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Biomedical subjects

E Kimmel

Publications and source records attributed to E Kimmel.

At least 19 recordsLinked to original sources

Ultrasound-facilitated transport of silver chloride (AgCl) particles in fish skin.

Electron-dense nano-particles in aqueous suspension were administered by immersion into the epidermis of fish using ultrasound in the therapeutic range. Enhanced permeability of the tissues to the particles was achieved by acoustic cavitation, which induced a controlled level of necrosis in the outer cell layers, and by non-cavitational exposures, which widened intercellular spaces of non-necrosed tissue in deeper regions of the epidermis. Both particle concentration and penetration depth were quantified using transmission electron microscopy. While cavitation-induced perforation was necessary for particles to penetrate into the tissues, non-cavitational exposures during immersions increased the particle flux towards the skin surface, as well as the diffusion rate of the particles within the epidermis and their depth of penetration. The technique described above may potentially be applied for non-stressful, mass-administration of substances into aquatic animals, as well as the relatively new field of ultrasound-facilitated delivery in moist epithelial tissues in humans.

Animals↗

Ultrasound-induced intercellular space widening in fish epidermis.

Transmission electron microscopy was employed to determine the effects of therapeutic ultrasound (US) (I(sata) < or =2.2 W cm(-2), 3 MHz), sonicated at different angles and durations, on the external epithelia of fish skin. Sonication at 1.7 W cm(-2) (90 s), where the ultrasonic beam was perpendicular to the skin surface, produced minor intercellular space widening (ICSW), as well as the disruption of desmosomes connecting between the cells. Increasing the intensity to 2.2 W cm(-2) increased ICSW, the extent of which was positively correlated to the duration of exposure (30 to 90 s). Perpendicular sonication produced ICSW, almost exclusively between cells of the two outermost cell layers, parallel to the skin surface. Sonicating at 45 degrees (2.2 W cm(-2), 90 s) produced ICSW in deeper cell layers in the tissues, in which the spaces were at seemingly random orientations. Mucous cells and macrophages were also found to be damaged, as were apoptotic epidermal cells. The suggested mechanism for ICSW is the formation of transverse (shear) waves at the interface between the aquatic medium and the skin surface. The waves, which are damped out within a few cell layers, give rise to shear stresses that, in turn, cause strains that act to separate between cells and damage some of the relatively weaker cells.

Animals↗

Ultrasound-induced cavitation damage to external epithelia of fish skin.

Transmission electron microscopy was used to show the effects of therapeutic ultrasound (< or = 1.0 W/cm2, 1 MHz) on the external epithelia of fish skin. Exposures of up to 90 s produced damage to 5 to 6 of the outermost layers. Negligible temperature elevations and lack of damage observed when using degassed water indicated that the effects were due to cavitation. The minimal intensity was determined for inducing cellular damage, where the extent and depth of damage to the tissues was correlated to the exposure duration. The results may be interpreted as a damage front, advancing slowly from the outer cells inward, presumably in association with the slow replacement of the perforated cell contents with the surrounding water. This study illustrates that a controlled level of microdamage may be induced to the outer layers of the tissues.

Animals↗

Collagen arrangement in hepatic granuloma in mice infected with Schistosoma mansoni: dependence on fiber radiation centers.

The collagen structure of isolated and in situ liver granuloma from Swiss Webster mice infected with Schistosoma mansoni was sequentially and three-dimensionally analyzed during different times of infection (early acute, acute, transitional acute-chronic, and chronic phases) by laser scanning confocal microscopy and electron scanning variable vacuum microscopy. The initial granuloma structure is characterized by vascular collagen residues and by anchorage points (or fiber radiation centers), from where collagenous fibers are angularly shed and self-assembled. During the exudative-productive stage, the self-assembly of these fibers minimizes energy and mass through continuous tension and focal compression. The curvature or angles between collagen fibers probably depends on the fibroblastic or myofibroblastic organization of stress fibers. Gradually, the loose unstable lattice of the exudative-productive stage transforms into a highly packed and stable architecture as a result of progressive compactness. The three-dimensional architecture of granulomas provides increased tissue integrity, efficient distribution of soluble compounds and a haptotactic background to the cells.

Animals↗

Histoarchitecture of schistosomal granuloma development and involution: morphogenetic and biomechanical approaches.

