Characteristics of volunteers responding to emergencies in the Public Access Defibrillation Trial

OBJECTIVES: To evaluate the characteristics of volunteers responding to emergencies in the North American Public Access Defibrillation (PAD) Trial. METHODS: The PAD Trial was a prospective evaluation of cardiac arrest survival in community facilities randomized to cardiopulmonary resuscitation (CPR) or to CPR with automated external defibrillators (AEDs). The PAD volunteers' characteristics were analyzed using Poisson regression clustered on the facility and offset by the number of emergency episodes to which volunteers were exposed. RESULTS: A total of 19,320 volunteers in 1260 facilities were trained to provide emergency care. Of these, 8169 volunteers were participating actively at their facility during a time when one or more emergency episodes occurred. There were 1971 emergency episodes responded to by 1245 volunteers. The treatment arm (CPR-only versus CPR+AED) was not associated with the likelihood of volunteer participation in an episode. Likewise, the volunteers' age or sex did not affect response. Volunteers more likely to respond were supervisory/management or security personnel, non-minority participants, volunteers with previous CPR training, volunteers with previous experience in emergency care and those who passed the PAD CPR skills follow-up test. Volunteers who had a formal education beyond a high school level were less likely to respond. CONCLUSIONS: Volunteers with previous emergency training and positions of responsibility in their facility had a greater likelihood of participation in medical emergencies in the PAD Trial.     

Adrenocortical function during septic shock

Objective To investigate, in patients with severe septic shock, the adrenocortical function assessed by daily plasma cortisol determinations during the first 72 h and by the short synthetic ACTH stimulation test performed within 24 h of the onset of shock. Design Prospective clinical investigation. Setting Medical intensive care unit in a university teaching hospital. Patients 40 consecutive patients with documented septic shock requiring at least hemodynamic resuscitation and respiratory support. Interventions There were no intervention. Measurements and results Basal cortisol concentrations were increased with a mean value of 36.8 μg/dl (range 7.9–113). Of the overall cortisol determinations 92% were above 15 μg/dl. No statistically significant differences in basal cortisol concentrations were found when survival, type of infection, and positive blood cultures were considered. Patients with hepatic disease had significantly higher cortisol (50.1(±6.2) μ/dl versus 35.9(±3.3) μg/dl,p=0.035) levels compared to other patients. No correlations were found between basal plasma cortisol concentrations and factors such as SAPS, OSF, hemodynamic measurements, duration of shock, and amount of vasopressor and/or inotropic agents. Cortisol concentrations had significant but weak correlation with ACTH levels in survivors (r=0.4;p=0.03;n=28) but not in non-survivors (r=0.03;p=0.85;n=52). Cortisol levels in non-survivors increased significantly from enrollment time to the 72nd hour of the survey (day 1: 38.9(±3.8) μg/dl versus day 3: 66.7(±17.1) μg/dl;p=0.046) and were significantly higher than those recorded in survivors. Responses to the short ACTH stimulation test were not significantly different between survivors and non-survivors. According to the different criteria used to interpret the response to the ACTH stimulation test, incidence of adrenocortical insufficiency was highly variable ranging from 6.25–75% in patients with septic shock. Only one patient had absolute adrenocortical insufficiency (basal cortisol level below 10 μg/dl; response to the ACTH stimulation test below 18 μg/dl. Conclusion Our data suggest that in a selected population of patients with severe septic shock single plasma cortisol determination has no predictive value. The short ACTH stimulation test performed within the first 24 h of onset shock can neither predict outcome nor estimate impairment in adrenocortical function in patients with high basal cortisol level. Adrenal insufficiency is rare in septic shock and should be suspected when cortisol level is below 15 μg/dl and then confirmed by a peak cortisol level lower than 18 μg/dl during the short ACTH stimulation test.     

Inhibitory Potential of Antifungal Drugs on ATP-Binding Cassette Transporters P-Glycoprotein,MRP1 to MRP5, BCRP,and BSEP

Inhibition of ABC transporters is a common mechanism underlying drug-drug interactions (DDIs). We determined the inhibitory potential of antifungal drugs currently used for invasive fungal infections on ABC transporters P-glycoprotein (P-gp), MRP1 to MRP5, BCRP, and BSEP in vitro. Membrane vesicles isolated from transporter-overexpressing HEK 293 cells were used to investigate the inhibitory potential of antifungal drugs (250 μM) on transport of model substrates. Concentration-inhibition curves were determined if transport inhibition was >60%. Fifty percent inhibitory concentrations (IC₅₀s) for P-gp and BCRP were both 2 μM for itraconazole, 5 and 12 μM for hydroxyitraconazole, 3 and 6 μM for posaconazole, and 3 and 11 μM for isavuconazole, respectively. BSEP was strongly inhibited by itraconazole and hydroxyitraconazole (3 and 17 μM, respectively). Fluconazole and voriconazole did not inhibit any transport for >60%. Micafungin uniquely inhibited all transporters, with strong inhibition of MRP4 (4 μM). Anidulafungin and caspofungin showed strong inhibition of BCRP (7 and 6 μM, respectively). Amphotericin B only weakly inhibited BCRP-mediated transport (127 μM). Despite their wide range of DDIs, azole antifungals exhibit selective inhibition on efflux transporters. Although echinocandins display low potential for clinically relevant DDIs, they demonstrate potent in vitro inhibitory activity. This suggests that inhibition of ABC transporters plays a crucial role in the inexplicable (non-cytochrome P450-mediated) DDIs with antifungal drugs.     

