PubMed Health⌕ Search

Biomedical subjects

L D Homer

Publications and source records attributed to L D Homer.

At least 19 recordsLinked to original sources
PubMed1992

Multiple cold air exposures change oral triiodothyronine kinetics in normal men.

The influence of cold exposure on triiodothyronine (T3) kinetics was studied in 16 men before, during (biweekly), and after 80 (10/wk) cold (4 degrees C) air exposures. We used serum values before and up to 24 h after a pharmacological oral (o) dose of T3 [76.8 nmol (50 micrograms)] to calculate noncompartmental kinetic parameters. To assess the role of thyroxine (T4) and thyrotropin (TSH), we administered a replacement dose of T3 [46.0 nmol/day (30 micrograms)] to eight men (+T3 group) and placebo to eight others (-T3 group) for the 2-mo study. There was no group effect of T3 treatment (+T3) on oral total volume of distribution (TVdo), metabolic clearance rate (MCRo), or disposal rate (DRo). TVdo was not changed over the study. Cold increased MCRo by 5.4 +/- 2.0 l.day-1.m-2. DRo increased with cold by 10.2 +/- 4.4 nmol.day-1.m-2. Although serum TSH, total T4, and free T4 decreased by approximately 50% in the +T3 group, the changes in MCRo and DRo with cold were not different from those in -T3. We describe that human T3 kinetics are changed with brief repeated exposures to cold air and that these increases in MCRo and DRo do not appear to be dependent on TSH or T4.

Administration, Oral↗
PubMed1992

Predicting the time of occurrence of decompression sickness.

Probabilistic models and maximum likelihood estimation have been used to predict the occurrence of decompression sickness (DCS). We indicate a means of extending the maximum likelihood parameter estimation procedure to make use of knowledge of the time at which DCS occurs. Two models were compared in fitting a data set of nearly 1,000 exposures, in which greater than 50 cases of DCS have known times of symptom onset. The additional information provided by the time at which DCS occurred gave us better estimates of model parameters. It was also possible to discriminate between good models, which predict both the occurrence of DCS and the time at which symptoms occur, and poorer models, which may predict only the overall occurrence. The refined models may be useful in new applications for customizing decompression strategies during complex dives involving various times at several different depths. Conditional probabilities of DCS for such dives may be reckoned as the dive is taking place and the decompression strategy adjusted to circumstance. Some of the mechanistic implications and the assumptions needed for safe application of decompression strategies on the basis of conditional probabilities are discussed.

Decompression Sickness↗
PubMed1990

Xenon kinetics in muscle are not explained by a model of parallel perfusion-limited compartments.

Experimental tissue gas kinetics do not follow the prediction for a single stirred perfusion-limited compartment. One hypothesis proposes that the kinetics might be explained by considering the tissue as a collection of parallel compartments, each with its own flow, reflecting the tissue microcirculatory flow heterogeneity. In this study, observed tissue gas kinetics were compared with the kinetics predicted by a model of multiple parallel compartments. Gas exchange curves were generated by recording the time course of tissue radioactivity in the intact calf muscles of anesthetized ventilated dogs exposed to step function changes of 133Xe in the inspired air for 5-h periods. Microcirculatory flow heterogeneity in the same tissue was determined by the radioactive microsphere method. Observed mean tissue transit times were on average longer than predicted by a factor of 6.7. Observed means averaged 52.1 min compared with 8.3 min predicted by the perfusion-limited model. Relative dispersions of tissue transit times were also uniformly larger than predicted. We conclude that Xe gas kinetics in intact canine skeletal muscle are not explained by a model of multiple parallel perfusion-limited compartments. Countercurrent exchange of gas between vessels is a possible explanation.

Animals↗
PubMed1990

Bubble-induced dysfunction in acute spinal cord decompression sickness.