The authors present morphogenetic and biomechanical approaches on the concept of the Schistosoma mansoni granulomas, considering them as organoid structures that depend on cellular adhesion and sorting, forming rearrangement into hierarchical concentric layers, creating tension-dependent structures, aiming to acquire round form, since this is the minimal energy form, in which opposing forces pull in equally from all directions and are in balance. From the morphogenetic point of view, the granulomas function as little organs, presenting maturative and involutional stages in their development with final disappearance (pre-granulomatous stages, subdivided in: weakly and/or initial reactive and exudative; granulomatous stages: exudative-productive, productive and involutional). A model for the development of granulomas was suggested, according to the following stages: encapsulating, focal histolysis, fiber production, orientation and compacting and involution and disintegration. The authors concluded that schistosomal granuloma is not a tangled web of individual cells and fibers, but an organized structure composed by host and parasite components, which is not formed to attack the miracidia, but functions as an hybrid interface between two different phylogenetic beings.

Animals↗

Lung tissue resistance and hysteretic moduli of lung parenchyma.

Lung tissue resistance (Rti) represents a large and labile component of total pulmonary resistance, but the mechanism is unknown. One hypothesis that has received some support in the literature is that on exposure to contractile agonists airway smooth muscle shortens and then, by the agency of elastic interdependence, induces distortion in surrounding parenchyma. Parenchymal distortion induced in the vicinity of a constricted airway is a pure shear deformation, but currently there are no data available for shear hysteresivity. Guided by a microstructural model, we have assigned stiffness and hysteresivity to microstructural elements and then computed how those properties are expressed at the macroscale in bulk hysteresivities for both shear and volumetric expansion. Hysteresivity for volumetric expansion is shown to be a stiffness-weighted average of hysteresivities of all microstructural components. But as the hysteresivity of microstructural elements increases, that for shear deformation increases to some degree but eventually attains a plateau. Blunted hysteretic response in shear seems to be an intrinsic property of pressure-supported structures, like the lung, that require an inflating pressure to ensure mechanical stability. The analysis indicates that that part of Rti attributable to parenchymal distortion can be at most a small fraction of that attributable to volumetric expansion. These results are purely theoretical in nature, and this suggests that caution is necessary in their interpretation. However, the mechanical basis of the results is sufficiently general to conclude that the hypothesis that parenchymal distortion secondary to bronchoconstriction can account for Rti and its changes seems to be implausible.

Airway Resistance↗

The steady expiratory pressure-flow relation in a model pulmonary bifurcation.

Experiments were conducted over a range of Reynolds numbers from 50 to 8000 to study the pressure-flow relationship for a single bifurcation in a multi-generation model during steady expiratory flow. Using the energy equation, the measured static pressure drop was decomposed into separate components due to fluid acceleration and viscous energy dissipation. The frictional pressure drop was found to closely approximate that for an equivalent length of curved tube with the same curvature ratio as in the model bifurcation. The sensitivity of these results to changes in airway cross-sectional shape, non-planar configuration, and flow regime (laminar-turbulent) was investigated. In separate experiments using dye visualization and hot-wire anemometry, a transition to turbulent flow was observed at Reynolds numbers between 1000 and 1500. Transition had very little effect on the pressure-flow relation.

Acceleration↗

Numerical schemes for unsteady fluid flow through collapsible tubes.

The study of fluid flow through compliant tubes is a fluid-structure type problem, in which a dynamic equilibrium is maintained between the fluid and the tube wall. The analogy between this flow and gas dynamics initiated the use of a number of numerical methods which were originally developed to solve compressible flow in rigid ducts. In this study we investigate the solutions obtained by applying the Lax-Wendroff and MacCormack schemes to one-dimensional incompressible flow through a straight collapsible tube. The time-evolving numerical results were compared with exact steady-state solutions. For boundary conditions which were held fixed after a prescribed rise time, the unsteady numerical solution converges to the exact steady-state solution with very good accuracy. The stability and accuracy of all the methods depend on the amount of viscous pressure loss dictated by wall friction. Flows with undamped oscillations cannot, however, be solved with these techniques.

Elasticity↗

Determination of the toxicity of cyclotriphosphazene hydraulic fluid by 21-day repeated inhalation and dermal exposure.

