Joel L. Bert

Ultrastructure and tensile properties of human tracheal cartilage.

The cartilage of the walls of the trachea and bronchi acts to keep these airways open despite intrathoracic pressure differences during breathing that would otherwise collapse them and limit air flow. Changes in biomechanical properties and composition of airway cartilage may contribute to altered lung function in obstructive lung diseases. To investigate the relationship between collagen organization and equilibrium tensile modulus within the structure of airway cartilage, we used scanning electron microscopy (SEM), histochemistry and equilibrium tensile testing to analyze tracheal cartilage from 10 humans aged 17-81 yr. We show that the surfaces of tracheal cartilage matrix are collagen-rich and surround a proteoglycan-rich core. Collagen fibrils in the superficial zones are oriented in the plane of the cartilage surface. In deeper layers of the cartilage, collagen fibrils are oriented less regularly. Equilibrium tensile modulus of 100 microm thick strips of cartilage was measured and was found to decrease with depth; from 13.6 +/- 1.5 MPa for the ablumenal superficial zone to 4.6 +/- 1.7 MPa in the middle zone (means +/- S.D., n = 10, p < 0.001). Stress-strain curves were linear for strains up to 10% with minimal residual strain. This is consistent with a model in which collagen fibres in the outer layers of the cartilage resist tensile forces, and hydrated proteoglycans in the central zone resist compression forces as the cartilage crescent bends.

Prostate cancer risk and exposure to pesticides in British Columbia Farmers

Several epidemiologic studies have reported an increased risk of prostate cancer among farmers. Our aim was to assess the risk of developing prostate cancer in relation to exposure to specific active compounds in pesticides.

Modeling of occupant-generated CO2 dynamics in naturally ventilated classrooms

A numerical method is presented to estimate the concentration of occupant-generated CO2 for the (time-varying) occupancy typically found in nonforced ventilated elementary school classrooms. Here, the governing mass balance was solved numerically and compared to experimental measurements in order to estimate the respiration and (time-varying) infiltration rates. For the cases studied, we estimate an average CO2 generation rate per child as 404 mg/min−1. This is similar to estimates found in the literature for the age and activity level of elementary students, the classroom occupants. The average estimated infiltration rates were found to be larger than those measured from the decay of the tracer gas SF6 under closed-door static conditions. The in-use infiltration rates were increased by additional air exchange due to people entering and leaving the room. In addition, we show that the difference (or error) between the instantaneous concentration of CO2 and the time-averaged value recorded by a data-logging CO2 monitor varies depending on the infiltration rate and sampling time. Therefore, the time interval selected for averaging may increase the overall error of the apparent CO2 concentration. We conclude that the methods used to measure air exchange rates in naturally ventilated rooms underestimate the actual ventilation rate of a room under “in-use” conditions. However, even with the addition of uncontrolled outdoor air, the concentration of CO2 in the classrooms studied was higher than recommended to meet air quality objectives.

A heat transfer model of thermal balloon endometrial ablation.

AbstractA heat transfer model was developed for thermal balloon endometrial ablation treatment for menorrhagia. The model includes heat conduction through the uterus wall, cooling due to blood perfusion through the uterine tissue and the contribution of metabolic heat generation. A parameter sensitivity study indicated that metabolic heat generation had a minimal effect, but model predictions were sensitive to blood perfusion rate. However, within the range of expected perfusion rates, the model calculates damage depths (3–6 mm) close to the range for effective treatment. Using a blood perfusion rate of 0.0028 mt3 mb-3 ss-1 the predicted burn depth (4 mm) correlated well with experimental measurements (4.2 ± 0.6 mm) reported elsewhere for a treatment temperature of 92°C and time of 6 mins (Neuwirth, R. S. et al. The endometrial ablator: A new instrument. Obstet. Gynecol. 83:792–796, 1994). If no vaporization of water in the tissue occurs, the model predicts that the same burn depth of 4 mm can be obtained with increased treatment temperature (130°C) and shorter treatment time (1.4 min). Steeper temperature profiles through the uterine wall suggest that, in the absence of other changes due to higher temperatures, the deeper layers of the myometrium and the serosa would be protected from thermal damage when using higher treatment temperatures for a shorter duration. However, if vaporization occurs at 105°C, the model predicts little benefit in using treatment temperatures above 120°C up to 160°C. For further validation of the model, in vivo studies using the high temperature treatments are needed to measure temperature profiles through the uterine wall, blood perfusion rates, and the other effects of temperature on uterine tissue.

Dynamic evaluation of fluid shifts during normothermic and hypothermic cardiopulmonary bypass in piglets

Background: Edema, generalized overhydration and organ dysfunction commonly occur in patients undergoing open‐heart surgery using cardiopulmonary bypass (CPB) and induced hypothermia. Activation of inflammatory reactions induced by contact between blood and foreign surfaces are commonly held responsible for the disturbances of fluid balance (“capillary leak syndrome”). We used an online technique to determine fluid shifts between the intravascular and the interstitial space during normothermic and hypothermic CPB.

