应用99mTc-DTPA肾动态显像和双血浆法评估肾小球滤过率的一致性研究

目的:以双血浆法(dual GFR,dGFR)为标准,评价应用肾动态显像Gates法评估肾小球滤过率(GFR)的准确性和可靠性。方法:2009年6月至2010年6月可引起不同程度肾功能损害的各种常见病患者202例,男123例,女79例,平均年龄(49.5±3.9)岁,共398个肾。依据dGFR法并按Gates法分肾比值计算分肾GFR,将各肾分5级:normal(≥40)、4(30～39.9)、3(20～29.9)、2(10～19.9)、1(<10)[单位为mL/min·(1.73m2)]。分别采用Pearson相关分析和Bland-Altman检验比较dGFR法与Gates法的相关性和一致性。结果:normal级79个肾,4级74个肾,3级84个肾,2级87个肾,1级74个肾。(1)Gates法和dGFR法总体上有显著相关性(r=0.722,P=0.000),回归方程为:Gates=16.708+0.505dGFR;3、4、normal级呈显著弱相关性(分别为r=0.341,P=0.002;r=0.368,P=0.002与r=0.319,P=0.004),回归方程分别为Gates=-9.7+1.899 dGFR、Gates=31.671+0.060dGFR和Gates=17.225+0.879dGFR;1、2级无显著相关性(分别为r=0.038,P=0.747与r=0.198,P=0.077)。(2)Bland-Altman检验结果提示,Gates法和dGFR法的一致性各级患者均欠佳。结论:肾动态显像Gates法测量GFR的准确性尚可,但对其结果应按dGFR法回归计算以获得更准确的GFR,且对于1、2级患者仍应行dGFR法。     

A noninvasive method of estimating mean pulmonary artery pressure in the pneumatic total artificial heart

Accurate hemodynamic monitoring is essential for the clinical management of the recipient of a total artificial heart (TAH). The high incidence of pulmonary congestive disorders in this population complicates this already formidable task. Lack of diagnostic pulmonary artery pressure (PAP) information is recognized as a fundamental source of these problems. Because conventional methods of obtaining hemodynamic information are difficult to implement in TAH recipients, improvement of TAH case management depends on the development of innovative monitoring strategies. Noninvasive monitoring techniques have been developed for three (right atrial pressure, left atrial pressure, and aortic pressure) of the four auxiliary circulatory pressures used to quantify hemodynamic performance. Development of the fourth, for PAP, was the subject of this work. We developed a noninvasive, in vitro method of estimating mean PAP in the Jarvik-7 TAH (Symbion, Inc, Salt Lake City, UT) recipient. This information was obtained by analyzing the relationship between the pneumatic right drive pressure (RDP) and PAP waveforms produced by a Jarvik-7 (70 ml) connected to a Donovan mock circulation and driven by a Utahdrive System IIIe Controller (Symbion, Inc, Salt Lake City, UT). Total artificial heart driver parameters (i.e., heart rate, percent systole, and vacuum) were manipulated to produce a range of ventricular filling volumes (FV), from 40 to 60 ml, for three distinct states of the pulmonary vasculature: hypotensive, normal, and hypertensive. A unique multiple-linear regression equation was derived for each FV from the RDP-PAP relationship exhibited under these conditions. Comparison of computed estimates of PAP with actual measurements showed overall average correlations of greater than 0.92, with a standard error of the estimate of less than 1.9 mm Hg. The mean difference between actual and computed PAP measurements was –0.03 ±2.0 Hg. Estimations were accurate within 8.5% of true PAP values. Additional experimentation revealed that while the RDP-PAP relationships are dependent on FV, they are independent of the manner in which FV was obtained. Estimates proved useful over the clinical operating range of the pneumatic heart driver, as well as over the normal physiologic range of PAP in the human. This method is readily applicable to a computer-based monitoring implementation, although its effectiveness needs to be demonstrated in vivo.     

Uptake and efflux kinetics,and intracellular activity of voriconazole against Aspergillus fumigatus in human pulmonary epithelial cells: a new application for the prophylaxis and early treatment of invasive pulmonary aspergillosis

Invasive pulmonary aspergillosis (IPA), most caused by Aspergillus fumigatus, is a serious life‐threatening infection in immunocompromised patients. Voriconazole is used to prevent and treat IPA. However, little is known about the pharmacological characteristics of voriconazole in pulmonary epithelial cells, which are the target site for the prophylaxis and early treatment of IPA. The aim of the study was to evaluate the kinetics and activity of voriconazole against A. fumigatus in A549 cells. High‐performance liquid chromatography/tandem mass spectrometry and time‐kill method were used to study the cellular pharmacokinetic and pharmacodynamics of voriconazole. Voriconazole exerted a concentration‐dependent toxic effect on A549 cells and could penetrate into cells, reaching plateau concentrations of 1.14 ± 0.64, 3.72 ± 1.38 and 6.36 ± 0.95 ng/mg protein after A549 cells were exposed to voriconazole at extracellular concentrations of 2, 8 and 16 mg/L for 2 h, respectively. The efflux of voriconazole was rapid, with a half‐life of 10.2 min. Voriconazole can decrease the A. fumigatus conidia invade cells, and the number of viable A. fumigatus conidia in cells can be decreased 2.1‐ to 20.6‐fold when A549 cells were cultured in medium containing voriconazole. After 24‐h incubation, 75.6% and 80.5% of intracellular A. fumigatus were killed when extracellular voriconazole concentration was 8 and 16 mg/L, respectively. This study illustrated a new application for the prophylaxis and early treatment of IPA from the cellular pharmacokinetics and pharmacodynamics and emphasized the importance of monitoring concentrations of voriconazole in epithelial lining fluid in immunocompromised patients receiving voriconazole therapy.     

A single plasma sample method for estimation of the glomerular filtration rate in infants and children using iohexol, II: Establishment of the optimal plasma sampling time and a comparison with the 99Tcm-DTPA method

The glomerular filtration rate (GFR) can be determined from the plasma disappearance rate of the non-ionic contrast medium iohexol. A preceding study established the empirical formulae enabling the development of a single plasma sample method for estimation of GFR in infants and children. In the present study the validity of these empirical formulae was confirmed in examinations in 143 patients. The results of the single plasma sample method were similar to those of a standard 99Tcm-DTPA method, and also with those of a two plasma sample iohexol method. Evaluation of the results obtained with plasma sampling 1 h, 2 h, 3 h and 4 h after the injection of the contrast medium showed that the optimal sampling time was about 3 h after the injection.