Cyclotriphosphazene (CTP) ester is one of a series of compounds developed for use as a fire-resistant hydraulic fluid. The most significant routes of industrial exposure to hydraulic fluids are dermal, because of spills or leaks, and aerosol inhalation from pressurized system leaks. This study was designed to evaluate the toxic effects associated with repeated or continuous exposure to CTP by both dermal and inhalation routes. Male and female Fischer 344 (F-344) rats were exposed for 3 weeks to air alone, or to 0.25, 0.50, or 1.00 mg CTP/L. No deaths or signs of toxic stress occurred during the exposure period. A depression in mean body weight gain and increases in numbers of pulmonary alveolar macrophages and renal hyaline droplets were noted in both genders. Male and female New Zealand White (NZW) rabbits were treated dermally for 3 weeks with mineral oil, or 0.25, 0.50, or 1.00 g CTP/kg. No toxic effects were noted in either gender of rabbits.

Administration, Cutaneous↗

Surface tension and the dodecahedron model for lung elasticity.

Macroscopic elastic moduli governing the incremental deformations of lung parenchyma are calculated on the basis of a model for an individual lung element in the shape of a regular dodecahedron. Elastic stiffness within the element is provided by pin-jointed tension members along the edges of the dodecahedron, surface tension is incorporated into its pentagonal faces, and the influence of transpulmonary pressure is simulated by an externally applied hydrostatic tension. The analysis is based on a variational statement of nonlinear structural mechanics, and the results show how the moduli depend on the effective inflation pressure, the constitutive behavior of the idealized truss members, and the surface-area dependent surface tension. The theory is discussed in the light of available experimental information. A more general analysis is needed to account for the effects of structural as well as surface-tension hysteresis.

Elasticity↗

Numerical solutions for steady and unsteady flow in a model of the pulmonary airways.

A computational model is presented for unsteady flow through a collapsible tube with variable wall stiffness. The one-dimensional flow equations are solved for inlet, outlet and external conditions that vary with time and for a tube with time-dependent, spatially-distributed local properties. In particular, the effects of nonuniformities and local perturbations in stiffness distribution in the tube are studied. By allowing the flow to evolve in time, asymptotically steady flows are calculated. When simulating a quasi-steady reduction in downstream pressure, the model demonstrates critical transitions, the phenomena of wave-speed limitation and the sites of flow limitation. It also exhibits conditions for which viscous flow limitation occurs. Computations of rapid, unsteady changes of the exit pressure illustrate the phenomena occurring at the onset of a cough, and the generation and propagation of elastic jumps.

Computer Simulation↗

A cellular model of lung elasticity.

The mechanics of the lung parenchyma is studied using models comprised of line members interconnected to form 3-D cellular structures. The mechanical properties are represented as elastic constants of a continuum. These are determined by perturbing each individual cell from a reference state by an increment in stress which is superimposed upon the uniform stretching forces initially present in the members due to the transpulmonary pressure. A force balance on the distorted structure, together with a force-deformation law for the members, leads to a calculation of the strain increments of the members. Predictions based on the analysis of the 3-D isotropic dodecahedron are in good agreement with experimental values for the Young's, shear, and bulk moduli reported in the literature. The model provides an explanation for the dependence of the elastic moduli on transpulmonary pressure, the geometrical details of the structure, and the stress-strain law of the tissue.

Elasticity↗

Augmentation of cardiac output and carotid blood flow by chest and abdomen phased compression cardiopulmonary resuscitation.

Phased compression cardiopulmonary resuscitation, whereby the chest and abdomen are compressed sequentially, is a new approach to the classical cardiopulmonary resuscitation technique, which is based on the compression of the chest alone. Six dogs with cardiac arrest were treated by external chest and abdominal compression using a rigid plexiglas suit lined with flexible perithoracic and periabdominal bladders. Fast inflation and deflation of the two independent bladders, together with forced ventilation of the lung, generated phased pressure pulses. The physiological variables monitored throughout the experiment included central venous, left ventricular, and central arterial pressures, carotid blood flow, cardiac output, and acid base balance. The phased compression technique was performed with phased time lags of 0, 150, 300, 400, 600, 700, and 850 ms between the abdominal and thoracic pressure pulses. A random sequence of the different phased compression modes, each lasting for 3-10 minutes, was applied during the prolonged resuscitation procedure that lasted for up to 70 minutes. By starting the abdominal compression 300-400 ms before the thoracic compression the carotid flow index improved by 77% (from 13% with simultaneous compression to 23% with phased compression) and the cardiac output index increased by 65% (from 7.8% with simultaneous compression to 12.5%). The results provide insight into the chest pump concept and the role of intrathoracic and intra-abdominal pressures in generating improved blood circulation during cardiopulmonary resuscitation, and show the advantages of phased compression over chest compression alone and simultaneous chest and abdominal compression.

