Citations

BackgroundGroup O red blood cell (RBC) units are used for emergency transfusions and are often uncrossmatched when transfused. We sought to determine the risk of alloimmunization and identify acute adverse outcomes of this practice.Study Design and MethodsThe transfusion medicine database was searched for emergency‐release transfusion (ERT) episodes from January 2006 through December 2010. The data collected included age and sex of the recipient, blood bank history, survival after the ERT episode, antibody screen results, antibody identifications, and compatibility of released units.ResultsA total of 1444 ERT episodes took place involving 1407 patients. A total of 4144 RBC units were released. Of the 129 positive antibody screens, 34 had no antibody on further work‐up, 14 had autoantibodies, 48 had a single antibody specificity, and 25 had multiple antibody specificities. Seven patients developed an antibody that could be attributed to the ERT episode, and 15 patients developed an antibody after ERT and additional RBC transfusions. There were 32 reported suspected transfusion reactions. No acute hemolytic transfusion reactions were reported. Seven patients were given a total of 10 incompatible RBC units. Of these patients, one developed a delayed serologic transfusion reaction. The rate of alloimmunization attributable to ERT was 3%. Overall, the rate of incompatible transfusion was less than 0.3% and the rate of a delayed hemolytic transfusion reaction was approximately 0.02%.ConclusionThere is minimal risk associated with the release of emergency uncrossmatched blood in the setting of an acutely bleeding patient. [Correction statement added after online publication 15‐Oct‐2012: the number of patients with autoantibodies, single antibody specificity and multiple antibody specificity has been update.]

Clinically observed differences in airway reactivity and asthma exacerbations in women at different life stages suggest a role for sex steroids in modulating airway function although their targets and mechanisms of action are still being explored. We have previously shown that clinically relevant concentrations of exogenous estrogen acutely decrease intracellular calcium ([Ca2+]i) in human airway smooth muscle (ASM), thereby facilitating bronchodilation. In this study, we hypothesized that estrogens modulate cyclic nucleotide regulation, resulting in decreased [Ca2+]iin human ASM. In Fura-2-loaded human ASM cells, 1 nM 17β-estradiol (E2) potentiated the inhibitory effect of the β-adrenoceptor (β-AR) agonist isoproterenol (ISO; 100 nM) on histamine-mediated Ca2+entry. Inhibition of protein kinase A (PKA) activity (KT5720; 100 nM) attenuated E2effects on [Ca2+]i. Acute treatment with E2increased cAMP levels in ASM cells comparable to that of ISO (100 pM). In acetylcholine-contracted airways from female guinea pigs or female humans, E2potentiated ISO-induced relaxation. These novel data suggest that, in human ASM, physiologically relevant concentrations of estrogens act via estrogen receptors (ERs) and the cAMP pathway to nongenomically reduce [Ca2+]i, thus promoting bronchodilation. Activation of ERs may be a novel adjunct therapeutic avenue in reactive airway diseases in combination with established cAMP-activating therapies such as β2-agonists.

Background and Purpose— ResolutionMD mobile application runs on a Smartphone and affords vascular neurologists access to radiological images of patients with stroke from remote sites in the context of a telemedicine evaluation. Although reliability studies using this technology have been conducted in a controlled environment, this study is the first to incorporate it into a real-world hub and spoke telestroke network. The study objective was to assess the level of agreement of brain CT scan interpretation in a telestroke network between hub vascular neurologists using ResolutionMD, spoke radiologists using a Picture Archiving and Communications System, and independent adjudicators. Methods— Fifty-three patients with stroke at the spoke hospital consented to receive a telemedicine consultation and participate in a registry. Each CT was evaluated by a hub vascular neurologist, a spoke radiologist, and by blinded telestroke adjudicators, and agreement over clinically important radiological features was calculated. Results— Agreement ( κ and 95% CI) between hub vascular neurologists using ResolutionMD and (1) the spoke radiologist; and (2) independent adjudicators, respectively, were: identification of intracranial hemorrhage 1.0 (0.92–1.0), 1.0 (0.93–1.0), neoplasm 1.0 (0.92–1.0), 1.0 (0.93–1.0), any radiological contraindication to thrombolysis 1.0 (0.92–1.0), 0.85 (0.65–1.0), early ischemic changes 0.62 (0.28–0.96), 0.58 (0.30–0.86), and hyperdense artery sign 0.40 (0.01–0.80), 0.44 (0.06–0.81). Conclusions— CT head interpretations of telestroke network patients by vascular neurologists using ResolutionMD on Smartphones were in excellent agreement with interpretations by spoke radiologists using a Picture Archiving and Communications System and those of independent telestroke adjudicators using a desktop viewer. Clinical Trial Registration Information— www.clinicaltrials.gov unique identifier NCT00829361.

