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The safety and pharmacokinetics of L-627, a new injectable carbapenem antibiotic, were evaluated in healthy volunteers. In single-dose studies, 20, 40, 80, 150, 300 and 600 mg of L-627 were administered by i.v. infusions over 1 hour. Plasma concentration-time profiles were well described with a two-compartment open model. The half-life of elimination from plasma was 1.3 +/- 0.8 (mean +/- SD) hour, and the Cmax and AUC paralleled the doses given. The mean urinary recovery of unchanged L-627 within the first 12 hours was 63.1 +/- 2.7% of the dose. In the multiple-dose studies, 300 mg of L-627 (i.v. over 1 hour) was administered every 12 hours, 11 times in total and 600 mg of L-627 was administered every 12 hours, 9 times in total. No discernible accumulation of the drug in plasma was observed. There were no subjective or objective abnormal findings definitely attributable to the drug except that one subject in one of the multiple-dose regimens (300 mg b.i.d.) showed only a slight elevation of transaminase value, although the elevated value promptly recovered after completion of dosing. No abnormality was observed in the other multiple-dose regimen (600 mg b.i.d.). From these results, L-627 was concluded to be safe and well tolerated.  相似文献   
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Intravascular perfluorochemical (PFC) emulsions together with a high oxygen (O2) tension may increase the delivery of dissolved O2 to useful levels. A severely anemic model of cardiopulmonary bypass (CPB) was used to test the hypothesis that a novel PFC emulsion (PFCE; Oxygent [Alliance Pharmaceutical Corp., San Diego, CA] 90% w/v perflubron) used at a high PO2 during bypass delivers sufficient O2 to ameliorate hypoxic myocardial contractile dysfunction. Acutely anemic dogs (N = 42; hematocrit = 15.8 +/- 0.6% [mean +/- SEM] before CPB and 10.9 +/- 0.1% during CPB) were divided into four groups. Group 1 was a control (n = 12). As CPB was initiated, groups 2 (n = 10), 3 (n = 10), and 4 (n = 10) had 1.35 g PFC.kg-1, 2.7 g PFC.kg-1, or 5.4 g PFC.kg-1 added via the venous return cannula. Pre-CPB and post-CPB cardiac function was measured by the first derivative of left ventricular pressure (dP/dtmax). The dP/dtmax on separation from CPB was: group 1, 619 +/- 96; group 2, 738 +/- 56; group 3, 782 +/- 101; and group 4, 828 +/- 100 (p < 0.05 groups 3 and 4 versus group 1). Mortality during the first hour after separation from CPB was higher in group 1 than in PFCE treated dogs; however, this trend did not attain statistical significance (p < 0.065). The PFC dose was higher in survivors than in nonsurvivors (2.6 +/- 0.4 g PFC.kg-1 versus 1.2 +/- 0.5 g PFC.kg-1; p < 0.05). A PFCE used at a high PO2 provides sufficient physically dissolved O2 to relieve myocardial hypoxic injury in a severely anemic model of CPB. Current PFCEs are effective O2 carriers. This finding suggests that they can be used as a temporary erythrocyte substitute to diminish the need for allogeneic transfusions during cardiac operations.  相似文献   
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Characterization of voltammetric signals recorded with microelectrodes in the living brain is fraught with difficulties. In addition to being anatomically complicated, brain tissue presents the analytical electrochemist with a complex chemical environment that includes surfactants (lipids), electrode poisons (proteins), electrocatalysts such as glutathione and ascorbic acid, and a tissue matrix that both restricts mass transport to the electrode surface and reacts physiologically to the presence of the probe. Identification of electrochemical signals recorded in vivo with carbon paste electrodes is discussed in the context of these problems. This examination shows that modification of both the electrode surface by tissue, and of the tissue environment by the electrode have important implications for voltammetric signal analysis in vivo. Despite these problems, valuable data on the relationship between behaviour and chemical changes in the brain can be obtained using in vivo electrochemical techniques.  相似文献   
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BACKGROUND: Transillumination of the soft tissue of the neck using a lighted stylet (lightwand) is an effective and safe intubating technique. A newly designed lightwand (Trachlight) incorporates modifications to improve the brightness of the light source as well as flexibility. The goal of this study was to determine the effectiveness and safety of this device in intubating the trachea of elective surgical patients. METHODS: Healthy surgical patients were studied. Patients with known or potential problems with intubation were excluded. During general anesthesia, the tracheas were intubated randomly using either the Trachlight or the laryngoscope. Failure to intubate was defined as lack of successful intubation after three attempts. The duration of each attempt was recorded as the time from insertion of the device into the oropharynx to the time of its removal. The total time to intubation (TTI), an overall measure of the ease of intubation, was defined as the sum of the durations of all (as many as three) intubation attempts. Complications, such as mucosal bleeding, lacerations, dental injury, and sore throat, were recorded. RESULTS: Nine hundred fifty patients (479 in the Trachlight group and 471 in the laryngoscope group) were studied. There was a 1% failure rate with the Trachlight, and 92% of intubations were successful on the first attempt, compared with a 3% failure rate and an 89% success rate on the first attempt with the laryngoscope (P not significant). All failures were followed by successful intubation using the alternate device. The TTI was significantly less with the Trachlight compared with the laryngoscope (15.7 +/- 10.8 vs. 19.6 +/- 23.7 s). For laryngoscopic intubation, the TTI was longer for patients with limited mandibular protrusion and mentohyoid distance, with a larger circumference of the neck, and with a high classification according to Mallampatti et al. However, there was no relation between the TTI and any of the airway parameters for Trachlight. There were significantly fewer traumatic events in the Trachlight group than in the laryngoscope group (10 vs. 37). More patients complained of sore throat in the laryngoscope group than in the Trachlight group (25.3% vs. 17.1%). CONCLUSIONS: In contrast to laryngoscopy, the ease of intubation using the Trachlight does not appear to be influenced by anatomic variations of the upper airway. Intubation occasionally failed with the Trachlight but in all cases was resolved with direct laryngoscopy. The failures of direct laryngoscopy were resolved with Trachlight. Thus the combined technique was 100% successful in intubating the tracheas of all patients.  相似文献   
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The fatigue life of a welded aluminium T‐joint made from beams with rectangular hollow section (RHS) has been predicted using a crack propagation analysis and compared with experimental results from joints with different residual stress levels. To include the effect of the residual stresses, the stress ratio was calculated at the weld toe and, via Walker's equation, introduced into the analysis. How to obtain the Walker exponent has been discussed in detail. The introduction of a stress ratio at the weld toe provides good agreement between the experimentally and analytically found S–N curves. The effect of the residual stress was successfully included in the analysis.  相似文献   
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