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Biomedical subjects

J L Bert

Publications and source records attributed to J L Bert.

At least 19 recordsLinked to original sources

Modeling transient exchange in mesentery.

In this paper, a mathematical model of interstitial transport and microvascular exchange within a rigid mesenteric tissue segment is employed to simulate the transient exchange of fluid and plasma proteins following two systemic disturbances: hypoproteinemia and venous congestion. In each case, the model system behavior is studied as a function of interstitial plasma protein transport mechanisms and mesothelial transport properties. Plasma protein washout was generally predicted in cases of hypoproteinemia. However, following venous congestion, the transient change in interstitial plasma protein content also depended on the relative sieving properties of the filtering and draining boundaries. When these boundaries display similar sieving characteristics, the interstitial plasma protein content increases following the disturbance. Such behavior may have some bearing on transient exchange in the hepatic microcirculation during venous congestion.

Biological Transport

Mechanical properties of human tracheal cartilage.

Biomechanical changes in airway cartilage could influence the mechanics of maximal expiratory flow and cough and the degree of shortening of activated airway smooth muscle. We examined the tensile stiffness of small samples of human tracheal cartilage rings in specimens obtained at autopsy from 10 individuals who ranged in age from 17 to 81 yr. The tensile properties of the cartilage were compared with its content of water (%water), glycosaminoglycans (chondroitin sulfate equivalents, mg/mg dry wt), and hydroxyproline content (mg hydroxyproline/mg dry weight). The average values for tensile stiffness ranged between 1 and 15 MPa and increased significantly with increasing age [tensile stiffness = 0.19 x (age in yr) + 2.02; r = 0.83, P less than 0.05]. The outermost layer of cartilage was the most stiff in all individuals, and the deeper layers were progressively less stiff. Water content and hydroxyproline content both decreased with increasing age. Thus tensile stiffness correlated inversely with water content and hydroxyproline content [tensile stiffness = -0.83 x (%water) + 16.4; r = 0.82, P less than .05 and tensile stiffness = -342 x (hydroxyproline content) + 25; r = 0.87, P less than 0.05]. Total tissue content of glycosaminoglycans did not change with age, although changes in glycosaminoglycan type and proteoglycan structure with increasing age have been described. We conclude that there are age-related changes in the biomechanical properties and biochemical composition of airway cartilage that could influence airway dynamics.

Adolescent

Microvascular exchange during burn injury: IV. Fluid resuscitation model.

The present work is a continuation of studies concerned with mathematical modelling and simulation of microvascular fluid and protein exchange following burn injuries [Bert et al.: Circulatory Shock 28: 199-219, 1989: Bowen et al.: Circulatory Shock 28: 221-233, 1989]. The model has been extended to include the effects of different types of fluid resuscitation on the circulatory and microvascular exchange systems. The model and a statistical fitting procedure were used to find the ranges of fitting parameter values that best describe the changes in interstitial fluid volume and protein mass as well as transcapillary protein extravasation for three sets of experiments (no resuscitation, resuscitation with Ringer's or resuscitation with plasma). Typical changes in mass exchange related parameters postburn that resulted in simulation predictions which were a good fit to the experimental data include: an increase in the large pore pathway for protein of 100 times in the injured skin and 5 times in non-injured skin and skeletal muscle, an increase in fluid filtration coefficients in injured skin of 10 times and an instantaneous decrease of 50% in the area available for exchange in injured skin at the time of the burn.

Burns

A hierarchical coding system for occupational exposure.

A 10-digit hierarchical method for coding occupationally encountered chemicals offering significant advantages over existing chemical coding systems has been developed and tested. With this unique system, substances are categorized and coded according to their composition and physical natures. Consequently, compounds of similar structure may be distinguished, and classes of similar compounds (for example, all halogenated organic compounds, all inorganic sulfates) can be readily retrieved. This novel coding system was developed to assist primarily in the identification of potential carcinogens in occupational studies using job exposure matrices. However, the system has wider applications as it can be employed by industry to facilitate data management and monitoring programs in the workplace.