Five anesthetized dogs undertook a chamber dive, on air, to 300 feet of seawater for 15 min. After the dive, spinal cord decompression sickness was detected by recording a reduced amplitude of the somatosensory evoked potential compared with predive base-line values. After the diagnosis of decompression sickness and rapid perfusion fixation of the animal, the spinal cord was removed and examined histologically. Numerous space-occupying lesions (SOL) that disrupted the tissue architecture were found in each cord, mainly in the white matter. The size and distribution of the SOL were determined using computerized morphometry. Although SOL occupied less than 0.5% of the white matter volume, we tested a number of algorithms to assess whether the SOL may have been directly involved in the loss of spinal cord function that followed the dive. We determined that the loss of somatosensory evoked potential amplitude may be attributed to the SOL if 30-100% of the spinal cord fibers that they displaced were rendered nonconducting. A number of possible mechanisms by which SOL may interfere with spinal nerve conduction are discussed.

Animals↗
PubMed1990

How countercurrent blood flow and uneven perfusion affect the motion of inert gas.

Monte Carlo simulations of the passage of inert gas through muscle tissue reveal that countercurrent gas exchange is more important than heterogeneity of flow in determination of the shape of inert gas washout curves. Semilog plots of inert gas washout are usually curved rather than straight. Two explanations often offered are that countercurrent flow may distort the shape and that uneven perfusion of the tissue gives rise to nonuniform washout. The curvature of the semilog plot may be summarized by the relative dispersion (RD), which is the ratio of the standard deviation of transit times to the mean transit time. For straight semilog plots, RD is 1. Semilog plots of data showing xenon washout from dog tissues are curved and have and RD of approximately 2. We have simulated the transit of gas particles through a vascular bed composed of repeating units of 100 mg of tissue perfused by three small vessels 80 microns in diameter and several levels of branching that direct flow through 190,000 capillaries. Geometric distribution of flow is important. Similar degrees of flow heterogeneity affect the curvature of the washout curve more if regions of heterogeneous flow are widely spaced than if they are close together. Diffusion blunts the effects of heterogeneous flow by mixing particles in high-flow regions with particles in low-flow regions. Because of this mixing, alternating regions of high flow and low flow spaced at intervals of less than 0.5 cm are unlikely explanations for the curved semilog plots.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Radio frequency (13.56 MHz) energy enhances recovery from mild hypothermia.

The rate of warming after hypothermia depends on the method of rewarming. This study compared the effectiveness of radio frequency (RF) energy against hot (41 degrees C) water immersion (HW) and an insulated cocoon (IC) for rewarming hypothermic men. Six men fasted overnight and were rewarmed for 1 h after attaining a 0.5 degree C reduction in rectal temperature (Tre). Tre and esophageal (Tes) temperature were recorded every 5 min with nonmetallic thermal probes. The base-line value for Tre and Tes just before rewarming was subtracted from each 5 min Tre and Tes during rewarming to give delta Tre and delta Tes. The 12 delta Tes values were averaged for each individual and were compared using analysis of variance. The average delta Tes for RF (1.15 +/- 0.22 degrees C/h) was faster (P less than 0.001) than either IC (0.37 +/- 0.16 degrees C/h) or HW (0.18 +/- 0.09 degree C/h). The present study shows the superiority of RF energy for rewarming mildly hypothermic men.

Adult↗
PubMed1988

The modulation of oxygen toxicity by intermittent exposure.

Intermittent delivery of hyperbaric O2 protects animals from pulmonary and central nervous system toxicity: more total O2 time can be tolerated if interrupted by short periods of low O2. Little is known about the mechanisms or optimization of systematically varied intermittency. Survival time was recorded in groups of 16 awake guinea pigs (239 +/- 23(SD) g) exposed to continuous O2 at 2.8 ATA or to one of six different schedules of O2 delivered with periodic air (PO2 = 0.588 ATA) interruptions. The survival curves had a lag time (11-14 hr of O2 time depending on the intermittency schedule) with a rapid loss of animals thereafter. Data were analyzed with risk models linking the probability of death to the accumulation of a putative toxic substance, X1. A model in which X1 accumulated in proportion to the PO2 and disappeared by first-order decay during periods of low O2 exposure was modified to include an effective rate constant for changes in X1: dX1/dt = a.PO2 + K1.(PO2 - Os).X1. First-order kinetics operated when PO2 was below the oxygen set point (Os), but the rate constant reversed sign to become a self-amplifying system when PO2 was above Os. This model achieved an excellent fit as judged by goodness-of-fit statistics while a simpler one did not. Our analysis suggests that the accumulation of toxicity does not correspond to a stable linear toxic process, but requires one in which a toxic process grows autocatalytically.

