Stem cells play a critical role in normal tissue maintenance, and mutations in these stem cells may give rise to cancer. We hypothesize that melanoma develops from a mutated stem cell and therefore residual stem cell characteristics should be able to be identified in melanoma cell lines. We studied three metastatic melanoma cell lines that exhibited multiple morphologic forms in culture and demonstrated the capacity to pigment. We used the ability to efflux Hoechst 33342 dye, a technique known to enrich for stem cells in many tissues, to segregate cell populations. The cells with the greatest ability to efflux the dye were (1) small in size, (2) had the capacity to give rise to larger cell forms, and (3) had the greatest ability to expand in culture. The small cells were found to have a decreased proliferative rate and were less melanized. Large dendritic cells that appeared to be nonproliferative were identified in cultures. Treatment with cytosine beta-D-arabinofuranoside hydrochloride (Ara-C) expanded the large cell population but the residual proliferative capacity, both in vitro and in vivo, remained concentrated in the smaller cell fraction. Antigenic staining patterns were variable and heterogeneous. Nestin (a neural stem cell marker) and gp100 (premelanosomal marker) favored the smaller cell population, while nerve growth factor receptor often labeled larger cells. Morphologic and antigenic heterogeneity remained intact after clonal purification. These findings are consistent with the behavior expected for a tumor based on stem cell biology; this finding has diagnostic and therapeutic implications for melanocytic neoplasias.
Ordering prompts for TTEs initially minimally reduced the number of TTEs ordered and increased BNP measurement at a single institution, but the effect on TTEs ordered was likely insignificant from a utilisation standpoint and decayed over time.
Background Systematic surveillance for venous thromboembolism (VTE) in the United States has been recommended by several organizations. Despite adoption of electronic medical records (EMRs) by most health care providers and facilities, however, systematic surveillance for VTE is not available.
Objectives This article develops a comprehensive, population-based surveillance strategy for VTE in a defined geographical region.
Methods The primary surveillance strategy combined computerized searches of the EMR with a manual review of imaging data at the Duke University Health System in Durham County, North Carolina, United States. Different strategies of searching the EMR were explored. Consolidation of results with autopsy reports (nonsearchable in the EMR) and with results from the Durham Veterans' Administration Medical Center was performed to provide a comprehensive report of new VTE from the defined region over a 2-year timeframe.
Results Monthly searches of the primary EMR missed a significant number of patients with new VTE who were identified by a separate manual search of radiology records, apparently related to delays in data entry and coding into the EMR. Comprehensive searches incorporating a location-restricted strategy were incomplete due to the assigned residence reflecting the current address and not the address at the time of event. The most comprehensive strategy omitted the geographic restriction step and identified all patients with VTE followed by manual review of individual records to remove incorrect entries (e.g., outside the surveillance time period or geographic location; no evidence for VTE). Consolidation of results from the EMR searches with results from autopsy reports and the separate facility identified additional patients not diagnosed within the Duke system.
Conclusion We identified several challenges with implementing a comprehensive VTE surveillance program that could limit accuracy of the results. Improved electronic strategies are needed to cross-reference patients across multiple health systems and to minimize the need for manual review and confirmation of results.
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