Carcinogens

A mathematical model of interstitial transport. I. Theory.

A generalized model is developed to describe the transport of fluid and plasma proteins or other macromolecules within the interstitium. To account for the effects of plasma protein exclusion and interstitial swelling, the interstitium is treated as a multiphase deformable porous medium. Fluid flow is assumed proportional to the gradient in fluid chemical potential and therefore depends not only on the local hydrostatic pressure but also on the local plasma protein concentrations through appropriate colloid osmotic pressure relationships. Plasma protein transport is assumed to occur by restricted convection, molecular diffusion, and convective dispersion. In a companion paper (D. G. Taylor, J. L. Bert, and B. D. Bowen, 1990, Microvasc. Res. 39, 279-306) a simplified version of the model is used to analyze steady-state fluid and plasma protein exchange within mesentery.

Animals

A mathematical model of interstitial transport. II. Microvascular exchange in mesentery.

A simplified version of the model of interstitial transport developed earlier (D. G. Taylor, J. L. Bert, and B. D. Bowen, 1990, Microvasc. Res. 39, 253-278) is used to investigate microvascular exchange of fluid and a single "aggregate" plasma protein species in mesenteric tissue. The interstitium is approximated by a rigid, rectangular, porous slab displaying two fluid pathways, only one of which is available to plasma proteins. The model is used to explore the effects of the interstitial plasma protein diffusivity, the tissue hydraulic conductivity, the restricted convection of plasma proteins, and the mesothelial transport characteristics on the steady-state distribution and transport of plasma proteins and flow of fluid in the tissue. The simulations predict significant convective plasma protein transport and complex fluid flow patterns within the interstitium. These flow patterns can produce local regions of high fluid and plasma protein exchange along the mesothelium which might be erroneously identified as "leaky sites."

Animals

A generalized model for the prediction of lead body burdens.

A compartmental model of a typical 70-kg male for lead intake, distribution, and transport has been developed based on previous pharmacokinetic models and experimental results for lead in the human body. A set of first-order, linear ordinary differential equations with constant coefficients is solved to predict lead levels in blood, bone, and other compartments as a function of time resulting from inputs from air and/or ingestion. The model has been shown to be in excellent agreement with the measurements of blood lead for a controlled study by M. B. Rabinowitz et al. (1976, J. Clin. Invest., 58, 260-270). Favorable agreement was also found with blood and urine results reported by T. B. Griffin et al. (1975, "Lead," pp. 221-240) providing that an allowance was made for an unmeasured input of lead, originating from smoking, snacks, etc. The predictions of the newly formulated model are compared with those of the established Bernard model (S. F. Bernard, 1977, Health Phys., 32, 44-46). Predictions of blood lead concentration for short periods (on the order of months) are fitted better by the new model, while both models predict similar behavior over the longer term (on the order of 5 years and greater).

Adult

Microvascular exchange and interstitial volume regulation in the rat: implications of the model.

The present work uses and extends a dynamic mathematical model [J. L. Bert, B. D. Bowen, and R. K. Reed. Am. J. Physiol. 254 (Heart Circ. Physiol. 23): H384-H399, 1988] to investigate microvascular exchange and interstitial fluid volume regulation in the rat. Alternative concepts of transcapillary exchange as well as other parametric changes were incorporated into the model. In all cases, predictions resulting from these changes did not describe the available experimental information as well as the original model. A sensitivity analysis of the model showed the microvascular exchange system to be well regulated near its normal steady-state conditions through passive readjustment of the forces participating in the volume regulation. The transient rates of fluid and protein exchange were studied in order to determine the mechanisms inherent in the model that lead to fluid volume regulation during episodes of increased venous pressure and hypoproteinemia. In addition to interstitial compliance, lymph flow characteristics, and washdown of interstitial proteins, it was found that the magnitude and direction of reabsorption played an important role in the regulation process. Edema was always associated with a permanent reversal of the reabsorptive flow.

