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Biomedical subjects

S R Thomas

Publications and source records attributed to S R Thomas.

At least 127 records · Page 7Linked to original sources

Electrophysiology of Necturus urinary bladder: II. Time-dependent current-voltage relations of the basolateral membranes.

As reported previously (S.R. Thomas et al., J. Membrane Biol. 73:157-175, 1983) the current-voltage (I-V) relations of the Na-entry step across the apical membrane of short-circuited Necturus urinary bladder in the presence of varying mucosal Na concentrations are (i) time-independent between 20-90 msec and (ii) conform to the Goldman-Hodgkin-Katz constant field flux equation for a single cation over a wide range of voltages. In contrast, the I-V relations of the basolateral membrane under these conditions are (i) essentially linear between the steady-state, short-circuited condition and the reversal potential (Es); and (ii) are decidedly time-dependent with Es increasing and the slope conductance, gs, decreasing between 20 and 90 msec after displacing the transepithelial electrical potential difference. Evidence is presented that this time-dependence cannot be attributed entirely to the electrical capacitance of the tissue. The values of gs determined at 20 msec are linear functions of the short-circuit current, Isc, confirming the relations reported previously, which were obtained using a more indirect approach. The values of Es determined at 20 msec are significantly lower than any reasonable estimate of the electromotive force for K across the basolateral membrane, indicating that this barrier possesses a significant conductance to other ions which may exceed that to K. In addition, these values increase linearly with decreasing Isc and approach the value of the electrical potential difference across the basolateral membrane observed when Na entry across the apical membrane is blocked with amiloride or when Na is removed from the mucosal solution. A possible explanation for the time-dependence of Es and gs is offered and the implications of these findings regarding the interpretation of previous microelectrophysiologic studies of epithelia are discussed.

Animals↗

An interactive 24-channel event-logging system based on the AIM 65 single-board microcomputer.

Measures of the spontaneous behaviour of animals commonly involve the repetitive counting of behavioural events over successive periods of time following some experimental treatment. An automated event-logging system has been designed for such applications. The system is based on an AIM 65 microcomputer with 4 Kbytes of random-access memory and facilities for manual event-logging through the keyboard, or automatic logging via a signal-conditioning buffer, connected to the backplane connector of the computer. The control program is written in 6500 machine code and stored in an onboard, read-only, memory chip. The software generates a simple interactive dialogue for the selection of operating options which include manual or automatic modes, configuration of active channels, duration and number of logging cycles, and the choice of printed or transmitted output. The microcomputer can also be instructed to pause and then to restart, to print out its current status, or to abort. The system has been used over a period of 18 months in numerous experiments in this laboratory, and has proved to be reliable, accurate and entirely suited to its application.

Animals↗

Practical aspects involved in the design and set up of a 0.15 T, 6-coil resistive magnet, whole body NMR imaging facility.

Many technical and logistical questions must be addressed when planning the installation of an NMR imaging system. These considerations become particularly significant when the facility is being established within an existing medical center complex. This paper presents a report on the practical aspects and experience obtained in siting a 6-coil 0.15 T resistive magnet system. The topics discussed include: floor loading; ferromagnetic environment; the effect of iron on the magnet field strength and homogeneity characteristics; shimming procedures; temperature stability requirements; rf shielding; and effects of the magnetic field on common medical instrumentation and magnetic media. It was found that the field shift as a function of the distance of a steel mass from the center of the magnet exhibited an (1/r)5.2 +/- 0.5 to (1/r) 4.2 +/- 0.3 dependence for axial and radial positions respectively which, as expected, is somewhat weaker than the (1/r)6 dependence expected by point dipole approximations. Field distortions caused by the presence of ferromagnetic material in radial positions may be essentially fully compensated with first order transverse shim coils (most conveniently, the x and y imaging gradient coils could be used). Axially distributed material requires, in addition to first order z-gradient correction, higher order axial shim compensation. The temperature stability of the magnet system over the scan period must be better than 0.2 degrees C to insure that temperature-induced field fluctuations are less than the intrinsic static inhomogeneity: and, ideally, below 0.01 degrees C to reduce these fluctuations to less than those caused by power supply instability.

Construction Materials↗

Venous uptake of 201T1 as thallous chloride.

Thallium-201, injected as thallous chloride, has been found to adhere to or be taken up by the vein into which it is injected, permitting images to be obtained of human veins up to 4 h following injection. A digoxin-insensitive rat vein model also retained 201Tl but for shorter periods of time. 201Tl uptake is independent of the solution into which it is introduced, whether 5% dextrose or 0.9% sodium chloride. This technique permits multiple delayed views of normal veins to be obtained but is of uncertain value in the evaluation of thrombophlebitis of the calf because of rather poor resolution and high cost.