Animals↗
PubMed1988

Effects of lipopolysaccharide, lipid A, lipid X, and phorbol ester on cultured bovine endothelial cells.

In pursuing the mechanism of endotoxin action, we examined the effect of lipopolysaccharide (LPS) and its chemically defined components, lipid A and lipid X on cultured bovine endothelial cells. We report that LPS and lipid A caused detachment and altered morphology of endothelial cells while lipid X did not. Phorbol myristate acetate, a compound known to activate protein kinase C, also caused endothelial cell detachment. Morphologic changes were readily apparent in the endothelial cells after 6 hours of exposure to lipopolysaccharide (1 microgram/ml); at that time many of the cells had contracted and formed bleblike structures on the surface. Large vacuoles, dense bodies, and pyknotic nuclei were found in the detaching cells, indicating necrosis or cell death. Preceding the morphologic changes and actual detachment, endothelial cell DNA and RNA synthesis was impaired by LPS. The changes in DNA and RNA synthesis occurred within 4 hours of exposure to 1 microgram/ml of LPS when the cells were still able to maintain normal levels of ATP. In addition to the inhibition of nucleic acid synthesis, protein synthesis was inhibited after 6 and 8 hours of LPS exposure. DNA, RNA, and protein synthesis returned to control levels after 24 hours of exposure. Investigation on the cultured bovine endothelial cells as a model for LPS action was useful in that these cells are sensitive to relatively low levels of LPS and the endothelium may be an important target in sepsis.

Animals↗
PubMed1987

Tracheal pressure and impedance as determinants of gas exchange during high frequency ventilation.

This work explores the use of catheter pressure transducers to measure time averaged, mean squared pressure (MSP) in the trachea of anesthetized animals during high frequency ventilation using a prototype Emerson oscillator with a 25 ml stroke volume at 15 and 34 Hz. Tidal volume and MSP were varied by shunting a portion of the ventilator output for the study of the effect of driving pressure on ventilation. A given level of ventilation was accomplished at a lower driving pressure at the lower frequency. Both ventilation as assessed by a modified nitrogen washout procedure and gas exchange were related to MSP and oscillatory frequency by the substitution of MSP/Z2 for alveolar ventilation in the equations of Jaeger et al. (1984). The technique and equations describing it were validated by the prediction of impedance changes resulting from shifts in oscillatory frequency. The calculated impedances matched experimentally measured values found in dogs by other investigators. Catheter pressure transducers are thus shown to be a useful tool for quantifying high frequency ventilation when coupled with a knowledge of respiratory impedance. The technique offers advantages over existing techniques, the most notable being ease of use due to the catheters' exceptional frequency response.

Animals↗
PubMed1987

Spare receptors, partial agonists, and ternary complex model of drug action.

The occurrence of spare receptors and partial agonists for smooth muscle contractions mediated by alpha 1-adrenergic receptors can be accounted for with a ternary complex model of drug action presented here. In this model, receptor-ligand complexes are assumed to be inactive until the complex binds to an activating protein. Contractile responses are assumed to be proportional to the concentration of ternary complex (receptor-ligand-activator) regardless of the ligand involved. Antagonists are unable to form the ternary complex. Spare receptors are present as the inactive receptor-ligand complex. Such a model is shown to fit already published data on membrane binding of alpha 1-adrenergic agonists as well as contractile responses to the agonist. Schild plots are expected to resemble those of a single-site model of drug action. The double-reciprocal plots of receptor-inactivation studies will display only a slight curvature as may be seen in previously published articles. Partial agonists may have 50% response doses lowe or higher than full agonists. The hypothesis that ternary complexes are formed with alpha 1-receptors could be tested more critically with receptor-inactivation studies using both antagonists and agonists. Partial inactivation of receptor and activator protein should reduce the binding of antagonist without altering the concentration needed to bind to 50% of the receptors. On the other hand, the concentration of agonist required to displace 50% of a bound antagonist is expected to increase. The proposal that contractile responses are proportional to the ternary complex concentration could be tested by fitting the ternary complex model to the data from studies of contractions induced by partial agonists as well as full agonists.