Studies on fluid extravasation related to induced hypothermia during cardiopulmonary bypass in piglets.

Background: Hypothermia, commonly used for organ protection during cardiopulmonary bypass (CPB), has been associated with changes in plasma volume, hemoconcentration and microvascular fluid shifts. Fluid pathophysiology secondary to hypothermia and the mechanisms behind these changes are still largely unknown. In a recent study we found increased fluid needs during hypothermic compared to normothermic CPB. The aim of the present study was to characterize the distribution of the fluid given to maintain normovolemia. In addition, we wanted to investigate the quantity and quality of the fluid extravasated during hypothermic compared to normothermic CPB.

Transport of fluid and solutes in the body I. Formulation of a mathematical model

A compartmental model of short-term whole body fluid, protein, and ion distribution and transport is formulated. The model comprises four compartments: a vascular and an interstitial compartment, each with an embedded cellular compartment. The present paper discusses the assumptions on which the model is based and describes the equations that make up the model. Fluid and protein transport parameters from a previously validated model as well as ionic exchange parameters from the literature or from statistical estimation [see companion paper: C. C. Gyenge, B. D. Bowen, R. K. Reed, and J. L. Bert. Am. J. Physiol. 277 ( Heart Circ. Physiol. 46): H1228-H1240, 1999] are used in formulating the model. The dynamic model has the ability to simulate 1) transport across the capillary membrane of fluid, proteins, and small ions and their distribution between the vascular and interstitial compartments; 2) the changes in extracellular osmolarity; 3) the distribution and transport of water and ions associated with each of the cellular compartments; 4) the cellular transmembrane potential; and 5) the changes of volume in the four fluid compartments. The validation and testing of the proposed model against available experimental data are presented in the companion paper.

Effect of charge on interstitial distribution of albumin in rat dermis in vitro

At physiological pH, negatively charged glycosaminoglycans in the extracellular matrix may influence distribution volume of a probe. We hypothesized that by varying the probe charge we would be able to observe a graded response of available volume fraction. Human serum albumin (HSA) (isoelectric point (pI) 5.0) was made more positive by cationization. Using reaction times of 10, 45 and 60 min, cationized HSA (cHSA) with respective pIs of 6.5, 7.3 and 8.0 were made. After eight days of equilibration in a buffer containing labelled native HSA and cHSA, the distribution volumes were calculated relative to that of 51Cr‐EDTA, an extracellular tracer. The available volume in fully swollen dermis for native albumin relative to that of the extracellular tracer averaged 0.485 ± 0.008 (n= 49), with corresponding volumes for cHSA‐10 min, cHSA‐45 min and cHSA‐60 min of 0.554 ± 0.012 (n= 17), 0.647 ± 0.026 (n= 17) and 0.718 ± 0.021 (n= 12), respectively. Increasing the ionic strength of the bathing solution to 1 M NaCl, thereby screening the fixed charges of tissue elements and probes alike, resulted in similar available and thereby excluded volumes of native HSA and neutral cHSA‐45 min. These experiments suggest that fixed negative charges, most likely glycosaminoglycans, contribute significantly to interstitial exclusion of charged macromolecules, a phenomenon of importance for hydration of the interstitial fluid phase and therefore for body fluid balance. Moreover, the data indicate that previous findings of similar excluded volumes for the two differently sized major plasma proteins albumin (molecular mass 66 kDa) and IgG (molecular mass 160 kDa) may be explained by a more pronounced electrostatic repulsion of the former by the extracellular matrix.

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.

Occupational Risk Factors for Prostate Cancer Mortality in British Columbia, Canada

BACKGROUND Although prostate cancer is the most common life-threatening cancer among males in North America, relatively little is known about its etiology. We have conducted a proportional mortality study to generate hypotheses concerning occupational risk factors for the disease. METHODS Age standardized proportional mortality ratios (PMR) for prostate cancer were calculated for a total of 216 occupations and 88 industries. Separate calculations were done for all male deaths age 20 and up and for deaths that occurred during mens working lifetime (age 20-65). RESULTS Elevated mortality from prostate cancer was seen among business owners and managers (PMR = 110; 95% CI = 101-118), brokers (PMR = 184; 95% CI = 122-266), farmers and farm managers (PMR = 112; 95% CI = 105-120), and school teachers (PMR = 133; 95% CI = 101-174). Evaluation by industry shows elevated prostate cancer mortality in agriculture (PMR = 110; 95% CI = 103-118), financial institutions (PMR = 138, 95% CI = 112-170), and transportation equipment manufacture (PMR = 136; 95% CI = 109-168). CONCLUSIONS The findings suggest that workers in a number of occupations have elevated risks of prostate cancer including farmers and teachers. More detailed cohort and case-control studies, evaluating specific exposures are required before primary prevention programs in the workplace are feasible.