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L J Nugent

Publications and source records attributed to L J Nugent.

6 recordsLinked to original sources
PubMed1984

Two-compartment model for plasma pharmacokinetics in individual blood vessels.

Plasma pharmacokinetics of sodium fluorescein, fluorescein isothiocyanate conjugated bovine serum albumin, and a graded series of dextrans of 19,400 to 71,800 MW were monitored continuously using a noninvasive photometric technique in individual blood vessels of tissue grown in a rabbit ear chamber. The data obtained were fitted with a two-compartment open model to obtain an effective permeability and an effective clearance. Both parameters decreased with increasing molecular radius for dextrans. Values for albumin were considerably less than expected on the basis of molecular radius, presumably due to the configuration, charge, and binding characteristics of albumin.

Animals↗
PubMed1984

Plasma pharmacokinetics and interstitial diffusion of macromolecules in a capillary bed.

Concentration-time profiles of fluorescein isothiocyanate (FITC)-conjugated bovine serum albumin and a graded series of FITC-dextrans of 20,000-70,000 molecular weight were measured within the erythrocyte-free plasma layer in individual vessels and at various positions within the interstitial tissue space of mature granulation tissue grown in a rabbit ear chamber. Sodium fluorescein was used as a representative small molecule. The plasma pharmacokinetic data were found to follow a biexponential decay in time. A one-dimensional model of diffusion adequately described interstitial transport. Interstitial diffusion coefficients decreased progressively with Stokes-Einstein radius with values for albumin being significantly reduced from that for a dextran of equivalent hydrodynamic radius. Interstitial diffusion of sodium fluorescein and albumin agreed with a fiber-matrix model, whereas the interstitial diffusion of dextrans more closely corresponded to a pore model.

Capillaries↗
PubMed1984

Extravascular diffusion in normal and neoplastic tissues.

Extravascular transport of fluorescein isothiocyanate-conjugated bovine serum albumin and a graded series of fluorescein isothiocyanate-dextrans from Mr 19,400 to 71,800 were studied in both normal tissue (granulation) and tumor (VX2 carcinoma) grown in a rabbit ear chamber. Sodium fluorescein was used as a representative small molecule. A one-dimensional diffusion model adequately described extravascular transport in both normal and tumor tissue. Measured diffusion coefficients showed a relationship with molecular size which progressively deviates from that of free diffusion in water, with values for albumin being significantly reduced from that for a dextran of equivalent size. Macromolecular transport in tumor tissue was hindered to a lesser extent than in normal tissue, which is consistent with reports of reduced contents of glycosaminoglycans, and markedly large interstitial space in tumors. Diffusion coefficients for dextran were found to vary with molecular weight according to the expression, D = a(Mr)b, in both normal tissue (a = 10(6) and b = -2.96) and tumor (a = 2.51 X 10(-2) and b = 1.14).

Animals↗
PubMedDate not supplied

Dose maintenance for Partial Liquid Ventilation: passive heat-and-moisture exchangers.

Partial Liquid Ventilation (PLV), a promising method for the treatment of acute lung failure, has been evaluated in many animal studies. It has recently progressed to the point of controlled clinical trials in which patients of all ages on conventional mechanical ventilation (CMV) have their lungs substantially filled with a perfluorochemical (PFC) liquid, perflubron (PFB). During PLV, it is desirable to both maintain humidification and minimize the evaporation of PFB in order to maintain a desired dose in the lung and to reduce dose consumption and redosing effort. Heat-and-moisture exchangers (HMEs) have been used for years as a passive means of minimizing water vapor loss from the respiratory tract during CMV support of intensive care and surgical patients. In the current study, research was undertaken to leverage the operating principles of existing HMEs such that specialized "fluorophilic" HMEs (FHMEs), devices optimized for both water and PFB conservation, could be realized. A patient simulator (involving both water vapor and PFB vapor sources) was constructed and used in the in-vitro evaluation of various FHME concepts. Dose-retention efficiencies were determined with the aid of an infrared instrument and a digital thermohygrometer. Although no larger than commercial HMEs in terms of dead space (gas-occupying volume), efficient FHMEs resulted, offering less flow resistance (delta P) than their commercial counterparts. Additionally, the presence of PFB vapor did not appear to compromise the water-exchange efficiency of certain HME configurations. One promising FHME design was also tested in swine undergoing 12-hour PLV treatments. A mean conservation efficiency of 63% at an average tidal volume of 550 mL was shown, although somewhat lower efficiencies may result in adult patients because efficiency was found to trend downward with increasing tidal volume. The use of an FHME is expected to sustain dose levels in patients for longer periods with less frequent dosing and reduced dose consumption, saving treatment labor and cost.

Adult↗