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Biomedical subjects

J P Butler

Publications and source records attributed to J P Butler.

104 records · Page 6Linked to original sources

Pituitary luteinizing hormone responses to intravenous and subcutaneous administration of gonadotropin-releasing hormone in men.

Although differences in plasma GnRH concentrations have been identified after iv and sc injection of this peptide, differences in pituitary LH responses to iv and sc GnRH have not been evaluated in detail. We studied the magnitude and contour of plasma GnRH and LH responses after low doses of iv and sc GnRH administered to men with idiopathic hypogonadotropic hypogonadism and compared them to LH pulses in normal men after endogenous GnRH secretion. Mean areas under the LH response curves differed significantly (P less than 0.01) after 25 ng/kg, but not 250 ng/kg, iv and sc GnRH doses. The mean time from basal to peak plasma LH concentrations was significantly longer with sc than iv GnRH (P less than 0.02). In addition, individual LH responses were more variable with sc GnRH. Intravenous administration produced greater GnRH amplitude (P less than 0.001) and area under the curve (P less than 0.005) and shorter time to peak (P less than 0.01) GnRH concentrations. When plasma LH responses of similar area and amplitude were compared, the contour of LH responses after iv GnRH more closely simulated the LH pulses in normal men. These data demonstrate that 1) significant differences exist in the amplitude, contour, and variability of plasma LH and GnRH pulses after iv and sc GnRH; and 2) iv GnRH elicits LH secretory episodes which closely resemble endogenous pulsations of normal men. These results suggest that iv GnRH administration may be preferred in physiological studies and, if the data can be extrapolated to women, may account for the greater success of ovulation induction reported with iv GnRH.

Adolescent↗

Contribution of tree structures in the lung to lung elastic recoil.

The direct contribution of forces in tree structures in the lung to lung recoil pressure and changes in recoil pressure induced by alterations of the forces are analyzed. The analysis distinguishes the contributions of axial and circumferential tensions in the trees and indicates that only axial tensions directly contribute to static recoil. This contribution is derived from analysis of the axial forces transmitted across a random plane transecting the lung. The change in recoil pressure induced by changes in axial tension is similarly derived. Alterations of circumferential tensions in the trees indirectly change recoil by causing nonuniform deformations of the surrounding lung parenchyma, and a continuum elasticity solution for the stress induced by the deformations is derived. Sample calculations are presented for the airway tree based on available data on airway morphometric and mechanical properties. The increase in recoil pressure accompanying increases in axial and circumferential tensions with contraction of airway smooth muscle is also analyzed. The calculations indicate that axial stresses in the airway tree out to bronchioles directly contribute only a small fraction of the static recoil pressure. However, it is found that contraction of smooth muscle in these airways can increase recoil pressure appreciably (10-20%), mainly by the deformation of the parenchyma with increases in circumferential tension in smaller airways. The results indicate that the geometric and mechanical properties of the airway tree are such that only peripheral elements of the tree can substantially affect the elastic properties of the lung. The possible contributions of vascular trees for which data on mechanical and morphometric properties are more limited are also discussed.

Lung↗

Neuroendocrine regulation of the corpus luteum in the human. Evidence for pulsatile progesterone secretion.

The pattern of episodic gonadotropin release was studied in 15 normal female volunteers during the luteal phase of the menstrual cycle with 24 h of blood sampling for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels at 10-min intervals. Six subjects (two in the early, two in the mid-, and two in the late luteal phase) also had each of these specimens processed for progesterone levels. A progressive slowing of LH pulsations was present across the luteal phase with the mean LH pulse frequency declining from 15.2 pulses/24 h in the early to 8.4/24 h in the late luteal phase. A trend towards reduction in the amplitude of LH pulses was also observed (12.3 +/- 2.2 SD mIU/ml in the early vs. 8.6 +/- 3.4 mIU/ml in the late luteal phase; NS). In addition, LH pulses of heterogeneous amplitude were identified during the same 24-h study. The mean +/- SD of the larger and of the smaller LH pulses was 16.9 +/- 4.7 and 2.3 +/- 1.0 mIU/ml, respectively (P less than 0.001). While the slowing of the frequency of all LH pulses correlated well (r = 0.80, P less than 0.001) with the day of the luteal phase and poorly with the actual plasma progesterone levels, the incidence of the small LH pulses was highest in the mid-luteal phase and correlated well with the mean progesterone plasma levels (r = 0.63, P less than 0.01). In the early luteal phase, the pattern of progesterone secretion was stable over the 24-h studies and showed no relationship to episodic LH release. In contrast, in the mid- and late luteal phase, plasma progesterone concentrations rapidly fluctuated during the 24-h studies from levels as low as 2.3 to peaks of 40.1 ng/ml, often within the course of minutes. Progesterone increments closely attended episodes of LH release, as documented by the significant (P less than 0.05) cross-correlation between LH and progesterone levels, at time lags of 25-55 min. The results of this study indicate that in the human luteal phase: (a) the frequency of pulsatile release of LH declines progressively and correlates well with the duration of exposure to progressively and correlates well with the duration of exposure to progesterone; (b) the amplitude of LH pulses varies with the appearance of an increased percentage of smaller pulses correlating well with the acute level of progesterone; (c) in the early luteal phase, the pattern of progesterone secretion is stable; (d) in the mid- and late luteal phase, progesterone secretion is episodic, and correlates with LH pulsatile release; and (e) single progesterone estimations in the mid- and late luteal phase do not accurately reflect corpus luteum adequacy.