Adrenergic alpha-Agonists↗
PubMed1987

An analysis of decrements in vital capacity as an index of pulmonary oxygen toxicity.

Decrements in vital capacity (% delta VC) were proposed by the Pennsylvania group in the early 1970s as an index of O2-induced lung damage. These workers used the combined effects of PO2 and time of exposure to develop recommendations to limit expected % delta VC. Adopting this general approach, we fitted human pulmonary O2 toxicity data to the hyperbolic equation % delta VC = Bs.(PO2 - B1).(time)B3 using a nonlinear least squares analysis. In addition to the data considered in 1970, our analysis included new data available from the literature. The best fit was obtained when 1) an individual slope parameter, Bs, was estimated for each subject instead of an average slope; 2) PO2 asymptote B1 = 0.38 ATA; and 3) exponent B3 = 1.0. Wide individual variation imposed large uncertainty on any % delta VC prediction. A 12-h exposure to a PO2 of 1 ATA would be expected to yield a median VC decrement of 4%. The 80% confidence limits, however, included changes from +1.0 and -12% delta VC. Until an improved index of pulmonary O2 toxicity is developed, a simplified expression % delta VC = -0.011.(PO2 - 0.5).time (PO2 in ATA and time in min) can be used to predict a median response with little loss in predictability. The limitations of changes in VC as an index are discussed.

Humans↗
PubMed1986

How well mixed is inert gas in tissues?

The washout of inert gas from tissues typically follows multiexponential curves rather than monoexponential curves as would be expected from homogeneous, well-mixed compartment. This implies that the ratio for the square root of the variance of the distribution of transit times to the mean (relative dispersion) must be greater than 1. Among the possible explanations offered for multiexponential curves are heterogeneous capillary flow, uneven capillary spacing, and countercurrent exchange in small veins and arteries. By means of computer simulations of the random walk of gas molecules across capillary beds with parameters of skeletal muscle, we find that heterogeneity involving adjacent capillaries does not suffice to give a relative dispersion greater than one. Neither heterogeneous flow, nor variations in spacing, nor countercurrent exchange between capillaries can account for the multiexponential character of experimental tissue washout curves or the large relative dispersions that have been measured. Simple diffusion calculations are used to show that many gas molecules can wander up to several millimeters away from their entry point during an average transit through a tissue bed. Analytical calculations indicate that an inert gas molecule in an arterial vessel will usually make its first vascular exit from a vessel larger than 20 micron and will wander in and out of tissue and microvessels many times before finally returning to the central circulation. The final exit from tissue will nearly always be into a vessel larger than 20 micron. We propose the hypothesis that the multiexponential character of skeletal muscle tissue inert gas washout curves must be almost entirely due to heterogeneity between tissue regions separated by 3 mm or more, or to countercurrent exchanges in vessels larger than 20 micron diam.

Capillaries↗
PubMed1986

Nitrogen gas exchange in the human knee.

Human decompression sickness is presumed to result from excess inert gas in the body when ambient pressure is reduced. Although the most common symptom is pain in the skeletal joints, no direct study of nitrogen exchange in this region has been undertaken. For this study, nitrogen tagged with radioactive 13N was prepared in a linear accelerator. Nine human subjects rebreathed this gas from a closed circuit for 30 min, then completed a 40- to 100-min washout period breathing room air. The isotope 13N was monitored continuously in the subject's knee during the entire period using positron detectors. After correction for isotope decay (half-life = 9.96 min), the concentration in most knees continued to rise for at least 30 min into the washout period. Various causes of this unexpected result are discussed, the most likely of which is an extensive redistribution of gas within avascular knee tissues.

