Physiology of cold-stored platelets

Platelet transfusions are a life-saving medical intervention used for the treatment of thrombocytopenia or hemorrhage. Extensive research has gone into trying to understand how to store platelets prior to the transfusion event. Much has been learned about storage bag materials, synthetic solutions, and how temperature impacts platelet viability and function. While room temperature storage of platelets preserves 24-hour in vivo platelet recovery and survival there is a greater risk for bacterial growth. Therefore, cold storage of platelets has become attractive due to the reduction in potential bacterial proliferation and the maintenance of platelet function beyond 5 days of storage. Cold stored platelets, however, have their own set of challenges. Cold stored platelets become activated through several mechanisms. The morphological and molecular changes that occur due to cold exposure enhance their ability to participate in the hemostatic process at the cost of rapid clearance from circulation. This review focuses on the underlying mechanisms leading to cold platelet activation and the receptor modifications involved in platelet clearance.     

Quantification of 5-HT1A and 5-HT2A receptor Binding in Depressed Suicide Attempters and Non-Attempters

Objective: To determine serotonin system abnormalities related to major depression or previous suicidal behavior.

Methods: [¹¹C]WAY100635, [¹⁸F]altanserin and positron emission tomography were used to compare 5-HT_1A and 5-HT_2A binding in MDD patients divided into eight past suicide attempters (>4yrs prior to scanning) and eight lifetime non-attempters, and both groups were compared to eight healthy volunteers.

Results: The two receptor types differed in binding pattern across brain regions from each other, but there were no differences in binding between healthy volunteers and the two depressed groups or between depressed suicide attempters and non-attempters. No effects of depression severity or lifetime aggression were observed for either receptor.

Conclusion: Limitations of this study include small sample size and absence of high lethality suicide attempts in the depressed attempter group. No trait-like binding correlations with past suicide attempt or current depression were observed. Given the heterogeneity of nonfatal suicidal behavior, a larger sample study emphasizing higher lethality suicide attempts may find the serotonin biological phenotype seen in suicide decedents.     

Effect of a patellar realignment brace on patellofemoral relationships: Evaluation with kinematic MR imaging

The effect of a newly developed patellar realignment brace was evaluated in 21 patellofemoral joints (19 patients) with patellar subluxation (13 joints with lateral subluxation and eight with medial subluxation) by using active-movement, loaded kinematic magnetic resonance (MR) imaging. Sixteen patellofemoral joints (76%) demonstrated a qualitative correction of or improvement in patellar subluxation (ie, centralization of the patella or a decrease in the displacement of the patella) after application of the brace. Four of the five “failures” occurred in patellofemoral joints that had patella alta and/or dysplastic bone anatomy. These results indicate that the patellar realignment brace was able to counteract patellar subluxation in the majority of patellofemoral joints studied, as shown by active-movement, loaded kinematic MR imaging. This brace appears to be useful for conservative treatment of patients with patellofemoral joint pain secondary to patellar malalignment and maltracking.     

Physiological pharmacokinetics and pharmacodynamics of (+/-)-verapamil in female rats

Tissue distribution and pharmacodynamics of verapamil were evaluated during steady state intravenous (i.v.) infusion and after single dose intraperitoneal (i.p.) drug administration to female Sprague-Dawley rats. In one group of rats, verapamil was infused to a steady state concentration at which time animals were killed. Verapamil-induced decreases in mean arterial pressure (MAP) were monitored during infusion and correlated with concomitantly obtained plasma verapamil concentrations. Tissue (lung, liver, renal medulla, renal cortex, cardiac muscle, skeletal muscle, perirenal fat, brain stem, cerebral cortex, and cerebellum) and plasma samples were obtained immediately after animals were killed and verapamil and norverapamil concentrations determined. Another group of rats, after receiving i.p. verapamil, were killed at 1, 3, 5, 19, and 24 h. Elimination from each tissue evaluated was described by a first order process. Elimination half-life of verapamil was similar among plasma and tissues evaluated (1.5 to 2.2 h). The per cent verapamil not bound to plasma proteins was concentration-independent and similar between rats receiving i.p. (mean +/- S.D.) (2.28 +/- 0.72 per cent) and i.v. (2.08 +/- 0.03 per cent) verapamil. MAP and verapamil concentration in plasma (r = 0.75; p less than 0.01) and cardiac muscle (r = -0.82; p less than 0.01) were inversely correlated in a highly significant fashion during both i.v. and i.p. drug administrations. The tissue-to-plasma distribution ratio for verapamil and norverapamil was similar among animals receiving i.p. verapamil at all points of sampling, suggesting distribution equilibrium had been achieved. After steady state i.v. infusion, both verapamil and norverapamil tissue: plasma concentration ratios were greater than after i.p. administration. Higher tissue: plasma verapamil concentration ratios after i.v. administration than after i.p. administration suggest either only a pseudoequilibrium is attained after i.p. administration or that determinants of tissue distribution of racemic verapamil differ with different routes of drug administration. In these studies, MAP provided a reasonable pharmacodynamic marker for verapamil tissue and plasma concentrations.     

An Independent Evaluation of Four Quantitative Emergency Department Crowding Scales

Background Emergency department (ED) overcrowding has become a frequent topic of investigation. Despite a significant body of research, there is no standard definition or measurement of ED crowding. Four quantitative scales for ED crowding have been proposed in the literature: the Real‐time Emergency Analysis of Demand Indicators (READI), the Emergency Department Work Index (EDWIN), the National Emergency Department Overcrowding Study (NEDOCS) scale, and the Emergency Department Crowding Scale (EDCS). These four scales have yet to be independently evaluated and compared. Objectives The goals of this study were to formally compare four existing quantitative ED crowding scales by measuring their ability to detect instances of perceived ED crowding and to determine whether any of these scales provide a generalizable solution for measuring ED crowding. Methods Data were collected at two‐hour intervals over 135 consecutive sampling instances. Physician and nurse agreement was assessed using weighted κ statistics. The crowding scales were compared via correlation statistics and their ability to predict perceived instances of ED crowding. Sensitivity, specificity, and positive predictive values were calculated at site‐specific cut points and at the recommended thresholds. Results All four of the crowding scales were significantly correlated, but their predictive abilities varied widely. NEDOCS had the highest area under the receiver operating characteristic curve (AROC) (0.92), while EDCS had the lowest (0.64). The recommended thresholds for the crowding scales were rarely exceeded; therefore, the scales were adjusted to site‐specific cut points. At a site‐specific cut point of 37.19, NEDOCS had the highest sensitivity (0.81), specificity (0.87), and positive predictive value (0.62). Conclusions At the study site, the suggested thresholds of the published crowding scales did not agree with providers' perceptions of ED crowding. Even after adjusting the scales to site‐specific thresholds, a relatively low prevalence of ED crowding resulted in unacceptably low positive predictive values for each scale. These results indicate that these crowding scales lack scalability and do not perform as designed in EDs where crowding is not the norm. However, two of the crowding scales, EDWIN and NEDOCS, and one of the READI subscales, bed ratio, yielded good predictive power (AROC >0.80) of perceived ED crowding, suggesting that they could be used effectively after a period of site‐specific calibration at EDs where crowding is a frequent occurrence.