Animals↗

Morphologic and physiologic response of lungs to steroid and cigarette smoke: an animal model.

The combined effects of cigarette smoke inhalation and hydrocortisone acetate (HCA) treatment induce prominent abnormalities in lungs of C57BL/6 male mice. These abnormalities include (1) a marked reduction of pulmonary macrophage population which is normally elevated by smoke inhalation, (2) an accumulation of surfactant and flocculent material in alveoli, (3) a decrease in alveolar space surrounded by normal septal tissue, and (4) an increase in hypertrophied alveolar parenchyma. Concomitant with altered lung morphology, lung volume and gas diffusing capacity were significantly compromised in animals subjected to smoke exposure and steroid treatment. It was found that smoke inhalation or HCA administration alone had no ill effects on the animals. The data presented indicate that manifestation of pathologic conditions resembling pulmonary fibrosis and pulmonary alveolar proteinosis is a result of cigarette smoke-drug interaction. The information reported provides a basis for an animal model which might be applicable to assessment of factors related to smoke inhalation and development of pulmonary disorders.

Animals↗

Intrathoracic and abdominal pressure variations as an efficient method for cardiopulmonary resuscitation: studies in dogs compared with computer model results.

Intrathoracic pressure variations are currently proposed as the main flow-generation mechanisms in standard and modified cardiopulmonary resuscitation (CPR) techniques. A method of changing pressure within the thorax and abdomen without any degree of heart compression was developed and tested in dogs. Intrathoracic and abdominal pressure waves were induced by cyclic inflation and deflation of the lungs and of perithoracic and periabdominal balloons. Various modes of CPR, depending on the rate of cycling, the use of a periabdominal balloon inflation, and a delay between the abdominal and thoracic pressure waves, were studied during ventricular fibrillation. During artificial systole (high intrathoracic pressure phase), the pressure which developed in the right ventricle (96.7 +/- 20.5 mmHg) was higher than the pressure in the aorta (89.3 +/- 20.5 mmHg, p less than 0.001). In artificial diastole (low intrathoracic pressure phase), the right ventricular pressure (11.7 +/- 2.6 mmHg) was lower than the aortic pressure (17.5 +/- 3.3 mmHg, p less than 0.001). The average flow in the carotid artery was 21.7 +/- 7.8 ml . min-1, which was 18 +/- 6% of the baseline carotid flow before CPR. Three different factors were found to improve the efficiency of CPR: periabdominal balloon inflation simultaneous with the intrathoracic pressure waves; increased frequency of the pressure waves from 60 to 100 cycles per minute; and inflation of the periabdominal balloon 50 to 100 ms before the thoracic balloon. Blood-gas and acid-base balance analysis during CPR revealed well-oxygenated arterial blood with a marked respiratory alkalosis and a slowly developing metabolic acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗

[Spondyloepiphyseal dysplasia tarda].

The authors report on a case of spondyloepiphyseal dysplasia tarda (SDT). The most important clinical and radiological signs are described and the criteria for differential diagnosis listed. Among the bone dysplasias Maroteaux, Lamy and Bernhard distinguished in 1957 a discrete form which they called spondyloepiphyseal dysplasia tarda. The condition was found in 20 patients from four generations of three families studied. SDT is a rare and little-known abnormality of bone development. There have been very few communications concerning this condition. Furthermore, this very rare condition is not considered often enough in differential diagnosis and the findings are often misinterpreted; this also occurred in earlier examinations of the case reported here. As early as 1937, Volhard et al. saw a clinical picture corresponding to this condition in three brothers, but they did not take the malformation to be an autonomous disease; they merely stated that the clinical picture differed from that of Morquio's disease. Giedeon et al. classified the changes found in their patients as being associated with Morquio-Brailsford dysostosis.

Adult↗

Pulsatile flow in tapered tubes: a model of blood flow with large disturbances.

Blood flow-through segments of large arteries of man, between adjacent bifurcations, can be modeled as pulsatile flow in tapered converging tubes, of small angle of convergence, up to 2 deg. Assuming linearity, rigid tube and homogeneous Newtonian fluid, the physiological flow field is governed by the Navier-Stokes equation with dominant nonlinear and unsteady terms. Analytical solution of this problem is presented based on an integral method technique. The solution shows that even for small tapering the flow pattern is markedly different from the flow obtained for a uniform tube. The periodic shear stresses at the wall and pressure gradients increase both in their mean value and amplitude with increased distance downstream. These results are highly significant in the process of atherogenesis.

Animals↗