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Biomedical subjects

J P Butler

Publications and source records attributed to J P Butler.

At least 55 records · Page 3Linked to original sources

Contour of the GnRH pulse independently modulates gonadotropin secretion in the human male.

GnRH pulse frequency, amplitude, and interpulse interval have all been demonstrated to regulate gonadotropin secretion individually. We tested the hypothesis that the contour of the GnRH pulse also modulates gonadotropin output in 10 men with isolated GnRH deficiency in whom a fixed GnRH dose was administered at a constant physiologic frequency by either instantaneous bolus or by 1-, 5-, or 30-min infusions. LH, FSH and free alpha subunit (FAS) responses were also compared to spontaneous gonadotropin secretion in normal adult men. While the LH and FAS pulses following the instantaneous bolus and 1-min infusion of GnRH were indistinguishable, further increases in the duration of gonadotrope stimulation by GnRH were associated with progressive decreases in all parameters of gonadotropin secretion (mean levels, amplitude, peak levels, AUC). FSH secretion was also decreased following variations in the contour of the GnRH pulse, although overall changes were less dramatic than for LH and FAS. The LH pulses following the bolus GnRH stimulation were indistinguishable from spontaneous LH pulses occurring in normal men whereas those stimulated by the 1-, 5-, and 30-min infusions of GnRH became progressively blunted with the lowest levels of secretion occurring after the longest infusion. In sharp contrast, FAS pulse parameters in the GnRH-deficient subjects greatly exceeded those of normal men regardless of the contour of the GnRH stimulus, whereas mean FSH levels were all modestly (although significantly) higher than those of normal adult men. These results demonstrate that the pituitary is sensitive to subtle changes in the contour of the GnRH stimulus, with a more prolonged duration of GnRH stimulation resulting in a diminished pituitary response. Alterations of the contour of endogenous GnRH secretion may represent an additional mechanism for altering gonadotrope function and provide additional evidence for the differential regulation of LH, FAS, and FSH by GnRH. However, the previously reported elevated levels of FAS secretion in GnRH-deficient men undergoing long-term GnRH replacement are not explained by abnormalities of GnRH contour.

Adult↗

Control of cell volume in oocytes and eggs from Xenopus laevis.

The mechanism by which Xenopus laevis oocytes and eggs survive in hypotonic media was investigated by measuring cell volume (Vc) and intracellular pressure (P(ic)) during osmotic swelling. After 2 hr in 10 mOsm buffer, eggs remained intact, while 60.2 +/- 7.0% of oocytes had burst. Water uptake was proportional to buffer osmolarity in oocytes, but not in eggs. We did not see a regulatory volume decrease in the cells, nor was there any evidence for osmolyte efflux. Oocyte P(ic) increased from 0.27 cm H2O (range 0.14-0.61 cm H2O) to 5.92 cm H2O (range 2.52-7.18 cm H2O, P < 0.001) after 70 min in 20 mOsm buffer. Egg P(ic) in 20 mOsm buffer (0.04 cm H2O, range -0.07 to 0.014 cm H2O) was not significantly different from the value in isotonic (200 mOsm) buffer (0.14 cm H2O, range 0-0.16 cm H2O). The data indicate that Vc in oocytes and eggs is not regulated by either plasma membrane ion transport or the mechanical properties of the vitelline envelope. While oocytes appear to behave as passive osmometers, we speculate that the ability of eggs to maintain volume is determined, in part, by the cytoplasm, in particular by its gel-like nature.

Animals↗

An intermeniscal fibrous band in a recreational runner.

An intermeniscal fibrous band was found to produce anterior knee pain in a recreational runner. Arthroscopic resection of the band eliminated the symptoms of pain with running. A literature review found no prior reports of this entity. The differential of plica syndrome and Hoffa's disease was reviewed.

Adipose Tissue↗

Model for a pump that drives circulation of pleural fluid.

