Infusion optimization

Compared to streptokinase, urokinase has been less extensively studied because of its high cost, ie, about 10 times that of a comparable treatment with streptokinase. In addition to the indications described for streptokinase, urokinase is indicated for use in patients with prior streptokinase treatment, or prior Streptococcal infection. Urokinase is commonly used at a loading dose of 4400 units /kg, with a maintenance intravenous infusion dose of 4400 units/kg/h for thromboses other than acute myocardial infarction. In the latter case, a much larger dose, ie, 0.5—2.0 million units/h or a bolus dose of 1.0 million units followed by a 60-min infusion with 1.0 million units, has been found optimal (106). An intracoronary dose of 2000 units/min for two hours was used in one comparative study with intracoronary streptokinase (107). In this study, urokinase exhibited efficacy equivalent to streptokinase with fewer side effects. Other studies with intracoronary urokinase have adrninistered doses ranging from 2,000 to 24,000 units/min with a reperfusion efficacy of 60—89% (108—112). In another urokinase trial, 2.0 million units were adrninistered intravenously, resulting in a thrombolytic efficacy of 60% (113). Effectiveness in terms of reduction in mortaUty rate has not been deterrnined because of the small number of patients studied. 

The result of taking into account the three factors mentioned - dose - degree of comminution - method of extraction - should be a tea that has an optimal amount of active constituents. But, at present ihere are very few studies which answer the often posed question What proportion of the active principles in the drug pass over into the tea With a hot-watcr infusion of chopped senna... 

MONITORING DRUGS GIVEN INTRAVENOUSLY. For optimal results, die nurse inspects the needle site and die area around die needle every hour for signs of extravasation of die IV fluid. The nurse performs diese assessments more frequently if the patient is restiess or uncooperative It is important to check the rate of infusion every 15 minutes and adjust it as needed. The nurse should inspect die vein used for die IV infusion every 4 hours for signs of tenderness, pain, and redness (which may indicate phlebitis or thrombophlebitis). If tiiese are apparent, die nurse must restart the IV in another vein and bring the problem to the attention of the primary health care provider. 

Promoting an Optimal Response to Therapy Fhtients receiving an IV fluid should be made as comfortable as possible, although under some circumstances this may be difficult. The extremity used for administration should be made comfortable and supported as needed by a small pillow or other device An IV infusion pump may be ordered for the administration of these solutions. The nurse sets the alarm of the infusion pump and checks the functioning of the unit at frequent intervals. 

The MS/MS response for each analyte must first be optimized on the specific instrument to be used. This is usually done by infusing a solution of the analyte into the HPLC mobile phase without a column present. The composition of the mobile phase should match that expected at the time of analyte elution within 25%. The instrument is first operated in the LC/MS mode, and the settings for the electrospray interface are... 

InsAument parameters (sheath and auxiliary gas flows, spray voltage, capillary temperature, collision cell gas flow and offset, etc.) should be optimized while infusing a standard of tebuconazole prior to the Arst attempt at analysis. Optimization should be performed at an HPLC Aow rate and composition simulating those present during elution of tebuconazole using each HPLC condition set employed... 

The optimal infusion rate is dependent on the volemic and hemodynamic status of the patient... 

Insulin pump therapy consists of a programmable infusion device that allows for basal infusion of insulin 24 hours daily, as well as bolus administration following meals. As seen in Fig. 40-3, an insulin pump consists of a programmable infusion device with an insulin reservoir. This pump is attached to an infusion set with a small needle that is inserted in subcutaneous tissue in the patient s abdomen, thigh, or arm. Most patients prefer insertion in abdominal tissue because this site provides optimal insulin absorption. Patients should avoid insertion sites along belt lines or in other areas where clothing may cause undue irritation. Infusion sets should be changed every 2 to 3 days to reduce the possibility of infection. 

After performing a nutrition assessment and estimating nutritional requirements, determine the optimal route to provide specialized nutrition support (e.g., oral, enteral, or parenteral). If PN is deemed necessary, venous access (i.e., peripheral or central see below) for PN infusion must be obtained. Finally, formulate a PN prescription, and administer PN according to proper safety guidelines. 

The Marshall group has optimized reaction (14) to obtain a poly-si lazane with Mw A000 Daltons which can be hand drawn to give 10-20 pm preceramic fibers. These fibers are then rendered Infusible by exposure to humid air and pyrolyzed to give fibers with the same ceramic yields, 55+%, as found by Verbeek et al. The ceramic products are mainly amorphous SiC and SijN with some Si02 (a consequence of the humidity treatments). 

