Demonstration of endothelial adhesion of sickle cells in vivo: a distinct role for deformable sickle cell discocytes.

Different morphologic and density classes of sickle cells (SS) may play distinct roles in the generation of vasoocclusion, explaining the complexity of this phenomena. The densest SS red blood cells (RBCs) (SS4) can induce vasoocculsion in ex vivo microcirculatory preparations as well as in an intact animal model. Previous studies of the interaction of SS deformable discocytes with endothelial monolayers or the rat ex vivo mesocecum preparation have shown adhesion that is desmopressin (dDAVP)-stimulated, von Willebrand factor (vWF)-mediated, and limited to the small venules. However, in vivo adhesion of SS RBCs to the endothelium has neither been demonstrated nor characterized; and, in particular, the relation of adhesion to vasoocclusion is unknown. Using an intact animal model that involves injecting saline-washed, density-defined SS RBCs into the femoral artery of a rat, we find that: (1) Quantitative studies of RBCs retained in the rat thigh using 99mTc-labeled RBCs and gamma camera imaging showed that dDAVP induces a threefold increase in retention of normal (AA) cells and deformable SS discocytes (SS2). (2) electron microscopy and Microfil injection show that the retention of SS2 cells is due to adhesion to the vascular endothelium with no evidence of obstruction. (3) H-1 magnetic resonance imaging showed that retention of SS4 cells induced a dose-dependent increase in tissue edema (presumable secondary to tissue hypoxia), while retention of AA or SS2 cells produced no change. We conclude that endothelial adhesion of deformable SS discocytes can be demonstrated in an in vivo animal model, that this adhesion is enhanced by dDAVP (presumably related to, but not necessarily limited to the release of vWF), and that this phenomenon per se does not lead to vasoocclusion. Nevertheless, adhesion of deformable SS discocytes may have consequences. We hypothesize that adhesion of SS discocytes could narrow the lumen of postcapillary venules and facilitate secondary trapping of SS4 cells and lead to subsequent vasoocclusion.     

Serological tests in leprosy. The sensitivity, specificity and predictive value of ELISA tests based on phenolic glycolipid antigens, and the implications for their use in epidemiological studies

This paper examines the sensitivity and specificity of two ELISA assays for IgM antibodies to Mycobacterium leprae, one employing natural phenolic glycolipid and the other employing a synthetic disaccharide glycoconjugate as antigen. Estimates of sensitivity and specificity are derived, based on a panel of sera from leprosy cases in Malawi and various non-leprosy controls from the UK. Though both assays were able to identify a high proportion of multibacillary patients, neither was able to detect a high proportion of paucibacillary patients without considerable loss of specificity. The implications of the inverse relationship between sensitivity and specificity are discussed with reference to the predictive value of such tests in such areas as Malawi, where the large majority of cases are paucibacillary.     

Use of ambulance dispatch data as an early warning system for communitywide influenzalike illness,New York City

In 1998, the New York City Department of Health and the Mayor’s Office of Emergency Management began monitoring the volume of ambulance dispatch calls as a surveillance tool for biologic terrorism. We adapted statistical techniques designed to measure excess influenza mortality and applied them to outbreak detection using ambulance dispatch data. Since 1999, we have been performing serial daily regressions to determine the alarm threshold for the current day. In this article, we evaluate this approach by simulating a series of 2,200 daily regressions. In the influenza detection implementation of this model, there were 71 (3.2%) alarms at the 99% level. Of these alarms, 64 (90%) occurred shortly before or during a period of peak influenza in each of six influenza seasons. In the bioterrorism detection implementation of this methodology, after accounting for current influenza activity, there were 24 (1.1%) alarms at the 99% level. Two occurred during a large snowstorm, 1 is unexplained, and 21 occurred shortly before or during a period of peak influenza activity in each of six influenza seasons. Our findings suggest that this surveillance system is sensitive to communitywide respiratory outbreaks with relatively few false alarms. More work needs to be done to evaluate the sensitivity of this approach for detecting nonrespiratory illness and more localized outbreaks.