cytoplasm and commonly exhibit intracytoplasmic ingestion of inflammatory cells (emperipolesis). The histiocytes are immunopositive for S100 protein and are typically associated with an infiltrate of lymphocytes, plasma cells, and neutrophils. The classic clinical presentation is massive enlargement of (usually) cervical lymph nodes with a histologic appearance that mimics exaggerated sinus histiocytosis. RDD can also involve extra-nodal sites and skin involvement is common either as part of disseminated disease or as a result of primary disease. We report an exceptional case of cutaneous RDD with crystal deposition in a young male presenting with skin nodules. Skin biopsy showed classic features of cutaneous RDD with the additional feature of conspicuous rhomboidal and needle-shaped crystals within the cytoplasm of many lesional plasma cells, histiocytes, and also in an extra-cellular location. The plasma cells were polyclonal by light chain immunostaining. Crystal deposition has not been reported to date in RDD and is likely a result of the reactive plasma cell proliferation.  相似文献   
54.
PURPOSE: To evaluate corneal changes and ocular aberrations during an orthokeratology test. DESIGN: A prospective, nonrandomized cohort study. METHODS: Fourteen myopic patients (26 eyes) underwent an orthokeratology fitting test with the BE contact lens (Ultravision Pty, Ltd, Brisbane, Australia). Best spectacle-corrected visual acuity (BSCVA), uncorrected (Ultravision Pty, Ltd, Brisbane, Australia) visual acuity (UCVA), subjective cycloplegic refraction, biomicroscopy, corneal topography, optical pachymetry, and aberrometry were performed at baseline and one and eight nights orthokeratology. The short-term effect of orthokeratology using corneal topography, tomography, and ocular aberrations was evaluated. RESULTS: The mean spherical equivalent changed from -2.24 +/- 0.98 diopters (D) at baseline to 0.15 +/- 0.76 D after the eight nights of lens wear (P = .001). All patients had an UCVA of 20/30, 69.2% with 20/20. Changes in central corneal pachymetry were not observed. There was a statistically significant increase in the temporal corneal thickness from night one, without any difference between nights one and eight (P > .001). A significant increase of higher-order root mean square values was observed from baseline (0.42 +/- 0.16 mum), night one (0.81 +/- 0.24 mum), and night eight (1.04 +/- 0.24 mum). Increases in coma (Z7+Z8) and spherical aberration (Z12) were observed. Positive horizontal (Z8) coma increased in right eyes, and negative horizontal (Z8) coma increased in left eyes (P < .001). CONCLUSIONS: Myopia reduction resulting from rapid central corneal flattening and improvement of UCVA occurred after orthokeratology. Higher-order aberrations (HOAs), particularly spherical aberration and coma, increased significantly during the orthokeratology test. An increase of temporal pachymetry and differences in coma direction induced between the eyes may be related to the subclinical lens decentration temporally.  相似文献   
55.
Abstract We showed the ability of human dermal fibroblasts to take up Malassezia furfur and the effect of ketoconazole and cytoskeleton inhibitors, including cytochalasin D and colchicine, on invasivity. Engulfment was evaluated by May Grunwald Giemsa stain and confirmed by acridine orange staining and electron microscopy. Both revealed the different steps of engulfment, including a fusion event between lysosomes and phagosomes containing M. furfur. Subinhibitory concentrations of ketoconazole (5 μg/ml) reduced the invasive capacity compared to controls (52.0 ± 6.3 vs 10.0 ± 1.2). M. furfur induced changes in the cytoskeleton of human dermal fibroblasts, with signs of disaggregation of actin fibres. We also studied the effect of the cytoskeleton inhibitors, cytochalasin D (1 μg/ ml) and colchicine (1 μg/ml), on engulfment. Cytochalasin D, an inhibitor of actin polymers, inhibited the uptake of M. furfur by human dermal fibroblasts. Colchicine, a microtubule inhibitor, reduced the uptake of M. furfur less markedly. This suggests that the process of engulfment is F-actin-dependent, but the integrity of microtubules is also important in “non-professional” phagocytic cells such as dermal fibroblasts. Received: 25 May 2000 / Revised: 26 January 2001 / Accepted: 12 May 2001  相似文献   
56.
OBJECTIVE: To investigate the value of serum antitissue transglutaminase IgA antibodies (IgA-TTG) and IgA antiendomysial antibodies (IgA-EMA) in the diagnosis of coeliac disease in cohorts from different geographical areas in Europe. The setting allowed a further comparison between the antibody results and the conventional small-intestinal histology. METHODS: A total of 144 cases with coeliac disease [median age 19.5 years (range 0.9-81.4)], and 127 disease controls [median age 29.2 years (range 0.5-79.0)], were recruited, on the basis of biopsy, from 13 centres in nine countries. All biopsy specimens were re-evaluated and classified blindly a second time by two investigators. IgA-TTG were determined by ELISA with human recombinant antigen and IgA-EMA by an immunofluorescence test with human umbilical cord as antigen. RESULTS: The quality of the biopsy specimens was not acceptable in 29 (10.7%) of 271 cases and a reliable judgement could not be made, mainly due to poor orientation of the samples. The primary clinical diagnosis and the second classification of the biopsy specimens were divergent in nine cases, and one patient was initially enrolled in the wrong group. Thus, 126 coeliac patients and 106 controls, verified by biopsy, remained for final analysis. The sensitivity of IgA-TTG was 94% and IgA-EMA 89%, the specificity was 99% and 98%, respectively. CONCLUSIONS: Serum IgA-TTG measurement is effective and at least as good as IgA-EMA in the identification of coeliac disease. Due to a high percentage of poor histological specimens, the diagnosis of coeliac disease should not depend only on biopsy, but in addition the clinical picture and serology should be considered.  相似文献   
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58.
HIV-1 infection is associated with serious cardiovascular complications, but the roles of HIV-1, viral proteins, and highly active antiretroviral therapy (HAART) drugs are not understood. HAART decreases the overall risk of heart disease but leads to metabolic disturbances and possibly coronary artery disease. We investigated toxicities of HIV-1, HIV-1 glycoprotein 120 (gp120), and HAART drugs for human coronary artery endothelial cells (CAECs), brain microvascular endothelial cells, and neonatal rat ventricular myocytes (NRVMs). HIV-1 and gp120, but not azidothymidine (AZT), induced apoptosis of NRVMs and CAECs. Ethylisothiourea, an inhibitor of nitric oxide synthase, inhibited apoptosis induction by gp120. AZT, HIV-1, and gp120 all damaged mitochondria of cardiomyocytes. HAART drugs, AZT, and indinavir, but not HIV-1, produced intercellular gaps between confluent endothelial cells and decreased transendothelial electrical resistance. In conclusion, HIV-1 and gp120 induce toxicity through induction of cardiomyocyte and endothelial cell apoptosis. HAART drugs disrupt endothelial cell junctions and mitochondria and could cause vascular damage.  相似文献   
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