Animals

Microvascular exchange during burn injury: II. Formulation and validation of a mathematical model.

A mathematical model of microvascular exchange in the rat following a burn injury was developed by extending an existing model of normal microvascular exchange to include perturbations characteristic of burn injuries without fluid resuscitation. The changes anticipated for small (10% body surface area) and large (40% body surface area) burns are incorporated systematically into the model until there is no improvement in the statistical fit of the simulation predictions with the experimental data of Lund and Reed (Circulatory Shock 20:91-104, 1986). The "best fit" perturbations for the small burn include the experimentally measured changes in mean arterial pressure and injured tissue pressure as well as changes to plasma protein and fluid transport coefficients in the injured tissue. The larger burn "best fit" simulation required changes to the plasma protein transport coefficients in the intact tissues as well as all of the changes listed above. The simulation results are compared with the available experimental information on burn injuries as well as with the specific data of Lund and Reed (Circulatory Shock 20:91-104, 1986).

Animals

Microvascular exchange during burn injury: III. Implications of the model.

The present work investigates the implications of the predictions of a dynamic mathematical model of microvascular exchange following a nonresuscitated burn injury in a rat (Bert et al.: Circulatory Shock 28:199-219, 1989). Transport coefficients, transmicrovascular pressures, and the resultant fluid and protein fluxes were examined in order to assess their quantitative importance to the dynamic behavior of small (10% body surface area) and large (40% body surface area) burns. Edema accumulation in the injured tissue is dependent not only on events occurring in that tissue but is influenced strongly by interaction with the plasma and the noninjured tissue compartments.

Animals

Microvascular exchange and interstitial volume regulation in the rat: model validation.

A dynamic mathematical model is formulated and used to describe the distribution and transport of fluid and plasma proteins between the circulation, interstitial space of skin and muscle, and the lymphatics in the rat. Two descriptions of transcapillary exchange are investigated: a homoporous "Starling model" and a heteroporous "plasma leak model." Parameters used in the two hypothetical transport mechanisms are determined based on statistical fitting procedures between simulation predictions and selected experimental data. These data consist of interstitial fluid volume and colloid osmotic pressure measurements as a function of venous pressure for muscle and interstitial colloid osmotic pressure vs. venous pressure for skin. The values determined for the transport parameters compare well with data in the literature. The fully determined model is used to simulate steady-state conditions of hypoproteinemia, overhydration, and dehydration, as well as the dynamic response to changes in venous pressure and intravascularly administered protein tracers. Comparisons between the simulation predictions and experimental data for these various perturbations are made. The plasma leak model appears to provide a better description of microvascular exchange.

Algorithms

Digital simulation of pulmonary microvascular exchange.

A previously published analog computer simulation of blood to lymph fluid and protein transport in the human lung [Microvascular Research 27, 51-70 (1984)] has been converted to a digital program. Comparisons have been made between the predictions of the two programs for both transient and steady state responses to perturbations. The advantages of each program are discussed. The FORTRAN simulation, including the input and output files are explained. Copies of the program will be made for anyone who wishes to use it.

Body Fluids

Concentration of plasma albumin in its accessible space in postmortem human dermis.

This study was designed to measure the effective concentration of plasma albumin in the interstitial space of human dermis. Discs of tissue taken postmortem from four donors have been separately analyzed for their content of plasma albumin and equilibrated with 125I-labeled monomeric plasma albumin in a specially designed cell which limited tissue swelling. The equilibrated discs and their surrounding fluid were assayed for radioactivity and the tissue space accessible to albumin was calculated after correction for swelling. The albumin content of serum was also measured. The concentration of albumin in the accessible space of the tissue ranged from 0.45 to 0.93 that in serum, averaging 0.68. The fraction of the total interstitial fluid accessible to albumin averaged, for three normal dermises, 0.35 and for an overhydrated specimen, 0.51. Thus, the effect of volume exclusion should be considered in measurements of the concentrations of plasma proteins in tissue.

Blood Proteins