Abstract. The leukocyte integrins (CDll/CD18 or ß2-type integrins) are expressed exclusively on leukocytes and participate in many adhesion-dependent functions (Arnaout, M .A . 1990. Blood. 75 :1037-1050Springer, T. A . 1990. Nature. (Load.) 346:425-434 ; Dustin, M . L ., and T. S. Springer. 1991 . Annu. Rev. Immunol. 9:27-66) . The avidity of leukocyte integrin binding to their ligands or counter-receptors is dependent upon response to intracellular signals (Wright, S. D., and B. C. Meyer. 1986. J. Immunol. 136 :1759-1764 Dustin, M . A ., and T. S. Springer. 1989. Nature (Lond.) . 341 :619-624) . We have investigated the effects of a novel mAb (mAb 24) which defines a leukocyte integrin a subunit epitope that is Mgt+-dependent and may be used as a "reporter" of the activation state of these receptors (Dransfield, I ., and N . Hogg T HE three leukocyte integrins, lymphocyte functionassociated antigen-1 (LFA-1), complement receptor type 3 (CR3)/Mac-1, and p150,95 are heterodimeric molecules each comprising a unique a subunit noncovalently associated with a common 02 subunit (Sanchez-Madrid et al ., 1983) . The roles of these molecules in immune functions are best characterized for LFA-1(CDlla/CD18) and CR3-(CDl lb/CDl8) . Antibody blocking studies have demonstrated a key role for LFA-1 in many cellular interactions of leukocytes . CR3 is important in functions such as myeloid cell phagocytosis, adherence to activated endothelium and chemotaxis (Arnaout, 1990;Springer, 1990;Smith et al ., 1989 presented to show that this mAb inhibits monocytedependent, antigen-specific T cell proliferation and IL-2-activated natural killer cell assays which are both dependent on lymphocyte function-associated antigen-1 (LFA1), and complement receptor type 3 (CR3)-mediated neutrophil chemotaxis to f-Met-Leu-Phe . This inhibitory effect is not caused by the prevention of receptor/ligand binding because LFA-1/ICAM-1, LFA-1/ ICAM-2,3 and CR3/iC3b interactions are, under activating conditions, promoted rather than blocked by mAb 24 . As it does not interfere with mitogen-stimulated T cell proliferation, it is unlikely that mAb 24 transduces a "negative" or antiproliferative signal to the T cells to which it is bound . Using a model system of transient activation of LFA-1, we have found that mAb 24 prevents "deadhesion" of receptor/ligand pairs, possibly locking leukocyte integrins in an "active" conformation . It is speculated that inhibition of leukocyte integrin function by this mAb reflects the necessity for dynamic leukocyte integrin/ligand interactions .

The results from this study indicate that MK-383 appears to be well tolerated and active in man. It is the first nonpeptide GPIIb/IIIa antagonist that can be used to investigate the antithrombotic potential of this new class of antiplatelet agents.

Objectives: An emergency medicine (EM) clerkship can provide a medical student with a unique educational experience. The authors sought to describe the current experiential curriculum of the EM clerkship, along with methods of evaluation, feedback, and grading.Methods: A descriptive survey was utilized. Clerkship directors at EM residency programs accredited by the Accreditation Council for Graduate Medical Education completed an online questionnaire. Data were analyzed using descriptive statistics.Results: Ninety-two (70%) of 132 EM clerkship directors completed the survey. Sixty institutions (65%) accepted only fourth-year medical students, and 35% accepted both third-and fourth-year students. The median number of didactic lecture hours provided during each rotation block for students was ten (interquartile range [IQR], 6-16). The average length of a student's clinical shift was eight hours, while the median number of clinical shifts reported per rotation was 15 (IQR, 14-16). The median number of hours worked weekly by a medical student was 40 (IQR,(35)(36)(37)(38)(39)(40)(41)(42)(43). Fifty-four EM clerkship directors (59%) incorporated the Accreditation Council for Graduate Medical Education six core competencies into their evaluation process. Seventy-one clerkship directors (77%) used a shift evaluation card to evaluate the clinical performance of medical students. Fifty-four (59%) incorporated an end-of-rotation written examination to determine the final rotation grade for a medical student.Conclusions: Medical students are exposed to a variety of didactic lectures and procedure labs but have similar experiences regarding shift length and work hours. Methods of evaluation of clinical performance vary across clinical sites.ACADEMIC EMERGENCY MEDICINE 2007; 14:629-634 ª

In a search for a rapid and accurate imaging agent for scintigraphic detection of infection and inflammation, an LTB4 receptor antagonist, 99Tcm-RP517, which contains the hydrazino nicotinamide moiety, has been developed recently. To study the in vivo behaviour of 99Tcm-RP517, rabbits with Escherichia coli infection were injected intravenously with 99Tcm-RP517. Gamma camera images were obtained and ex vivo bio-distribution was determined at several hours post-injection (p.i.). In a separate set of rabbits the choledochal duct was cannulated to quantitatively monitor the hepatobiliary clearance of the radiopharmaceutical. The receptor binding fraction of the radiolabelled RP517 exceeded 70%. Accumulation of 99Tcm-RP517 in the abscess was visualized as early as 1 h p.i. Due to rapid blood clearance (t1/2 alpha=18+/-0.6 min, t1/2 beta=6.5+/-0.4 h) and high abscess uptake, the abscess-to-muscle ratios increased with time from 7.0+/-2.3 at 1 h p.i. to 44.3+/-4.6 at 20 h p.i. The agent mainly cleared via the hepatobiliary route: 50% of the radiolabel was recovered in the small bowel at 1 h p.i., whereas 85% was found in cecum and sigmoid at 20 h p.i. In conclusion, 99Tcm-RP517 rapidly visualized E. coli abscesses in rabbits. The agent rapidly cleared from the blood, mainly via the hepatobiliary route. High abscess-to-background ratios were achieved. The accumulation in the intestines could limit the applicability of this agent for detecting infectious processes in the abdominal area. The development of a more hydrophilic analogue of 99Tcm-RP517 could improve the clinical applicability of this agent.