Castrillo, J. L. Hayes, A. Mohammed, S. Gaskell, S. J. Oliver, S. G. An optimized protocol for metabolome analysis in yeast using direct infusion electrospray mass spectrometry. Phytochemistry 2003, 62, 929-937. 

One-time doses are optimally infused at induction of anesthesia except as noted. Repeat doses may be required for long procedures. Strength of recommendations ... 

The multiple reaction monitoring (MRM) conditions for each analyte were optimized by infusing 0.1 jxglmL of analyte in mobile phase. The Ionspray needle was maintained at 4.0 kV and the turbo gas temperature was 650°C. Nebulizing gas, auxiliary gas, curtain gas, and collision gas flows were set at 35, 35,40, and 4, respectively. In the MRM mode, collision energies of 17,16, and 15 eV... 

One issue related to supporting a metabolic stability assay with HPLC/MS/MS is the need to set up an MS/MS method for each compound. While it may only take 10 min to infuse a compound solution and find the corresponding precursor and product ions (along with minimal optimization of the collision energy), the processes of MS/MS development would require 4 hr per day if one wanted to assay 25 compounds per day. MS vendors have responded to this need by providing software tools that can perform the MS/MS method development step in an automated fashion. Chovan et al.68 described the use of the Automaton software package supplied by PE Sciex (Toronto, Canada) as a tool for the automated MS/MS method development for a series of compounds. The Automaton software was able to select the correct precursor and product ions for the various compounds and optimize the collision energy used for the MS/MS assays of each compound. They found that the Automaton software provided similar sensitivity to methods that would have been developed by manual MS/MS procedures. Chovan et al. also reported that the MS/MS method development for 25 compounds could be performed in about an hour with the Automaton software and required minimal human intervention. 

QuanOptimize from Micromass also allows automated method development for quantitative LC/MS/MS. It automatically identifies the best method for each compound, then runs batches of samples for quantitative analyses and report results in a QuanLynx browser. Thermo recently launched a similar product for automatic MS tuning. Known as QuickQuan, it generates data and stores it in a central Microsoft Access or Oracle database for future access. The infusion-based valve switching auto-tuning device allows individual compounds to be fully and automatically optimized in about 1 min. 

Alternatively, direct methods (syringe infusion, flow injection) can be used as a preliminary step in determining the optimal MS detector conditions for particular molecules. This is especially useful when the MS is attached to a liquid chromatograph, in which the fluid entering the MS will vary with gradient elutions (varied solvent and salt compositions) or with sample types (varied sample matrices, extraction solvents, included salts, etc.), which can affect the predominant ion type and sensitivity, or produce other matrix effects such as ion suppression or extraneous signals. 

Either the information obtained during the data-dependent acquisition is sufficient or a fraction of interest can be re-analyzed by chip-based infusion at a flow rate ca. 200 nl min. Due to the miniaturization sample consumption is very low (typically 1-3 pi) and acquisition time is no longer critical. Therefore various MS experiments can be performed on various instruments, including MS and accurate mass measurements. An additional advantage is that the eluent can be removed and the infusion solvent can be optimized for positive or negative ion detection or for deuterium exchange measurements. 

Different organic and inorganic buffers, such as ammonium acetate, ammonium formate, HEPES, Gly-Gly, and triethanolamine, were selected to study the response of biotin and fluorescein-biotin in MS and compared to phosphate buffer. Biotin and fluorescein-biotin were dissolved in the carrier solution compositions of buffer (10 mM pH 7.5)/methanol (50 50, v/v) at concentrations of 10 ng pl k Both infusion and 20 pl-loop injection experiments were performed with detection by MS in full-scan and SIM mode. Main optimization criteria are the maximum response of biotin and fluorescein-biotin with lowest interference of the carrier solution. HEPES, Gly-Gly, and triethanolamine give very high background response, which significantly hampers the detection of biotin and fluorescein-... 

The above described principles imply that optimal therapy should include tumors that are 5-FU-sensitive or, in other words, are derived from normal tissues sensitive to infused... 

Practically speaking, 5-FU infused at 25-30 mg/kg/d continuously for 5 d will radiosensitize virtually all 5-FU-sensitive tumors listed in Table 1. Although the optimal regimen has yet to be established, the 5-d schedule of 5-FU currently appears close to an ideal regimen. 

The pharmacologic studies indicated that intrinsic pharmacokinetics of 5-FU hinder their ability to reproduce the conditions required for radiosensitization. Indeed, the short half-life of the drug (from hepatic removal) preclude anything other than addictive effects when bolus drug is added to any variety of radiation fractionation scheme. These two sets of requirements together demonstrated that a continuous infusion (in which drug is made present for at least 24 h after each radiation fraction) would be optimal. In summary, 5-FU is a potent radiosensitizer under the following defined circumstances. 

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