Physical and mathematical models were used to study a mechanism that could maintain the layer of pleural fluid that covers the surface of the lung. The pleural space was modeled as a thin layer of viscous fluid lying between a membrane carrying tension (T), representing the lung, and a rigid wall, representing the chest wall. Flow of the fluid was driven by sliding between the membrane and wall. The physical model consisted of a cylindrical balloon with strings stretched along its surface. When the balloon was inflated inside a vertical circular cylinder containing a viscous fluid, the strings formed narrow vertical channels between broad regions in which the balloon pressed against the outer cylinder. The channels simulated the pleural space in the regions of lobar margins. Oscillatory rotation of the outer cylinder maintained a lubricating layer of fluid between the balloon and the cylinder. The thickness of the fluid layer (h), measured by fluorescence videomicroscopy, was larger for larger fluid viscosity (mu), larger sliding velocity (U), and smaller pressure difference (delta P) between the layer and the channel. A mathematical model of the flow in a horizontal section was analyzed, and numerical solutions were obtained for parameter values of mu, U, delta P, and T that matched those of the physical model. The computed results agreed reasonably well with the experimental results. Scaling laws yield the prediction that h is approximately (T/delta P)(microU/T)2/3. For physiological values of the parameters, the predicted value of h is approximately 10(-3) cm, in good agreement with the observed thickness of the pleural space.

Body Fluids↗

Chaotic mixing of alveolated duct flow in rhythmically expanding pulmonary acinus.

We examined the effects of rhythmic expansion of alveolar walls on fluid mechanics in the pulmonary acinus. We generated a realistic geometric model of an alveolated duct that expanded and contracted in a geometrically similar fashion to simulate tidal breathing. Time-dependent volumetric flow was generated by adjusting the proximal and distal boundary conditions. The low Reynolds number velocity field was solved numerically over the physiological range. We found that for a given geometry, the ratio of the alveolar flow (QA) to the ductal flow (QD) played a major role in determining the flow pattern. For larger QA/QD (as in the distal region in the acinus), the flow in the alveolus was largely radial. For small QA/QD (as in the proximal region in the acinus), the flow in the alveolus was slowly rotating and the velocity field near the alveolar opening was complex with a stagnation saddle point typical of chaotic flow structures. Performing Lagrangian fluid particle tracking, we demonstrated that in such a flow structure the motion of fluid could be highly complex, irreversible, and unpredictable even though it was governed by simple deterministic equations. These are the characteristics of chaotic flow behavior. We conclude that because of the unique geometry of alveolated duct and its time-dependent motion associated with tidal breathing, chaotic flow and chaotic mixing can occur in the lung periphery. Based on these novel observations, we suggest a new approach for studying acinar fluid mechanics and aerosol kinetics.

Airway Resistance↗

Assessment of patellar height after autogenous patellar tendon anterior cruciate ligament reconstruction.

In this study, we sought to determine if a significant change in patellar height occurs after autogenous patellar tendon anterior cruciate ligament (ACL) reconstruction at our clinic. In a series of 71 patients (52 males and 18 females; average age: 22 years; range: 12 to 41) randomly selected, all had undergone an identical autogenous patellar tendon ACL reconstruction, by the same surgeon, and followed the same postoperative accelerated rehabilitation program. All patients had standardized preoperative and postoperative lateral knee radiographs. The patellar tendon length as well as the patellar height and ratio of Blackburne and Peel were measured by the same person for all subjects. The length of the patellar tendon shortened by an average of 0.4 mm (range: 6% lengthening to 12% shortening) which is less than 1% and not statistically significant (P = .068). The Blackburne and Peel ratio for patellar height decreased by 1%, which was also not statistically significant (P = .060). The evidence obtained from this study indicated no significant change in patellar height after autogenous patellar tendon ACL reconstruction combined with postoperative accelerated rehabilitation and no correlations with postoperative complications, secondary surgeries, timing of surgery, age, or anterior knee symptoms.

Adolescent↗

Comparison of four methods for cross-calibrating dual-energy X-ray absorptiometers to eliminate systematic errors when upgrading equipment.

Dual-energy x-ray absorptiometry (DXA) is a widely employed technique for making noninvasive measurements of bone mineral density (BMD). Advances in DXA technology have resulted in the development of new densitometers that offer increased scan speed, improved spatial resolution, and the ability to make measurements at additional skeletal sites. However, changing from a first to a second-generation DXA system generates two additional potential sources of error. First, if the densitometers produce results that are substantially different, diagnostic errors occur if the results from both instruments are compared to the same normative database. Second, even if the densitometers produce results that are nearly identical, small systematic errors may influence interpretation of serial bone density measurements in individual patients. To assess the impact of changing from a first- to a second-generation DXA scanner, we made measurements using the standard "pencil beam" mode on 133 consecutive patients using both a Hologic QDR-1000 and a QDR-2000 densitometer when the latter instrument was calibrated according to the manufacturer's routine procedure using a single anthropomorphic spine phantom. We then recalculated the results for the QDR-2000 densitometer using cross-calibration factors based on (1) a regression line generated by scanning three anthropomorphic spine phantoms whose BMD ranged from osteoporotic to high normal on each instrument, (2) an adult human lumbar spine embedded in tissue-equivalent plastic, or (3) a regression line derived from scans of the first 83 patients that was then applied to the last 50 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

Semi-automated measurement of true chord length distributions and moments by video microscopy and image analysis.

