High-affinity pan-specific monoclonal antibodies that target cysteinyl leukotrienes and show efficacy in an acute model of colitis.

Cysteinyl leukotrienes (CysLTs) are a small family of biological signaling lipids produced by active leukocytes that contribute to diverse inflammatory disease states as a consequence of their engagement with dedicated G protein-coupled receptors. Immunization of mice with a CysLT-modified hapten carrier protein yielded novel monoclonal antibodies that display variable binding affinity to CysLTs. Solution binding assays indicated differing specificities among the antibodies tested, with antibody 10G4 displaying a preference for leukotriene C4 (LTC4). X-ray crystallography of a humanized 10G4 Fab fragment in complex with LTC4 revealed that binding induces a hook-like conformation within the hydrocarbon tail of the lipid arachidonic acid moiety. Specific hydrogen bonding to the LTC4 carboxylate groups further stabilized the complex, while a water molecule mediated a hydrogen bond network that connected the N-terminal arm of l-glutathione to both the arachidonyl carboxylate of LTC4 and the antibody heavy chain. Prophylactic administration of two anti-CysLT antibodies in mice followed by challenge with LTC4 demonstrated their in vivo efficacy against acute inflammation in a vascular permeability model. 10G4 ameliorated the effects of acute dextran sulfate sodium-induced colitis, suggesting that anti-CysLT antibodies could provide a therapeutic benefit in the treatment of inflammatory diseases.

At-a-glance monitoring: covert observations of anesthesiologists in the operating room.

BACKGROUND: Patient monitoring displays are designed to improve patient safety, and yet little is known about how anesthesiologists interact with these displays. Previous studies of clinician behavior used an observer in the operating room, which may have altered behavior. We describe a covert observation technique to determine how often and for how long anesthesiologists actually look at the monitoring display during different segments of the maintenance phase of anesthesia, and to determine whether this changed with more than 1 anesthesia provider or during concomitant activities such as reading. METHODS: Five staff anesthesiologists, 2 anesthesia fellows, 3 anesthesia residents, and 2 medical students were covertly videotaped across 10 dual anesthesia provider cases and 10 solo cases. Videotapes were later segmented (5 minutes postinduction [early maintenance], mid-maintenance, and immediately before the drapes came down [late maintenance]) and coded for looking behavior at the patient monitor, anesthesia chart, and other reading material. RESULTS: Anesthesiologists looked at the monitor in 1- to 2-second glances, performed frequently throughout the 3 segments of maintenance anesthesia. Overall, the patient monitor was looked at only 5 of the analyzed time, which is less than has previously been reported. Monitoring behavior was constant across the segments of maintenance anesthesia and was not significantly affected by the number of anesthesia providers or role (trainee vs. senior). In contrast, charting behavior and other reading material viewing changed significantly over the analyzed segments of maintenance anesthesia. CONCLUSIONS: The presence of "at-a-glance monitoring" has implications for the design of patient monitoring displays. Displays should be developed to optimize the information obtained from brief glances at the monitor.

Total intravenous anesthesia and spontaneous respiration for airway endoscopy in children--a prospective evaluation.

INTRODUCTION: Inhalational anesthesia with spontaneous respiration is traditionally used to facilitate airway endoscopy in children. The potential difficulties in maintaining adequate depth of anesthesia using inhalational anesthesia and the anesthetic pollution of the surgical environment are significant disadvantages of this technique. We report our institutional experience using total intravenous anesthesia (TIVA) and spontaneous respiration. METHODS: We prospectively studied 41 pediatric patients undergoing 52 airway endoscopies and airway surgeries. Following induction of anesthesia, a propofol infusion was titrated to a clinically adequate level of anesthesia, guided by the Bispectral Index (BIS), and a remifentanil infusion was titrated to respiratory rate. ECG, BP, pulse oximetry, BIS level, transcutaneous CO(2) (TcCO(2)), respiratory rate, and drug infusion rates were recorded. Adverse events and the response to these events were also recorded. RESULTS: Forty-one children underwent 52 airway procedures; 17 rigid bronchoscopies and 35 micro-laryngobronchoscopies, including 18 LASER treatments, were performed. The mean (sd) age was 6.9 (5.8) years and weight 26.9 (21.2) kg. The mean induction time was 13 (6) min, and anesthesia duration was 49 (30) min. The mean highest TcCO(2) recorded during the procedures was 62.8 +/- 15.3 mmHg. Coughing occurred in 14 (27%) patients, requiring additional topical anesthesia (3), a bolus of propofol (4) or remifentanil (1), or removal of the bronchoscope (1). Desaturation below 90% occurred in 10 (19%) cases; only three required intervention in the form of temporary assisted ventilation (2) or inhaled bronchodilators (1). No laryngospasm, stridor, or arrhythmias were observed. CONCLUSION: TIVA and spontaneous respiration is an effective technique to manage anesthesia for airway endoscopy and surgery in children.

A human factors and survey methodology-based design of a web-based adverse event reporting system for families.

PURPOSE: Adverse event reporting systems allow healthcare institutions to detect and prevent recurrence of avoidable patient harm. It is known that standard reporting systems, which are initiated by clinicians, detect only a minority of chart-documented adverse events. The objective of the study was to develop a web-based system, the Family Reporting System (FRS), to elicit adverse event reports from families of children admitted to hospital through survey methodology and human factors engineering techniques. MEASUREMENTS: Face validity and usability were measured via standardized survey instruments. Utility was measured via the rate, typology, degree of harm, likelihood of recurrence, quality of information, and inter-rater agreement analysis of the reported events. RESULTS: The FRS has good face validity, excellent usability, and good clinical utility. CONCLUSION: The application of survey and human factors methodologies to the design of an electronic system is an effective means of developing an electronic adverse event reporting system for the use of families of pediatric patients.