OBJECTIVE To investigate the pharmacokinetics (PK), pharmacodynamics, and safety of single-dose RM-131 in type 2 diabetic patients with gastrointestinal cardinal symptoms (GCSI) and previously documented delayed gastric emptying (DGE). RESEARCH DESIGN AND METHODS In a randomized crossover study, 10 female patients received RM-131 (100 μg s.c.) or placebo and underwent scintigraphic gastric emptying (GE) and colonic filling at 6 h (CF6) of a solid-liquid meal administered 30 min postdosing. Adverse events, plasma glucose, and hormonal levels were assessed. GCSI daily diary (GCSI-DD) was completed during treatments. PK was assessed in this cohort and healthy volunteers (HVs). RESULTS At screening, HbA1c was 7.2 ± 0.4% (SEM) and total GCSI-DD score was 1.32 ± 0.21. RM-131 accelerated GE t1/2 of solids (P = 0.011); mean difference (Δ) in solid GE t1/2 was 68.3 min (95% CI 20–117) or 66.1%. There were numerical differences in GE lag time, CF6 solids, and GE t1/2 liquids (all P < 0.14). With a significant (P < 0.014) order effect, further analysis of the first treatment period (n = 5 per group) confirmed significant RM-131 effects on GE t1/2 (solids, P = 0.016; liquids, P = 0.024; CF6, P = 0.013). PK was similar in DGE patients and HVs. There were increases in 120-min blood glucose (P = 0.07) as well as 30–90-min area under the curve (AUC) levels of growth hormone, cortisol, and prolactin (all P < 0.02) with single-dose RM-131. Only light-headedness was reported more on RM-131. CONCLUSIONS RM-131 greatly accelerates the GE of solids in patients with type 2 diabetes and documented DGE. PK is similar in diabetic patients and HVs.

AbstractSurprisingly, the role(s) of eosinophils in health and disease is often summarized by clinicians and basic research scientists as a pervasive consensus opinion first learned in medical/graduate school. Eosinophils are rare white blood cells whose activities are primarily destructive and are only relevant in parasitic infections and asthma. However, is this consensus correct? This review argues that the wealth of available studies investigating the role(s) of eosinophils in both health and disease demonstrates that the activities of these granulocytes are far more expansive and complex than previously appreciated. In turn, this greater understanding has led to the realization that eosinophils have significant contributory roles in a wide range of diseases. Furthermore, published studies even implicate eosinophil-mediated activities in otherwise healthy persons. We suggest that the collective reports in the literature showing a role for eosinophils in an ever-increasing number of novel settings highlight the true complexity and importance of this granulocyte. Indeed, discussions of eosinophils are no longer simple and more often than not now begin with the question/statement “Did you know …?”

Prostate cancer is the second leading cause of cancer death among United States men. However, disease aggressiveness is varied, with low-grade disease often being indolent and high-grade cancer accounting for the greatest density of deaths. Outcomes are also disparate among men with high-grade prostate cancer, with upwards of 65% having disease recurrence even after primary treatment. Identification of men at risk for recurrence and elucidation of the molecular processes that drive their disease is paramount, as these men are the most likely to benefit from multimodal therapy. We previously showed that androgen-induced expression profiles in prostate development are reactivated in aggressive prostate cancers. Herein, we report the down-regulation of one such gene, Sparcl1 , a secreted protein, acidic and rich in cysteine (SPARC) family matricellular protein, during invasive phases of prostate development and regeneration. We further demonstrate a parallel process in prostate cancer, with decreased expression of SPARCL1 in high-grade/metastatic prostate cancer. Mechanistically, we demonstrate that SPARCL1 loss increases the migratory and invasive properties of prostate cancer cells through Ras homolog gene family, member C (RHOC), a known mediator of metastatic progression. By using models incorporating clinicopathologic parameters to predict prostate cancer recurrence after treatment, we show that SPARCL1 loss is a significant, independent prognostic marker of disease progression. Thus, SPARCL1 is a potent regulator of cell migration/invasion and its loss is independently associated with prostate cancer recurrence.