The distribution of the lengths of airspace chords in pulmonary parenchyma characterizes many architectural features of the alveoli and alveolar ducts. Laborious to obtain manually, the distributions and density functions may be acquired semi-automatically by video microscopy, digitization and image processing. The accuracy of the estimation is influenced by the microscopical methods and also by the techniques used (i) to convert the digitized greyscale picture to a two-valued image, (ii) to collect the chord lengths and (iii) to compensate for finite field widths. The last problem arises because some chords are completely visible within a field while others are only partially seen, since one of the two air-tissue boundaries lies outside the field of view. This error systematically biases the observed distribution. This paper contains solutions to hardware, software and analytic problems encountered while developing the capability to measure airspace chord length density functions semi-automatically. Formulas for estimating the true chord length density function from samples of observed chord lengths are presented. Also given are formulas for the estimation of the first and second moments of the true chord length distribution from the means of observed chord lengths. These techniques of image preparation and analysis should be suitable for characterizing particle, grain or cell size distributions, especially where many profiles fall partially outside the field of view.

Animals↗

Noninvasive measurement of left ventricular myocardial elasticity.

We examined Advani and Lee's equation (ALeq) and a dimension analysis-derived equation (DAeq), both of which treat vibration of the elastic spherical shell and are able to estimate elasticity of the shell noninvasively when the sizes and eigen-frequency are provided. We confirmed that ALeq was numerically identical to DAeq and that both equations gave the precise elasticity of the silicone shell. Then we estimated left ventricular (LV) myocardial elasticity noninvasively at the moment of the first heart sound emission (1HS) in 25 healthy subjects and 14 hypertrophic cardiomyopathy (HCM) patients, based on the LV eigen-frequency detected by an intraesophageal miniature vibration sensor. HCM patients had a higher mean value of LV myocardial elasticity at 1HS than healthy subjects [102.3 +/- 33.4 vs. 70.7 +/- 24.4 kPa, P < 0.01 (Pa = N/m2 = 10 dyn/cm2)]. We thereby demonstrated the possibility of a noninvasive estimate of myocardial elasticity.

Adult↗

Effects of alveolated duct structure on aerosol kinetics. I. Diffusional deposition in the absence of gravity.

We examined the effects of alveolar duct structure on particle deposition in the pulmonary acinus. The low Reynolds number velocity field of carrier gas in a geometric model of the alveolated duct was solved numerically. Particle trajectories were computed from the Langevin equation. Conditional probabilities of the trajectories were calculated with an eigenfunction expansion technique in the absence of gravity. For submicron particles, Brownian motion dominated the process; the deposition rate dramatically decreased with boundary layer growth. For fine particles, fully developed boundary layer profiles determined the deposition over most of the acinar length. The assumption of a uniform radial profile results in a substantial overestimation of the local deposition rate. The deposition rate in an alveolated duct was always smaller than that in an equivalent straight tube of the same volume. Within the alveolus the deposition pattern was markedly nonuniform, with higher deposition near the alveolar entrance ring; this finding is consistent with experimental observations in animals (e.g., see Zeltner et al. J. Appl. Physiol. 70: 1137-1145, 1991). We conclude that the structure of the alveolar duct has an important influence on aerosol particle deposition in the lung acinus.

Aerosols↗

Effects of alveolated duct structure on aerosol kinetics. II. Gravitational sedimentation and inertial impaction.

