The postoperative blood-sparing efficacy of oral versus intravenous tranexamic acid after total knee replacement

To assess the blood-sparing efficacy of tranexamic acid (TA) administered orally or via a variable IV infusion, 80 healthy patients undergoing elective total knee replacement were studied according to a prospective, controlled, randomized, single-blinded study design. Patients were allocated to one of four treatment groups. In group TA-long, 30 min before deflation of the limb tourniquet, an IV bolus dose of TA 15 mg/kg was administered over 30 min. Thereafter, a constant IV infusion of 10 mg . kg(-1) . h(-1) was administered until 12 h after final deflation of the limb tourniquet. In group TA-short, a similar regimen was followed; however, the constant IV infusion was discontinued 2 h after final deflation of the limb tourniquet (time of discharge from the postanesthesia care unit). Thereafter, oral TA 1 g was administered after 6 and 12 h. In group TA-oral, 60 min before surgery an oral dose of TA 1 g was administered. After surgery, a similar dose of TA was administered every 6 h for the next 18 h. In the control group, TA was not administered. At patient discharge, postoperative allogeneic blood administration was significantly more in group Control when compared with each of the three TA treatment groups. Because oral drug administration is simple and does not require specific infusion equipment, the authors suggest that oral TA is a superior blood-sparing strategy compared with IV drug administration.     

Lower limb wrapping prevents hypotension, but not hypothermia or shivering, after the introduction of epidural anesthesia for cesarean delivery

The decrease of arterial blood pressure and body temperature after epidural or spinal anesthesia is thought to be the result of sympathetic block, which could cause pooling and redistribution of blood into the lower extremities. Studies have demonstrated that leg wrapping with elastic bandages may reduce the incidence of hypotension after spinal anesthesia. We tried to extend these previous observations to epidural anesthesia by testing the hypothesis that leg wrapping with elastic bandages should decrease the incidence of hypotension in patients receiving epidural anesthesia. Moreover, we evaluated the effect of this maneuver as regards hypothermia and shivering. Sixty parturients were randomly allocated to receive either leg wrapping with tight elastic bandages (leg-wrapped group) or not (control group) before anesthesia. Sublingual temperature was observed at five periods: baseline, immediately after epidural anesthesia, abdominal skin disinfection, skin incision, and delivery. Hypotension and shivering during the observation periods were also recorded. The incidence of hypotension was significantly less frequent (P = 0.03) in the leg-wrapped group (23%) compared with the control group (50%). Shivering incidences were similar in both groups (70% versus 70%). Sublingual temperature decreased significantly (P < 0.001) throughout the procedure in each group. However, no differences were found between the two groups at each designated observation, even if compared by the magnitude of temperature decrease. We conclude that although leg wrapping with elastic bandages prevents maternal hypotension after epidural anesthesia, it does not reduce the incidence or magnitude of hypothermia or prevent shivering.     

Myocardial protection using fructose-1,6-diphosphate during coronary artery bypass graft surgery: a randomized, placebo-controlled clinical trial

In vitro and in vivo studies suggest that fructose-1,6-diphosphate (FDP), an intermediary glycolytic pathway metabolite, ameliorates ischemic tissue injury through increased high-energy phosphate levels and may therefore have cardioprotective properties in patients undergoing coronary artery bypass graft (CABG) surgery. We designed a randomized, placebo-controlled, double-blinded, sequential-cohort, dose-ranging safety study to test 5 FDP dosage regimens in patients (n = 120; 60 FDP, 60 control) undergoing CABG surgery. Of these dosage regimens, 3 produced no benefit, 1 produced improved cardiac function, and 1 required adjustment as a result of metabolic acidosis. This suggests that we achieved the intended effect of a dose-ranging study. The expected response was observed in patients treated with 250 mg/kg FDP IV before surgery and 2.5 mM FDP as a cardioplegic additive (n = 15). These patients had lower serum creatine kinase-MB levels 2, 4, and 6 h after reperfusion (P < 0.05), fewer perioperative myocardial infarctions (P < 0.05), and improved postoperative cardiac function, as evidenced by higher left ventricular stroke work index (LVSWI) 6, 12, and 16 h (P < 0.01) and cardiac index (CI) at 12 and 16 h (P < 0.05) after reperfusion. Overall efficacy of FDP was tested across all regimens that included IV FDP (n = 88; 44 FDP, 44 control) using 2 (FDP versus placebo) x 3 (dose size) factorial analyses. Area-under-curve (AUC) analysis demonstrated a significant increase in CI (AUC-16h, P = 0.013) and LVSWI (AUC-16h, P = 0.003) and reduction in CK-MB levels (AUC-16h, P < 0.05) in FDP-treated patients. The internal consistency of this dataset suggests that FDP may provide myocardial protection in CABG surgery and supports previous laboratory and clinical studies of FDP in ischemic heart disease. IMPLICATIONS: Fructose-1,6-diphosphate (FDP) may increase high-energy phosphate levels under anaerobic conditions and therefore ameliorate ischemic injury. A dose-ranging safety study for FDP was conducted in patients undergoing coronary artery surgery. Preischemic provision of FDP significantly improved cardiac function and reduced perioperative ischemic injury. These myocardial protective effects may improve patient outcome after cardiac surgery.     