Half-Life↗
PubMed1985

Diminished pressor response to exogenous norepinephrine and angiotensin II in septic, unanesthetized rats: evidence for a prostaglandin-mediated effect.

Despite elevated plasma concentrations of norepinephrine (NE), septic patients generally have normal or low mean arterial pressure (MAP) and systemic vascular resistance. We tested the hypothesis that sustained sepsis in rats results in relative hyporesponsiveness to the pressor actions of NE and angiotensin II (AII). Sprague-Dawley rats were studied 48 hr after sepsis was induced by cecal ligation. Sham-operated rats served as controls. Carotid artery and jugular venous catheters were placed under halothane anesthesia and the rats were allowed to waken fully in restraining cages. Peak increments in MAP were measured after bolus iv doses of NE (0.125-8.0 micrograms/kg) or AII (0.0125-0.5 microgram/kg). Some rats were pretreated with indomethacin (5 mg/kg, iv) 30 min prior to the dose-response study. Data were fitted to a two-parameter hyperbolic function and the resulting curves were compared by analysis of variance. Compared with controls, sepsis decreased the pressor response to both NE (P less than 0.0001) and AII (P less than 0.0001). Indomethacin restored responsiveness toward normal for both pressor agents (P less than 0.0001). It is concluded that sepsis is associated with hyporesponsiveness to two chemically dissimilar vasopressors and that this phenomenon may be mediated by prostaglandins.

Analysis of Variance↗
PubMed1985

Decompression outcome following saturation dives with multiple inert gases in rats.

This investigation examined the question of whether gas mixtures containing multiple inert gases provide a decompression advantage over mixtures containing a single inert gas. Unanesthetized male albino rats, Rattus norvegicus, were subjected to 2-h simulated dives at depths ranging from 145 to 220 fsw. At pressure, the rats breathed various He-N2-Ar-O2 mixtures (79.1% inert gas-20.9% O2); they were then decompressed rapidly (within 10 s) to surface pressures. The probability of decompression sickness (DCS), measured either as severe bends symptoms or death, was related to the experimental variables in a Hill equation model incorporating parameters that account for differences in the potencies of the three gases and the weight of the animal. The relative potencies of the three gases, which affect the total dose of decompression stress, were determined as significantly different in the following ascending order of potency: He less than N2 less than Ar; some of these differences were small in magnitude. With mixtures, the degree of decompression stress diminished as either N2 or Ar was replaced by He. No obvious advantage or disadvantage of mixtures over the least potent pure inert gas (He) was evident, although limits to the expectation of possible advantage or disadvantage of mixtures were defined. Also, model analysis did not support the hypothesis that the outcome of decompression with multiple inert gases in rats under these experimental conditions can be explained totally by the volume of gas accumulated in the body during a dive.

Animals↗
PubMed1985

Statistical aspects of the design and testing of decompression tables.

Before a decompression procedure is recommended for general use it is subjected to a limited number of human trial dives. Based on the trial, one attempts to reject unsafe procedures but accept those with a low incidence of decompression sickness (DCS). Binomial confidence regions are often so broad that even after 40 dives it may be impossible to distinguish between the possibility that the table being tested has a 0.6% risk of DCS and the possibility that it has a 17% risk. Our proposed alternative is to select some rule (e.g., one or more cases of DCS in 10 dives) for rejecting tables and to calculate the probabilities of accepting tables as a function of the probability of DCS. With such calculations we conclude that (a) generally one cannot reduce the risk of adopting unsafe tables without increasing the risk of rejecting safe ones unless one chooses to increase the number of test dives; (b) truncated sequential designs could reduce the number of dives required for testing by 15 to 20%; and (c) rules similar to the ones tested will always have a zone of indifference. Tables with a probability of DCS in this zone will be accepted or rejected with nearly equal frequency even if tested with hundreds of dives. The use of models describing the probability of DCS as a function of dive parameters should allow us to combine information from dives previously analyzed separately and perhaps to improve our selection of new tables to be tested.

Atmospheric Pressure↗