Animals↗

[Transport of chlorine in the proximal tubule. Its effects on water-electrolyte absorption].

Several studies in rat kidney have established that an appreciable fraction of proximal absorption is passive in nature and occurs across the highly conductive paracellular pathway. Passive absorption is generally ascribed to the transepithelial Cl- distribution, luminal Cl- activity (alpha lCl) being higher than plasma Cl- activity (alpha pCl). The inequality alpha lCl greater than alpha pCl generates a transepithelial diffusion potential, lumen positive, which taken together with the chemical potential differences of Cl- and Na+ across the epithelium gives rise to transepithelial electrochemical potential differences for Cl- and Na+ favoring their absorption. The alpha lCl greater than alpha pCl distribution is traditionally ascribed to preferential bicarbonate absorption. We argue that HCO3- absorption alone cannot generate a non equilibrium transepithelial Cl- distribution. Other mechanisms are necessary. Our measurements in amphibian proximal tubule demonstrate that the intracellular Cl- activity, alpha cCl, is higher than the theoretical value predicted for equilibrium. This distribution is the result of two basolateral coupled transport processes (Cl-/HCO3- exchange and Cl-/Na+ cotransport). It contributes to the exit of Cl- from cell to lumen (by passive diffusion and K+/Cl- cotransport), yielding alpha lCl values higher than the theoretical value for equilibrium with regard to plasma. Thus, a small transcellular flux of Cl- (without solvent) proceeds from interstitium to lumen. It compensates the dissipative tendency of a much higher paracellular Cl- absorptive flux (in association with water) on the transepithelial Cl- gradient. The result is a steady-state luminal Cl- distribution above equilibrium, along the major part of the proximal tubule.

Animals↗

Relation between effective radiation dose and outcome of radioiodine therapy for thyroid cancer.

We used a combination of radioiodine scanning and quantitative radiation dosimetry to evaluate responses to therapeutic irradiation with 131I in 76 patients with thyroid adenocarcinoma. Fifty patients received 131I treatment for ablation of residual thyroid tissue after surgical thyroidectomy, and 26 had 131I treatment for metastatic thyroid cancer. Successful ablation was observed in patients receiving higher radiation doses to the thyroid--about 4.4 times those in patients whose lesions were not ablated--largely because of a longer effective half-life of 131I in residual thyroid tissue in the patients with ablated lesions. Patients with metastases that persisted after 131I therapy tended to have more advanced disease and received significantly lower radiation doses per millicurie of administered 131I than did persons whose lesions responded to treatment. Initial 131I treatment resulting in radiation doses of at least 30,000 rad to thyroid remnants and 8000 rad to metastases was associated with a significant increase in the rate of response to therapy.

Adenocarcinoma↗

Low iodine diet in I-131 ablation of thyroid remnants.

A low-iodine diet was developed for used in decreasing iodine intake and excretion in patients undergoing evaluation with radioactive I-131 for ablation of thyroid remnants as treatment for thyroid cancer. It has been demonstrated to effectively lower iodine excretion to less than 25% of basal values. Preliminary calculations suggest that such iodine depletion may be potentially useful in increasing the radiation dose per mCi of administered activity in I-131 ablative therapy.

Adenocarcinoma↗

Radiation absorbed-dose estimates for the liver, spleen, and metaphyseal growth complexes in children undergoing gallium-67 citrate scanning.

Quantitative conjugate-view external counting techniques were applied to estimate the radiation dose to the liver, spleen, and metaphyseal growth complexes (distal femur and proximal tibia) for ten pediatric patients undergoing gallium-67 scanning procedures. The effective half-life of Ga 67 in these organs was approximately 78 hours. The dose per unit of administered activity for the liver and spleen was between 0.3 and 4.0 rad/mCi (0.08 to 1.08 Gy/GBq) and 0.5 and 7.0 rad/mCi (0.13 to 1.89 Gy/GBq), respectively. For the metaphyseal growth plates, the range was 2.3 to 14.3 rad/mCi (0.62 to 3.86 Gy/GBq).

Adolescent↗

Characteristics of extrafocal radiation and its potential significance in pediatric radiology.