High frequency oscillatory ventilation in burn patients with the acute respiratory distress syndrome

BACKGROUND: High frequency oscillatory ventilation (HFOV) improves gas exchange while providing lung protective effects during the ventilation of patients with the acute respiratory distress syndrome (ARDS). The purpose of this study was to review our experience with HFOV in adult burn patients with oxygenation failure secondary to ARDS. METHODS: Retrospective cohort review of all burn patients treated with HFOV at a regional adult burn center. RESULTS: All values are reported as the mean +/- standard deviation (S.D.). HFOV was used on 28 occasions in 25 patients (age 44 +/- 16 years, %TBSA burns 40 +/- 15, and a 28% incidence of inhalation injury) who had severe oxygenation failure from ARDS (PaO2/FiO2 ratio 98 +/- 26, and oxygenation index (OI) (FiO2 x 100 x mean airway pressure/PaO2) 27 +/- 10) following 4.8 +/- 4.4 days of conventional mechanical ventilation (CMV). After switching from CMV to HFOV, there were significant improvements in the PaO(2)/FiO2 ratio within 1h and in the oxygenation index within 24 h. The duration of HFOV was 6.1 +/- 5.8 days. HFOV was continued during 26 surgeries for 14 patients where a mean of 18 +/- 9% TBSA burns were excised and closed. The only complications related to HFOV were three episodes of severe hypercapnia. In-hospital mortality was 32%. CONCLUSIONS: HFOV was safe, and was highly effective in correcting oxygenation failure associated with ARDS in burn patients, and can be successfully used as an intra-operative ventilation modality for burn patients.     

Continuous pulse oximeter monitoring for inapparent hypoxemia after long bone fractures

BACKGROUND: Continuous pulse oximeter monitoring (CPOM) and daily intermittent arterial blood gas (ABG) were used to define the incidence, pattern, and severity of inapparent hypoxemia after long bone fractures. METHOD: Twenty long bone fracture patients and 19 normal control patients were studied. CPOM, daily ABG, hypoxic symptoms, and features of fat embolism syndrome were monitored for 72 hours after fractures and after surgical interventions. RESULTS: CPOM trend curves showed that all fracture patients except one had recurrent desaturations below 90% Sao2 of varying duration and depth. The lowest Sao2 was down to 60% and the longest episode lasted for 1.47 hours. ABG analysis could not show the recurrent phenomena and never detected the corresponding desaturation episodes. Long bone fracture patients had more desaturation episodes, longer total desaturation duration, and larger total area under desaturation curves in both the postfracture and postoperative periods (p < 0.05). The mean Sao2 was significantly lower in the postfracture period. Although most patients remained asymptomatic and recovered spontaneously, two required transient oxygen therapy and one progressed to fat embolism syndrome. CONCLUSION: Inapparent hypoxia with profound desaturation is common after long bone fractures. CPOM of all patients admitted with long bone fractures is recommended for early detection. In patients who develop inapparent hypoxia, additional pulmonary insult should be avoided or undertaken with care and well timed.     

Group I metabotropic receptor antagonism blocks depletion of calcium stores and reduces potentiated capacitative calcium entry in strain-injured neurons and astrocytes

