A Fluid Dynamic Analysis Using Flow Visualization of the Baylor/NASA Implantable Axial Flow Blood Pump for Design Improvement

Abstract: The Baylor/NASA Axial Blood Flow Pump has been developed for use as an implantable left ventricular assist device (LVAD). The pump is intended as an assist device for either pulmonary or systemic circulatory support for more than 3-months' duration. To date the pump provides acceptable results in terms of thrombus formation and hemolysis (IH of 0.018 g/100 L). A fluid dynamics analysis using flow visualization was performed to investigate the flow fields and to determine areas within the pump that could be improved. These studies focused upon the inflow area in front of the pump. A prototype axial flow pump assembly was constructed to facilitate the flow visualization studies. Particle image tracking velocimetry techniques were used to measure Amberlite particles suspended in a blood analog fluid composed of 63% water and 37% glycerin. This method used a pulsed (612 Hz) laser light to determine flow velocity profiles, shear stress, Reynolds numbers, and stagnant areas within the axial pump. These studies showed that the flow straightener (a vaned assembly in the pump inflow) reduced Reynolds numbers from 4,640 to 2,540 (at 8.5 L/min) and that the flow straightener exacerbates a discontinuity found between it and the impeller. Within the inflow area, a maximum of 80 N/m² shear stress was measured, which is well below published blood damage thresholds. Design variations were investigated resulting in a smoother flow transition between flow straightener and impeller. These variations must be investigated further to establish a correlation with hemolysis and thrombus formation.     

Light-directed synthesis of high-density oligonucleotide arrays using semiconductor photoresists

High-density arrays of oligonucleotide probes are proving to be powerful new tools for large-scale DNA and RNA sequence analysis. A method for constructing these arrays, using light-directed DNA synthesis with photoactivatable monomers, can currently achieve densities on the order of 10⁶ sequences/cm². One of the challenges facing this technology is to further increase the volume, complexity, and density of sequence information encoded in these arrays. Here we demonstrate a new approach for synthesizing DNA probe arrays that combines standard solid-phase oligonucleotide synthesis with polymeric photoresist films serving as the photoimageable component. This opens the way to exploiting high-resolution imaging materials and processes from the microelectronics industry for the fabrication of DNA probe arrays with substantially higher densities than are currently available.     

Age-related changes in potassium-evoked overflow of dopamine in the striatum of the rhesus monkey

Rapid (5Hz) chronoamperometric recordings using Nafion-coated carbon fiber electrodes (30–90 microns o.d.) combined with pressure-ejection of potassium from micropipettes were used to investigate potassium-evoked overflow of dopamine (DA) in the striatum of young (5 to 10 years old) and middle-aged (19 to 23 years old) anesthetized rhesus monkeys. The potassium-evoked DA-like signals from the 19- to 23-year-old animals were significantly lower in amplitude than those recorded in the young animals. In addition, the temporal dynamics of DA signals in the caudate nucleus of middle-aged animals were faster, while the time courses of the signals recorded in the putamen of middle-aged monkeys were significantly longer as compared to the signals recorded from young animals. Moreover, home cage activity levels of the middle-aged animals were significantly lower. Taken together, these data support age-related changes in the output of DA from DA fibers in the striatum of middle-aged monkeys.     

Sequential, single-dose pharmacokinetic evaluation of meropenem in hospitalized infants and children.

Meropenem is a new carbapenem antibiotic which possesses a broad spectrum of antibacterial activity against many of the pathogens responsible for pediatric bacterial infections. In order to define meropenem dosing guidelines for children, an escalating, single-dose, pharmacokinetic study at 10, 20, and 40 mg/kg of body weight was performed. A total of 73 infants and children in four age groups were enrolled in the study: 2 to 5 months, 6 to 23 months, 2 to 5 years, and 6 to 12 years. The first patients enrolled were those in the oldest age group, who received the lowest dose. Subsequent enrollment was determined by decreasing age and increasing dose. Complete studies were performed on 63 patients. No age- or dose-dependent effects on pharmacokinetic parameter estimates were noted. Mean pharmacokinetic parameter estimates were as follows: half-life, 1.13 +/- 0.15 h; volume of distribution at steady state, 0.43 +/- 0.06 liters/kg; mean residence time, 1.57 +/- 0.11 h; clearance, 5.63 +/- 0.75 ml/min/kg; and renal clearance, 2.53 +/- 0.50 ml/min/liters kg. Approximately 55% of the administered dose was recovered as unchanged drug in the urine during the 12 h after dosing. No significant side effects were reported in any patients. By using the derived pharmacokinetic parameter estimates, a dose of 20 mg/kg given every 8 h will maintain plasma meropenem concentrations above the MIC that inhibits 90% of strains tested for virtually all potentially susceptible bacterial pathogens.     

Pharmacokinetics of a novel 5-lipoxygenase inhibitor (ABT-761) in pediatric patients with asthma

Objective: The pharmacokinetics of an N-hydroxyurea analog, ABT-761 in asthmatic pediatric patients with asthma were investigated. Methods: A total of 24 patients were enrolled into this 8-day single- and multiple-dose study. Patients received daily doses of ABT-761 according to their body weight: patients of 20–38?kg received 50?mg; patients >38?kg but ≤55?kg received 100?mg, and patients ≥55?kg received 150?mg. Results: The mean values for the terminal phase t_1/2 were 16–17?h after multiple-dose administration. When normalized for body weight, the mean day 8 Cl_f values for 50-, 100-mg, and 150-mg doses were 0.57 (n?=?13), 0.51 (n?=?10), and 0.43 (n?=?1) ml?·?min^?1?·?kg^?1, respectively, while the mean V_z/f values ranged from 0.75 to 0.77?l?·?kg^?1. The mean accumulation ratio observed (day 8 to day 1 AUC_0–24 ratio) of ABT-761 was approximately 1.7, which is consistent with the t_1/2 of this drug. Body weight, age, and body surface area were virtually identical in explaining the variability in dose-normalized C_max and AUC values (R ²?=?0.61–0.68). The percents of variance explained by these three variables were within a range of 3% for each pharmacokinetic parameter. Conclusions: The pharmacokinetics of ABT-761 in children were similar to those previously reported in adults. Body weight, age, or body surface area can be used to provide dosing adjustment for ABT-761 in pediatric patients.