Strains of Escherichia coli persist within the human gut as normal commensals, but are frequent pathogens and can cause recurrent infection. Here we show that, in contrast to E. coli subjected to opsonic interactions stimulated by the host's immune response, E. coli that bind to the macrophage surface exclusively through the bacterial lectin FimH can survive inside the cell following phagocytosis. This viability is largely due to the attenuation of intracellular free-radical release and of phagosome acidification during FimH-mediated internalization, both of which are triggered by antibody-mediated internalization. This different processing of non-opsonized bacteria is supported by morphological evidence of tight-fitting phagosomes compared with looser, antibody-mediated phagosomes. We propose that non-opsonized FimH-expressing E. coli co-opt internalization of lipid-rich microdomains following binding to the FimH receptor, the glycosylphosphatidylinositol-linked protein CD48, because (1) the sterol-binding agents filipin, nystatin and methyl beta-cyclodextrin specifically block FimH-mediated internalization; (2) CD48 and the protein caveolin both accumulate on macrophage membranes surrounding bacteria; and (3) antibodies against CD48 inhibit FimH-mediated internalization. Our findings bring the traditionally extracellular E. coli into the realm of opportunistic intracellular parasitism and suggest how opportunistic infections with FimH-expressing enterobacteria could occur in a setting deprived of opsonizing antibodies.

Apheresis procedures have a 150-fold higher incidence of SAEs requiring hospitalization compared to whole blood donation. Identification of donors at risk for complications can facilitate modification of the apheresis procedure in order to reduce the likelihood of adverse events. Although our study did not demonstrate a cause-effect relationship between platelet donation and the development of acute coronary syndromes, underlying cardiovascular disease was detected in 2 donors during or after the apheresis who were otherwise asymptomatic.

Although controlled biomedical terminologies have been with us for centuries, it is only in the last couple of decades that close attention has been paid to the quality of these terminologies. The result of this attention has been the development of auditing methods that apply formal methods to assessing whether terminologies are complete and accurate. We have performed an extensive literature review to identify published descriptions of these methods and have created a framework for characterizing them. The framework considers manual, systematic and heuristic methods that use knowledge (within or external to the terminology) to measure quality factors of different aspects of the terminology content (terms, semantic classification, and semantic relationships). The quality factors examined included concept orientation, consistency, non-redundancy, soundness and comprehensive coverage. We reviewed 130 studies that were retrieved based on keyword search on publications in PubMed, and present our assessment of how they fit into our framework. We also identify which terminologies have been audited with the methods and provide examples to illustrate each part of the framework.

A standard set of names and codes for laboratory test results is critical for any endeavor requiring automated data pooling, including multi-institutional research and cross-facility patient care. This need has led to the development of the logical observation identifier names and codes (LOINC) database and its test-naming convention. This study is an expansion of a pilot study using LOINC to exchange laboratory data between Columbia University Medical Center in New York and Barnes Hospital at Washington University in St. Louis, where we described complexities and ambiguities that arose in the LOINC coding process (D.M. Baorto, J.J. Cimino, C.A. Parvin, M.G. Kahn, Proc. Am. Med. Inf. Assoc. 1997). For the present study, we required the same two medical centers to again extract raw laboratory data from their local information system for a defined patient population, translate tests into LOINC and provide aggregate data which could then be used to compare laboratory utilization. Here we examine a larger number of tests from each site which have been recoded using an updated version of the LOINC database. We conclude that the coding of local tests into LOINC can often be complex, especially the 'Kind of Property' field and apparently trivial differences in choices made by individual institutions can result in nonmatches in electronically pooled data. In the present study, 75% of failures to match the same tests between different institutions using LOINC codes were due to differences in local coding choices. LOINC has the potential to eliminate the need for detailed human inspection during the pooling of laboratory data from diverse sites and perhaps even a built-in capability to adjust matching stringency by selecting subsets of LOINC fields required to match. However, a quality standard coding procedure is required and examples highlighted in this paper may require special attention while mapping to LOINC.

The Medical Entities Dictionary (MED) has served as a unified terminology at New York Presbyterian Hospital and Columbia University for more than 20 years. It was initially created to allow the clinical data from the disparate information systems (e.g., radiology, pharmacy, and multiple laboratories, etc) to be uniquely codified for storage in a single data repository, and functions as a real time terminology server for clinical applications and decision support tools. Being conceived as a knowledge base, the MED incorporates relationships among local terms, between local terms and external standards, and additional knowledge about terms in a semantic network structure. Over the past two decades, we have sought to develop methods to maintain, audit and improve the content of the MED, such that it remains true to its original design goals. This has resulted in a complex, multi-faceted process, with both manual and automated components. In this paper, we describe this process, with examples of its effectiveness. We believe that our process provides lessons for others who seek to maintain complex, concept-oriented controlled terminologies.