Antagonism of the group I metabotropic receptor subtype 1 (mGluR1) with (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) has been shown to reduce deficits after in vivo or in vitro traumatic brain injury. We have previously demonstrated that AIDA prevents elevation of astrocyte IP3 subsequent to injury-induced activation of mGluRs and phospholipase C. Since IP3 can cause release of intracellular Ca2+ stores we tested the hypothesis that pre- or post-injury treatment with AIDA can affect (1) the depletion of Ca2+ stores which occurs soon after strain injury of cultured neurons and astrocytes and (2) the delayed potentiation of capacitative calcium entry in strain-injured neurons. Astrocyte or neuronal plus glial cultures were grown on Silastic membranes that were subjected to a 50-msec pulse of compressed gas, which caused membrane displacement and biaxial strain (stretch) injury of the adhering cells. Cells were treated 10 min before or immediately after injury with 100 microM AIDA and the intracellular free Ca2+ ([Ca2+]i) response to thapsigargin, which inhibits the ability of the stores to sequester Ca2+, was measured at 15 min or 3 h after injury. AIDA pre- or post-injury treatment prevented the depletion of intracellular calcium stores at 15 min post-injury in astrocytes and neurons and reduced the potentiated neuronal capacitative calcium influx 3 h after injury. Since Ca2+ and Ca2+ stores influence many factors, including neuronal excitability, plasticity, protein synthesis, and neuronal-glial interactions, prevention of Ca2+ store depletion and subsequent exaggerated capacitative calcium entry may be an important subcellular mechanism by which antagonism of mGluR1 receptors exert an injury-reducing effect. More globally, the results further emphasize the importance of altered signaling and calcium regulatory mechanisms in the immediate and delayed sequelae of traumatic brain injury.     

Influence of annual mammography from age 40 on breast cancer pathology

The objective of this study was to determine the influence of annual mammography on pathology features of breast cancers in an invited population. We conducted a randomized trial of 53,890 invited and 106,971 control United Kingdom women who were recruited only from those aged 40 years, with central review of cancer histology. We compare the invasive cancer distribution for the categories of size, histological type, grade, and node status in subgroups of the invited population with that of controls. Among 1287 cancers identified in the total population through the end of December 1999, there are major differences among prevalence, incidence, interval, and lapsed-attender and nonattender subgroups for the distribution of cancer numbers in categories of chosen qualitative histological features. These reflect the biases known to affect a population exposed to screening. Comparing cancers from the unbiased group of the invited population with controls shows significant differences in distributions for size, grade, and node status but not histological type. Multivariate logistic regression shows significant reduction (odds ratio, 0.73; P = 0.043) in node-positive status for the unbiased group. We conclude that annual mammography from age 40 years significantly reduces size and positive-node status of invasive cancers in the invited population. The potential for phenotypic drift of grade emphasizes the relevance of screen detection of all grades at sizes smaller than 10 mm.     

Smallpox models as policy tools

Mathematical models can help prepare for and respond to bioterrorism attacks, provided that their strengths and weaknesses are clearly understood. A series of initiatives within the Department of Health and Human Services brought modelers together with biologists and epidemiologists who specialize in smallpox and experts in bioterrorism response and health policy and has led to the parallel development of models with different technical approaches but standardized scenarios, parameter ranges, and outcome measures. Cross-disciplinary interactions throughout the process supported the development of models focused on systematically comparing alternate intervention strategies, determining the most important issues in decision-making, and identifying gaps in current knowledge.     

靶向表皮生长因子受体的小分子干扰RNA抑制TJ905人脑胶质瘤细胞增殖和侵袭的实验研究

目的　比较靶向表皮生长因子受体 (EGFR)的小分子干扰RNA与反义RNA构建体对TJ90 5人脑胶质瘤细胞增殖和侵袭的抑制作用。方法　选择人EGFR的二个siRNA靶序列构建靶向EGFR的siRNA表达质粒 ,并以反义EGFRRNA为对照进行脂质体介导的TJ90 5人脑恶性胶质瘤细胞系表达。应用免疫荧光和蛋白印迹检查EGFR的表达水平 ;应用TUNEL法分析细胞凋亡 ,流式细胞术分析细胞周期变化 ,MTT法分析细胞增殖 ;蛋白印迹检测基质金属蛋白酶 9的表达 ,明胶酶谱分析MMP9酶活性 ,Transwell法分析侵袭能力。结果　与TJ90 5细胞和转染空载体的TJ90 5细胞比较 ,转染反义EGFRRNA使EGFR表达下调 82 % ,转染siRNA表达质粒组EGFR表达下调 90 %和 92 %。TJ90 5组和空载转染组几乎没有凋亡细胞 ,反义EGFR转染组与siRNA表达质粒组的凋亡率明显增加 ( χ2 =31 5 4 9,P <0 0 0 1) ;siRNA表达载体转染后S期指数较对照和反义RNA转染组细胞明显减少 ,与TJ90 5组和空载转染组比较 ,转染组细胞自第 1天起存活率均明显下降 (P <0 0 0 1) ,且反义组与siRNA表达载体转染组之间存活率差异有显著意义 (P <0 0 1) ;同时蛋白印迹发现转染siRNA表达载体后MMP 9的表达明显下调 ,明胶酶谱分析发现在反义组与siRNA表达载体转染组MMP 9酶活性明显下降 ,以siRNA