OBJECTIVE -Foot ulceration is a serious complication of diabetes, and new techniques that can predict wound healing may prove very helpful. We tested the ability of medical hyperspectral technology (HT), a novel diagnostic scanning technique that can quantify tissue oxy-and deoxyhemoglobin to predict diabetic foot ulcer healing.RESEARCH DESIGN AND METHODS -Ten type 1 diabetic patients with 21 foot ulcer sites, 13 type 1 diabetic patients without ulcers, and 14 nondiabetic control subjects were seen up to 4 times over a 6-month period. HT measurements of oxyhemoglobin (HT-oxy) and deoxyhemoglobin (HT-deoxy) were performed at or near the ulcer area and on the upper and lower extremity distant from the ulcer. An HT healing index for each site was calculated from the HT-oxy and -deoxy values.RESULTS -Hyperspectral tissue oxygenation measurements observed changes in tissue immediately surrounding the ulcer when comparing ulcers that heal and ulcers that do not heal (P Ͻ 0.001). The sensitivity, specificity, and positive and negative predictive values of the HT index for predicting healing were 93, 86, 93, and 86%, respectively, when evaluated on images taken at the first visit. Changes in HT-oxy among the three risk groups were noted for the metatarsal area of the foot (P Ͻ 0.05) and the palm (P Ͻ 0.01). Changes in HT-deoxy and the HT healing index were noted for the palm only (P Ͻ 0.05 and P Ͻ 0.01, respectively).CONCLUSIONS -HT has the capability to identify microvascular abnormalities and tissue oxygenation in the diabetic foot and predict ulcer healing. HT can assist in the management of foot ulceration. Diabetes Care 30:903-910, 2007D iabetic foot ulceration (DFU) remains a serious problem, as 15% of all diabetic patients are expected to be affected with the complication during their lifespan (1). Infected and/or ischemic DFU accounts for ϳ25% of all hospital stays among diabetic patients, while foot ulceration precedes 85% of lowerextremity amputations (2). Currently, large multicenter studies (3-5) have reported that the healing rate of DFU over a 12-to 20-week period lies between 30 and 60%. Early identification of patients who will go on to fail to heal an ulcer can be of particular help, as it can allow the physician to make the right choice of treatment between a conservative and aggressive path. Pathways can be developed to streamline patient care and to apply new, expensive therapies only in patients who need them.The evaluation of neuropathy, peripheral vascular disease, presence of infection, and the depth of the ulcer are standard procedures for the management of DFU (6). However, none of the above measurements can predict wound healing. The only method that has previously been shown to predict wound healing is the measurement of changes in the ulcer area over a 4-week period of intensive care (7). However, the positive predictive value of this technique is only 58%, while the negative predictive value is 91%. Additionally, using the measurement-of-change method requires sequential patient examination...
It has been documented that histone modifications contribute to cell fate, specification and differentiation by determining the specific gene-expression profile of an individual cell or cell lineage during development. The methylation of histone tails is a key histone modification that contributes to repressing or activating gene expression depending on methylation of specific lysines within histones. This is controlled by the interplay of specific histone demethylases and methytransfrases. Little is known about how these mechanisms act to dynamically regulate gene expression during endoderm differentiation and/or early lung development. In this study, we determined by qRT-PCR that expression of H3K27 demethylases, Jmjd3 (Kdm6b) and UTX (Kdm6a), significantly increase during ES cells differentiation into endoderm in vitro. By chromatin immunoprecipitation assays, we observed that dynamic changes in histone methylation on regulatory regions of Foxa2 and Gata6 genes, crucial transcription factors for endoderm and lung lineage differentiation. In ES cells, simultaneous enrichment of H3K4me3 and H3K27me3 showed a bivalent status around the regulatory regions of Foxa2 and Gata6 associated with very low expression levels. During ES cell differentiation, a strong decrease in H3K27me3 levels on Foxa2 and Gata6 loci is associated with significantly increased expression of these genes. Furthermore, we show that Jmjd3 or/ and UTX directly bind to the Foxa2 and Gata6 loci associated with displacement of the Ezh2. We also show that histone methylation, but not DNA methylation on Foxa2 and Gata6 promoters correlates with expression of these genes in E11.5 mouse lung epithelial vs. mesenchymal cells in vivo. Our results highlight the role of H3K27me3 demethylation regulated by Jmjd3/UTX in activating gene expression during endoderm differentiation and early lung development. This abstract is funded by: PO1 HL047049 Am J Respir Crit Care Med 185;2012:A3483 Internet address: www.atsjournals.org Online Abstracts Issue
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