No abstract

Numerous concerns regarding the potential for misdiagnosis of Lyme disease using commercial assays have been voiced by the US Food and Drug Administration (FDA). We attempted to clarify the clinical value of serologic testing for Lyme disease using the results of commonly marketed assays for detecting antibody to Borrelia burgdorferi, the organism that causes Lyme disease. We reviewed published studies on B burgdorferi test performance published through 1998, package insert labeling from FDA-cleared test kits for B burgdorferi, and Lyme Disease Survey Set LY-A from the College of American Pathologists. We assessed the sensitivity and specificity of commercial serologic tests (enzyme-linked immunosorbent assay [ELISA], immunofluorescence antibody [IFA], and immunodot) for diagnosis of Lyme disease. To reduce this risk of misdiagnosis, it is important that clinicians understand the performance characteristics and limitations of these tests. These tests, in common use in clinical or commercial laboratories, should be used only to support a clinical diagnosis of Lyme disease, not as the primary basis for making diagnostic or treatment decisions. Serologic testing is not useful early in the course of Lyme disease because of the low sensitivity of tests in early disease. Serologic testing may be more useful in later disease, at which time sensitivity and specificity of the test are improved. Positive or equivocal results on an ELISA, IFA, or immunodot assay requires supplemental testing with a Western blot assay. A negative result on the Western blot or ELISA indicates that there is no serologic evidence of infection by B burgdorferi at the time the sample was drawn.

The prevalence of silent or occult silicone gel breast implant rupture is higher than was previously suspected. Most women in this study had MR imaging evidence of at least one ruptured silicone gel breast implant.

Directed cell migration is a prerequisite not only for the development of the central nervous system, but also for topically restricted, appropriate immune responses. This is crucial for host defense and immune surveillance. Attracting environmental cues guiding leukocyte cell traffic are likely to be complemented by repulsive cues, which actively abolish cell migration. One such a paradigm exists in the developing nervous system, where neuronal migration and axonal path finding is balanced by chemoattractive and chemorepulsive cues, such as the neuronal repulsive guidance molecule-A (RGM-A). As expressed at the inflammatory site, the role of RGM-A within the immune response remains unclear. Here we report that RGM-A (i) is expressed by epithelium and leukocytes (granulocytes, monocytes, and T/B lymphocytes); (ii) inhibits leukocyte migration by contact repulsion and chemorepulsion, depending on dosage, through its receptor neogenin; and (iii) suppresses the inflammatory response in a model of zymosan-A-induced peritonitis. Systemic application of RGM-A attenuates the humoral proinflammatory response (TNF-α, IL-6, and macrophage inflammatory protein 1α), infiltration of inflammatory cell traffic, and edema formation. In contrast, the demonstrated anti-inflammatory effect of RGM-A is absent in mice homozygous for a gene trap mutation in the neo1 locus (encoding neogenin). Thus, our results suggest that RGM-A is a unique endogenous inhibitor of leukocyte chemotaxis that limits inflammatory leukocyte traffic and creates opportunities to better understand and treat pathologies caused by exacerbated or misdirected inflammatory responses.