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Biomedical subjects

E F Leonard

Publications and source records attributed to E F Leonard.

At least 19 recordsLinked to original sources
PubMed1994

Adsorption of proteins out of plasma onto glass from a separated flow.

Perturbations in the adsorption of plasma proteins caused by flow separation were studied quantitatively. An instrument was constructed that causes flow to separate over approximately half the width of a standard microscope slide and the pattern of protein deposition in and near the separated flow was observed by staining the slide with black iron oxide. The slide was mounted at the edge of a Couette flow field established between two concentric cylinders, the outer of which was rotating. The slide was located on the stationary, inner cylinder just downstream of a rectangular bar that causes the flow to separate. After exposure to dilute plasma injected upstream of the bar, the slide was removed and stained with oxide suspension. The resulting, visible pattern was scanned through a video camera and analyzed to yield relative values of stain density that could be quantified. The oxide patterns suggest that proteins were deposited onto the slide less rapidly in and just downstream of the separated flow region than farther downstream. At a shear rate of 6.61 s-1, corresponding to a velocity of 1.32 cm s-1 0.2 cm above the point of flow separation, overall amounts of adsorbed proteins increased with exposure time in the range 3-30 min with the exception of a period from 10 to 11 min when all data show a temporary decrease. In calibration experiments, oxide failed to adhere to slides exposed to purified albumin but adhered copiously to slides exposed to purified fibrinogen. These results suggest that the oxide patterns following plasma exposure are attributable primarily to fibrinogen and that the temporary decrease in the separated flow experiments is attributable to the displacement of fibrinogen by a less stainable protein, conjecturally high molecular weight kininogen and factor XII. This study yields quantitative information confirming earlier findings that were less controlled and non-quantitative. It confirms the hypothesis that the sequence of protein deposition from dilute plasma to glass surfaces is delayed in regions of separated flow.

Adsorption↗
PubMed1991

Is the Vroman effect of importance in the interaction of blood with artificial materials?

The successive displacement of plasma proteins adsorbed to artificial surfaces (biomaterials) is well documented, mostly by specially designed experiments that stretch out the effect in time and space. Analysis of displacement has been focused principally on molecular events on the adsorbing surface. In this paper attention is directed rather to the antecedent transport phenomena necessary to deliver successive proteins to a surface. The different limitations on protein arrival fixed by the total quantity present and by the rates of transport of super-sufficient quantities are distinguished. The transport perspective is then used to ask, and partly answer, the question: Can protein displacement be responsible for patterns of thrombus formation and cellular adhesion that are seen on the blood-wetted surfaces of devices found in medical practice: artificial organs and vascular prostheses? Calculations and a small amount of preliminary data suggest that such patterns may form when blood is introduced into these devices, particularly in the neighborhood of boundary shapes that cause separated flows.

Adsorption↗
PubMed1990

Errors in estimates of peritoneal fluid volume.

Inherent limitations in the suitability of drainage volumes for monitoring intraperitoneal fluid volume have resulted in the frequent use of indicator dilution techniques, but little attention has been given to confirming the adequacy of the estimates that volume markers provide. In a series of experimental exchanges in rats, volume estimates were compared based on the dilution of blue dextran and hemoglobin with direct collections of surgically exposed intraperitoneal fluid. Significant systematic and random errors in the indicator dilution volume estimates were observed. The systematic errors appeared to be due to the rapid removal of a fixed amount of marker from peritoneal fluid, while the random errors were caused by the rapid appearance of a variable amount of endogenous chromogen. The behavior of the markers observed in this study was not consistent with the assumptions commonly used to analyze volume transport in peritoneal dialysis.

Animals↗
PubMed1988

The use of polyelectrolytes as osmotic agents for peritoneal dialysis.

Various small and large molecules have been studied as osmotic agents to replace dextrose in peritoneal dialysis. Macromolecules are attractive because of their slow absorption from intraperitoneal solutions; however, it has been assumed that they are only marginally effective as osmotic agents unless they function as polyelectrolytes at physiological pH. In experimental exchanges conducted in rats we measured volume changes induced by Gelifundol (5.5% oxypolygelatin) and Ringers lactate to which was added either nothing, 4.25% dextrose, or 5% albumin. In the control exchanges using Ringers lactate, intraperitoneal fluid volume remained unchanged for eight hours. The volume changes induced by 4.25% dextrose were complete within two hours and resulted in a two-thirds increase over the amount of fluid administered. In both series in which polyelectrolytes were used volume transport was sustained throughout an eight hour dwell. With 5% albumin the total increase in fluid volume was about 40% of that installed, while Gelifundol caused fluid volume to double. Qualitatively similar results were obtained in transport studies conducted in vitro. Physical studies of the oxypolygelatin solutions indicated that the fixed charges per liter were comparable to those in the albumin solutions. Thus the different volume transport the two proteins induced could not be attributed to Donnan effects. However, since the molecular weight of albumin is triple that of Gelifundol the van't Hoff pressures of the two macromolecules can explain the observed differences in volume transport. These results suggest that neutral macromolecules deserve further study as potential osmotic agents for peritoneal dialysis.

Albumins↗
PubMed1985

Formulating and evaluating quantitative models of control of sodium stores.