We studied the effects of alveolated duct structure on deposition processes for particle diameters > or = 1 micron. For such large particles, Brownian motion is insignificant but gravity and inertial forces play an important role. A Lagrangian description of particle dynamics in an alveolated duct flow was developed, and computational analysis was performed over the physiologically relevant range. At low flow rates gravity caused deposition. Gravitational cross-streamline motion depended on the coupled effects of curvature of gas streamlines and duct orientation relative to gravity. The detailed convective flow pattern was an important factor in determining deposition. At higher flow rates, inertial impaction contributed markedly to deposition. The curved nature of streamlines again played a major role on deposition, but duct orientation had little effect. In the medium range of flow rates, both gravitational and inertial forces simultaneously influenced particle motion. Particle inertia, per se, did not cause deposition but substantially suppressed gravitational deposition. The deposition mechanism was complex; contrary to what is often assumed in past analyses, the interaction between gravitational and inertial effects could not be described in a simple additive fashion. We conclude that the structure of the alveolar duct has an important role in gravitational sedimentation and inertial impaction in the lung acinus.

Aerosols↗

A comparison of lateral versus anterior-posterior spine dual energy x-ray absorptiometry for the diagnosis of osteopenia.

Because bone mineral density (BMD) measurements at various sites differ in the relative amounts of cortical and trabecular bone that they assess, they also differ in their sensitivity for detecting osteopenia. Lateral spine dual energy x-ray absorptiometry (DXA) allows measurement of BMD of the vertebral bodies, which contain mainly trabecular bone, without contribution from the posterior vertebral elements, which are rich in cortical bone. Thus, we hypothesized that lateral spine DXA would detect osteopenia more frequently than anterior-posterior (AP) spine DXA. To assess the ability of DXA to estimate trabecular bone mass, we compared AP and lateral DXA spine measurements with trabecular bone measurements by quantitative computed tomography (QCT) in 58 patients. We then compared AP vs. lateral spine DXA measurements in 1) 300 women referred for routine bone densitometry, 2) 30 glucocorticoid-treated women, and 3) 44 women with vertebral compression fractures. To compare short term reproducibility, we performed repeat AP and lateral DXA scans in 50 women. The association between QCT and DXA measurements was stronger when DXA measurements were made in the lateral (r = 0.784) or midlateral (r = 0.823) projection than in the AP (r = 0.571) projection. The association of BMD with age was stronger when DXA measurements were made in the lateral (r = 0.536) or midlateral (r = 0.536) projection than in the AP (r = 0.382) projection. The declines in BMD with age for AP, lateral, and midlateral DXA measurements were 0.48%, 0.60%, and 0.88%/yr, respectively. In the women referred for routine densitometry, lateral DXA measurements were significantly (P < 0.05) more abnormal than AP measurements compared with those in young women. This was also true in the women treated with glucocorticoids and women with vertebral compression fractures. Lateral DXA often detected osteopenia in patients whose AP DXA was normal. The 95% confidence limits for changes in BMD attributable to measurement error for AP, lateral, and midlateral DXA were 0.027, 0.038, and 0.057 g/cm2, respectively. These results indicate that lateral DXA measurements identify patients with osteopenia more often than AP DXA measurements, probably because lateral DXA more accurately estimates trabecular bone mass. Short term reproducibility of lateral DXA is nearly as good as that for AP DXA.

Absorptiometry, Photon↗

Mechanical connections between elastin and collagen.

The ligament supporting the leading edge of birds' wings is a connective tissue structure with unusual morphologic and elastic features. Its center section is made of a highly extensible composite of elastin and collagen fibers and its two end sections of nearly inextensible pure collagen; these are joined end-to-end in short interdigitating junctions. Substantial forces are transmitted through the junctions showing that collagen and elastin are mechanically connected. The junctions and elastic segment are sufficiently strong that when the intact ligament is maximally strained, the point of failure is commonly in the collagenous segments or their attachments to the tissues of origin or insertion. Here we outline the morphology and describe static force-length properties of this ligament.

Animals↗

Mechanotransduction across the cell surface and through the cytoskeleton.

Mechanical stresses were applied directly to cell surface receptors with a magnetic twisting device. The extracellular matrix receptor, integrin beta 1, induced focal adhesion formation and supported a force-dependent stiffening response, whereas nonadhesion receptors did not. The cytoskeletal stiffness (ratio of stress to strain) increased in direct proportion to the applied stress and required intact microtubules and intermediate filaments as well as microfilaments. Tensegrity models that incorporate mechanically interdependent struts and strings that reorient globally in response to a localized stress mimicked this response. These results suggest that integrins act as mechanoreceptors and transmit mechanical signals to the cytoskeleton. Mechanotransduction, in turn, may be mediated simultaneously at multiple locations inside the cell through force-induced rearrangements within a tensionally integrated cytoskeleton.