Corpus Luteum↗

Fast integrated flow plethysmograph for small mammals.

The accurate measurement of a forced vital capacity (FVC) maneuver in a small mammal requires that the plethysmograph in use have good response characteristics at high frequencies. We develop, on a theoretical basis, the behavior of zeroth-order (pressure type), first-order (flow type without inertance), and second-order (flow type with inertance) plethysmogrphs. The actual frequency response of a mouse-sized plethysmograph is then presented, and a technique for improving its response characteristics is described. A flat amplitude response (within 3% of a reference flow taken as truth) was obtained for sinusoidal inputs below 240 Hz. A phase lag with respect to the reference flow equivalent to a simple time delay of 1.4 ms was observed up to 150 Hz. A typical FVC curve for a mouse is shown, and criteria are provided for designing similar plethysmographs suitable for use with larger animals.

Animals↗

Lung recoil during rapid vital capacity expirations simulated by gas compression.

Excised dog lobes were inflated to a transpulmonary pressure (PL) of about 30 cmH2O, and their airways were occluded. Then they were rapidly compressed to a volume where PL was about zero, simulating forced expiratory maneuvers. Since there was no airflow during the compression, PL was a direct measure of lung recoil. Lung volume (VL) was calculated from absolute airway pressure using Boyle's law. At ambient temperature, lung recoil pressure during compressive maneuvers simulating forced vital capacity expirations (Pdyn) was less than that during quasi-static (30 s) compressions (Pst). Typically the dynamic component (i.e., Pst--Pdyn) decreased from about 2 cmH2O near total lung capacity to no difference at the end of the compression. Cooling the lobes to 15 degrees C increased Pst-Pdyn, and warming the lobes to 37 degrees C reduced Pst-Pdyn almost to zero. We suggest that the driving force of lung recoil during expirations is adequately modeled by the quasi-static VL/PL relationship, though a small correction should be made for excised lungs at room temperature.

Airway Resistance↗

Estimating a distribution's central moments: a specific tidal ventilation application.

A method is presented for extracting central moments of a distribution from data generated by the distribution over a known kernel. It is applied to the problem of the specific tidal ventilation in the lung in the multiple-breath N2-washout setting, and we found that in estimating the mean and variance, the method accurately recovers from test data those values characteristic of a test distribution. Some preliminary results on normal subjects are shown.

Humans↗

Indirect estimation of physiological distribution functions.

Multicompartment models, such as sums of exponential decays and sums of effects of different ventilation-perfusion ratios, are cast in the form of integrals. Difficulties in obtaining the density function in such an integral from measured values of the integral are attributed to amplification of error in the inversion solution and to the limited number of measurement points. The present approach to control the effect of the error is regularization with the use of a non-negativity constraint on the density function. The answers are sums of the influence or kernel functions of the integral wherever the sum is positive, and zero elsewhere. Such non-negative answers not only ensure that true density functions are obtained but also permit the answer to fall abruptly to zero. For example, a delta function can be much more closely approximated with the non-negativity constraint than without. A rule is developed to choose the value of smoothing parameter so as to minimize an approximate upper bound on the integral of the squared error of the answer. This typically tends to result in some oversmoothing. Functions tested without error and with 2% relative error are as follows: one of the kernel functions (best results); rectangular boxes and delta functions (fair results); and wide boxes (poor results).

Models, Biological↗

Airway geometry by analysis of acoustic pulse response measurements.

Serial distribution of airway properties determines in part the response of the lung to high frequency oscillations. We measured the response of excised dog lungs and lobes between 156 and 10,000 Hz and determined the area-distance function of the acoustically equivalent structure having rigid walls, regular branching, and negligible internal losses. The utility of this techique was tested by determining the effects of air trapping, removal of pleura from a dried lung, central airway smooth muscle tone. A strong correlation was found between relative changes in equivalent acoustic area and relative area changes measured radiographically in individual airways at corresponding distances. We conclude that despite departures of the properties of the real lung from the characteristics of the acoustically equivalent structure, changes in the area-distance function computed by this technique provide reasonable estimates of the magnitude and serial distribution of actual changes in airway cross-sectional area.

Acoustic Impedance Tests↗

A model for cytoplasmic rheology consistent with magnetic twisting cytometry.

Magnetic twisting cytometry is gaining wide applicability as a tool for the investigation of the rheological properties of cells and the mechanical properties of receptor-cytoskeletal interactions. Current technology involves the application and release of magnetically induced torques on small magnetic particles bound to or inside cells, with measurements of the resulting angular rotation of the particles. The properties of purely elastic or purely viscous materials can be determined by the angular strain and strain rate, respectively. However, the cytoskeleton and its linkage to cell surface receptors display elastic, viscous, and even plastic deformation, and the simultaneous characterization of these properties using only elastic or viscous models is internally inconsistent. Data interpretation is complicated by the fact that in current technology, the applied torques are not constant in time, but decrease as the particles rotate. This paper describes an internally consistent model consisting of a parallel viscoelastic element in series with a parallel viscoelastic element, and one approach to quantitative parameter evaluation. The unified model reproduces all essential features seen in data obtained from a wide variety of cell populations, and contains the pure elastic, viscoelastic, and viscous cases as subsets.

Animals↗