Numerous factors that influence sodium handling have been identified, and many have been studied in minute detail; however, relatively little information is available regarding either the steady-state relationship between dietary sodium intake and sodium stores or the transient response of intact animals to challenges to sodium homeostasis. In this paper the principles of elementary feedback control theory have been used both to obtain and analyze quantitative models of the feedback control of sodium stores. It has been assumed that the sodium content of the body determines the rate of urinary sodium excretion, and a mass balance has been used to obtain differential equations that describe the dynamics of sodium stores. Both first- and second-order models are considered, and their predictions for both steady states and transients are compared critically with observations from the literature, using data from human studies whenever possible. The results indicate that a relatively simple proportional feedback controller describes most available data well; however, gaps in the available information are identified, and opportunities for future experimental investigation are described.

Feedback↗
PubMed1985

Dialysis membranes.

Explore the source record for details and available documents.

Biocompatible Materials↗
PubMed1984

A graph theory model of the glomerular capillary network and its development.

Graph theory methods were used to analyze the topology of the renal glomerular capillary network using data both from a serial reconstruction of a rat glomerulus and from the literature. The graphs obtained were tested for planarity, and all but one were found to be nonplanar. This result indicated that the development of the glomerular capillary network must include a nonplanar growth process, and new growth models were proposed. In addition, the statistical properties of capillary branching patterns were analyzed, and a node degree distribution function estimate was obtained.

Animals↗
PubMed1984

Glucose and glycerol compared as osmotic agents for peritoneal dialysis.

The potential utility of glycerol as an osmotic agent for peritoneal dialysis was evaluated by conducting both isosmotic and hyperosmotic exchanges in anesthetized rats. Similar exchanges were conducted using glucose, and the results with the two agents were compared. During hyperosmotic exchanges both agents produced significant osmotic flow of water, but at initial molar concentrations that were equal the flow observed with glycerol was nearly 40% less than that observed with glucose. The lower volume transport generated by glycerol was found to be due to its surprisingly rapid removal from peritoneal fluid when it was present at hyperosmotic concentrations, but paradoxically during isosmotic exchanges, when its concentration was low, glycerol was absorbed only slightly faster than glucose. The observed increase in peritoneal permeability when glycerol was used resulted in a twofold increase in the caloric load imposed per unit of water removed in comparison with glucose.

Absorption↗
PubMed1984

The use of hemoglobin solutions in kidney perfusions.

Solutions of hemoglobin have often been considered for both hypothermic and normothermic perfusion of isolated kidneys. This paper considers basic issues, preparative techniques, and the viscosity of hemoglobin solutions, as well as the demands made by the kidney on a perfusate. The natural system of oxygen transport in higher animals is complex, and its perturbation to produce convenient hemoglobin-based renal perfusates produces numerous problems. The desirable effect of 2,3-diphosphoglycerate is not easily maintained in a perfusate, but its inclusion can be avoided by appropriate choice of species donating hemoglobin. Hemoglobin tetramer in free solution may dissociate and be lost by glomerular filtration. Ferric hemoglobin, the dominant form at redox equilibrium, is useless for oxygen transport; the ferrous form is maintained in the erythrocyte by reducing metabolites and, under normothermic conditions, the ferrous to ferric conversion is slow but significant. Methods for lysis of erythrocytes and removal of their stroma are discussed; reduction of ferric hemoglobin by chemical agents and electrolysis are considered in detail; and means for adjusting concentration and solute background are presented. The need for carbonic anhydrase in hemoglobin solutions used as perfusates is shown and methods for its provision are discussed. A review of viscometric data for hemoglobin solutions is provided to which original data are added. Hemoglobin solutions show a temperature-independent intrinsic viscosity, according to Einstein's theory for a molecule of 23 A radius. The O2 and CO2 transport requirements of renal perfusates are analyzed comprehensively. The normothermic kidney has an unusual respiration pattern, requiring an amount of oxygen that is not fixed but, rather, proportional to the total blood flow rate. In canines the average arterio-venous O2 content difference found by many investigators is 2.14 vol%; the corresponding CO2 value is 2.47 vol%; and the respiratory quotient is greater than unity. Wide limits of PO2, but not P CO2 in perfusate, appear allowable. A final section evaluates hemoglobin solutions as both normothermic and hypothermic renal perfusates from the viewpoints of blood gas chemistry, urinary loss, oncotic pressure, fatty acid carrying capacity, viscosity, and the need for functions usually attributed to platelets. It is concluded, overall, that perfusates containing free hemoglobin have only a limited role to play in renal perfusion.

Animals↗
PubMed1983

Bloodless evaluation of blood oxygenators.

Evaluation of blood oxygenators using whole blood is inconvenient and expensive, although it is the ultimate preclinical test. Sodium sulfite solutions have advantages over blood for studying oxygen uptake: They are inexpensive, fewer variables need control, and deoxygenation is unnecessary. Assays and interpretation of results are easy. The kinetics of sulfite oxidation must be fast and the concentration of sulfite must be low to emulate oxygen uptake by blood. The kinetics were studied yielding a first order rate constant in sulfite, zero order in oxygen, of 740/min. Limitations of the technique were evaluated using the experimental rate constant and an adaptation of Lightfoot's approximation. While the reaction of hemoglobin is reversible and essentially instantaneous, that for sulfite is irreversible and finite. Thus if the approach to saturation is not monotonic or if the mass transfer resistance is significantly lowered, e.g., when blood film thicknesses are thinner than a few hundred microns, deviations may occur. Two TMO oxygenators and several prototypes were tested, with both sulfite and bovine blood. Uptakes of oxygen were comparable and the effect of parameter variations were similar. The use of sulfite for early evaluation of oxygenators is concluded to be very useful.

Animals↗