Flow-cytometric immunophenotyping of normal and malignant lymphocytes.

During the past two decades, flow-cytometric immunophenotyping of lymphocytes has evolved from a research technique into a routine laboratory diagnostic test. Extensive studies in healthy individuals resulted in detailed age-related reference values for different lymphocyte subpopulations in peripheral blood. This is an important tool for the diagnosis of hematological and immunological disorders. Similar, albeit less detailed, information is now available for other lymphoid organs, e.g., normal bone marrow, lymph nodes, tonsils, thymus and spleen. Flow-cytometric immunophenotyping forms the basis of modern classification of acute and chronic leukemias and is increasingly applied for initial diagnostic work-up of non-Hodgkin's lymphomas. Finally, with multiparameter flow cytometry, it is now possible to identify routinely and reliably low numbers of leukemia and lymphoma cells (minimal residual disease).     

羟乙基淀粉溶液在复苏肠缺血再灌注休克中的作用

目的　比较不同剂量羟乙基淀粉溶液 ( HES)对兔肠缺血再灌注损伤所致休克的复苏作用。方法　 32只新西兰白兔随机分为 4组 :模型对照、乳酸林格液复苏组 ( L RS,2 0 m l· kg- 1 · h- 1 ) ,小剂量 HES复苏组 ( HES2 ml· kg- 1· h- 1 L RS18m l· kg- 1· h- 1 ) ,大剂量 HES复苏组 ( HES2 0 ml· kg- 1· h- 1 )。采用肠系膜上动脉夹闭 6 0 m in后松夹行再灌注制备肠缺血再灌注休克模型 ,松夹再灌注时同步进行液体复苏。观测各时间点的血流动力学参数 (平均动脉压、心率、心排血量、肠系膜上动脉血流 ) ,并通过测定肠黏膜CO2 分压和动脉血 CO2 分压的差值 (动脉二氧化碳间隙 )、肠黏膜 p H值、动脉血乳酸浓度和氧输送等指标间接评估组织氧合情况。实验结束后累计动物死亡数。结果　 HES能明显提高肠缺血再灌注休克时的血流动力学参数 ,与对照组和 L RS组比较差异均有显著性 ( P均 <0 .0 5 ) ;小剂量 HES比大剂量 HES改善血流动力学参数的作用更平稳 ( P均 <0 .0 5 ) ,且较其他 3组能明显降低血乳酸浓度和动脉二氧化碳间隙 ,减轻 p Hi的降低 ( P均 <0 .0 5 ) ;而大剂量 HES对上述参数的影响不明显 ,并可见动物口鼻出血及死亡 ;小剂量或大剂量HES与其他两组比较均能使氧输送回升 ( P均 <0 .0 5 )。结     

Differential effects of a selective inhibitor of soluble guanylyl cyclase on global and regional hemodynamics during canine endotoxic shock

Activation of soluble guanylyl cyclase (sGC) might occur early during septic shock and play a role in the regulation of vascular tone and the redistribution of blood flow. The aim of this study was to assess the effects of sGC inhibition with oxadiazoloquinoxalinone (ODQ) on global and regional hemodynamic parameters in a clinically relevant model of septic shock. Fifteen anesthetized adult mongrel dogs were equipped with femoral and pulmonary artery catheters and ultrasonic flow probes around the mesenteric, femoral and renal arteries. The animals were randomized to receive Escherichia coli endotoxin (2 mg/kg, i.v.) alone, endotoxin followed by ODQ (1 mg/kg i.v.), or ODQ alone. Endotoxin administration was followed by decreases in mean arterial pressure, cardiac index, mesenteric, renal and femoral blood flows (MBF, RBF and FBF), and increases in systemic and pulmonary vascular resistances. Fluid resuscitation restored cardiac index, systemic vascular resistance, pulmonary vascular resistance, MBF, RBF and FBF to pre-endotoxin levels. In the presence of endotoxin, ODQ administration increased MBF and prevented the restoration of FBF. Hence, selective inhibition of sGC may increase splanchnic blood flow in septic shock.     

The Effect of Ergotamine on Prostaglandin Formation in Guinea Pig''s Ear Slices

SYNOPSIS
We have studied the effect of ergotamine tartrate (10⁻⁷ and 10⁻⁵ M) on prostaglandin (PG) formation in guinea pig's ear slices because of the suggested role of PGs in the pathophysiology of the migraine attack. The ear slices were incubated with arachidonic acid (AA) and the amount of different PGs (6-keto-F_1a, F_2a, E₂, D₂ and A₂) in the incubation medium was determined. The results indicate that ergotamine is an inhibitor of PG synthesis and that it probably affects either the phospholipase A₂ or the cyclo-oxygenase activity.