Extrafocal radiation was investigated using four different rotating-anode radiographic units currently employed in a pediatric hospital. It was found to exhibit significant penetration, with an effective energy only slightly lower than that of the primary radiation. The percentage of extrafocal relative to focal radiation in pediatric procedures involving rare-earth screens ranged from 2 to 15%. The ratio of extrafocal to focal radiation tended to increase with increasing kVp, mA, and field size but was independent of focal spot size. Since extrafocal radiation may extend significantly outside of the primary collimated field, radiosensitive organs such as the gonads, thyroid, and eyes which are assumed to be shielded may actually receive as much as 25 mR per radiograph.

Child↗

Stimulation of dome formation in MDCK kidney epithelial cultures by inducers of differentiation: dissociation from effects on transepithelial resistance and cyclic AMP levels.

Changes in transepithelial electrical resistance and cyclic nucleotide levels were monitored accompanying chemical induction of domes in a clonal subline of MDCK kidney epithelial cells. Confluent cell monolayers grown on nitrocellulose filters exhibited a relatively high mean transepithelial resistance (387 ohms X cm2). Hexamethylene bisacetamide, a potent inducer of dome formation (Lever, 1979b), stimulated significantly increased transmonolayer resistance as well as elevated levels of intracellular cyclic AMP. By contrast, dimethylformamide, an equally potent inducer of dome formation in MDCK cells, did not appreciably alter either resistance values or cyclic nucleotide levels. These results suggest that induction of dome formation in epithelial cell cultures by compounds generally known as inducers of differentiation may involve multiple and separate mechanisms.

Acetamides↗

Nuclear magnetic resonance imaging techniques as developed modestly within a university medical center environment: what can the small system contribute at this point?

This paper describes a geometrically small NMR imaging system which has been developed and assembled within a university medical center environment. Consideration is given to the technical specifications and basic economics for the magnet system, NMR spectrometer, and computer configuration. Initial research objectives for the system are outlined which include (1) the signal-to-noise improvement potential of rotational gradient imaging, and (2) 19F tracer imaging considerations with a detailed discussion concerning the feasibility of in vivo NMR imaging of 19F-fluorodeoxyglucose (2-FDG and 3-FDG). Finally, potentially significant areas for research within the constraints of a small NMR imaging system are described.

Academic Medical Centers↗

A network thermodynamic model of glomerular dynamics: application in the rat.

A model of glomerular dynamics has been developed by using network thermodynamics and the SPICE 2 computer program to further explore the determinants of glomerular filtration. The model is designed to be holistic and self-adjusting, taking cognizance of and permitting quantitation of the secondary alterations in individual effective glomerular resistances, glomerular blood and plasma flow, capillary oncotic pressure and glomerular capillary pressure, which inevitably result when any parameter affecting glomerular dynamics changes. Such automatic adjustment adds to the precision of computation and is unique to the present model. Few assumptions are introduced, independent variables (arterial pressure, individual resistances, hydraulic conductivity, hematocrit, and serum protein concentration) being entered whereas values for the dependent variables are determined by the computer. In rats, filtration pressure equilibrium is seen not to obtain either under physiologic conditions or with reasonably large changes in any of the independent variables. Capillary pressure is shown to be affected by any maneuver that modulates single nephron GFR (SNGFR) and flow across the efferent arteriole (for example, tubule pressure, serum protein concentration) even when arteriolar caliber is held constant. The axial rise in colloid oncotic pressure and serum protein concentration along the capillary is found to be neither linear nor semilogarithmic, a characteristic that reflects on equations used to determine capillary hydraulic conductivity. Isolated change in afferent arteriolar resistance is shown by the model to produce a linear relationship between glomerular plasma flow and capillary pressure, and thus between the former parameter and filtration. Large solitary increases in efferent arteriolar resistance raise SNGFR and a 60% fall in resistance virtually abolishes filtration while exerting little change in blood flow. Concomitant and equal alterations of afferent and efferent arteriolar resistances cause filtration to rise linearly with blood flow but to produce minor change in glomerular capillary pressure, an example of true plasma flow dependence. Plasma flow dependence is, however, found to be unique to this particular circumstance under physiologic conditions. Adding an optional element that automatically adjusts effective efferent arteriolar resistance as a function of Hct2 has but modest effects on glomerular dynamics except when systemic hematocrit is substantially altered. The data and conclusions derived in this study are based on typical values for resistances, hydraulic conductivity, systemic protein concentration, hematocrit, and arterial and tubular pressures reported for normal hydropenic rats. They will not necessarily hold in other species in which these values may be distinctly different.

Animals↗