Actin Cytoskeleton↗

Assessment of carcinogenic risk from personal exposure to benzo(a)pyrene in the Total Human Environmental Exposure Study (THEES).

The Total Human Environmental Exposure Study (THEES) was an investigation of multimedia exposure to the ubiquitous environmental carcinogen, benzo(a)pyrene (BaP). The three-phase study was conducted in Phillipsburg, New Jersey and involved the participation of 14-15 individuals (8-10 homes) during each 14-day monitoring period. Microenvironmental sampling of air, food, water and soil indicated that environmental exposure to BaP was primarily through air and food. Exposure and risk estimates were, therefore, based on the results of personal monitoring of breathing zone air and prepared food samples. Based on a comparison of the range and magnitude of inhalation and dietary BaP exposures, food ingestion was clearly the predominant exposure to pathway. The relative contributions of other potential sources of community exposure to BaP (e.g., soil and drinking water ingestion) were also assessed. The excess cancer risk estimates for food ingestion were consistently greater than those for personal air, reflecting both the predominantly higher BaP exposures through the diet and the higher carcinogenic potency value for oral exposure. Overall, the total lifetime risk from personal exposure to BaP for nonsmokers in the community was estimated at 10(-5). In identifying risk reduction options, it is important to account for the observation that personal activities, lifestyle, and diet strongly influenced individual exposures to BaP.

Air Pollutants↗

Geometric hysteresis in pulmonary surface-to-volume ratio during tidal breathing.

We investigated the dynamic history dependence of lung surface area-to-volume ratio (S/V) during tidal breathing in live rabbits with use of our recently developed technique of diffuse optical scattering. We also examined the effect of methacholine (continuous intravenous infusion, 1-10 micrograms.kg-1.min-1) on lung micromechanics with the same technique. Animals were anesthetized, tracheostomized, and mechanically ventilated, and the left lung was exposed through a thoracotomy. An optical fiber delivering light from a He-Ne laser was attached normal to the pleural surface, producing a circular light pattern on the pleural surface from diffusively scattered light within the parenchyma. The pattern of light intensities was measured using a CCD video camera connected to a computer. S/V during tidal breathing changed in a manner qualitatively consistent with geometric similarity. There was a small but significant hysteresis in S/V vs. volume, with S/V inspiration greater than S/V expiration at the same volume. However, during methacholine challenge, the sense of hysteresis reversed; S/V inspiration was less than S/V expiration at isovolume points. Moreover, S/V during methacholine challenge systematically decreased at all lung volumes compared with control. These findings suggest that 1) during normal tidal breathing, stress hysteresis in ductal tissue is larger than septal stress hysteresis (septal tissue plus surface tension) and 2) the effect of methacholine on tissue in the septa is greater than the corresponding effect in ductal tissue.

Animals↗

Mechanical independence of wingbeat and breathing in starlings.

The pectoral muscles in birds comprise up to a third of the body weight and provide the principal drive to the wing. Their attachment to the sternum suggests that they could compress the thorax and assist ventilation during flight. Most, but not all, birds have an integer ratio relationship between wingbeat and breathing frequency, but no measurements of the respiratory flow associated with the act of wingbeat are available. We recorded respiratory flow and wing timing in three starlings that flew at 22 knots (11 m.s-1) for up to 5 min in a wind tunnel. Triggering on wingbeat, we ensemble averaged flow records for many wingbeats in each flight. Because wingbeats occurred throughout the respiratory cycle, breathing flow tended to average to zero, and a small flow event related to wingbeat emerged. The volume change associated with wingbeat ranged from 3 to 11% of tidal volume, and this is probably an overestimate. We conclude that wingbeat and breathing in starlings are essentially mechanically independent, despite the direct attachment of the locomotor muscles to the thorax.

Animals↗

Effects of mechanical vibration on left ventricular diastolic properties during global ischemia.

To examine the effect of mechanical vibration on ventricular relaxation and diastolic chamber stiffness under global ischemia, we studied eight coronary perfused, isolated, isovolumic canine left ventricles (LV). To produce varying degrees of impaired relaxation, graded coronary flow reduction and paced tachycardia were imposed. A mechanical 50-Hz, 2-mm-amplitude vibration was applied during diastole and was turned off during systole. Without diastolic vibration, the relaxation time constant of LV pressure (tau) increased with the severity of ischemia. The chamber stiffness index (K) from the diastolic pressure-volume relationship showed a slight increase during ischemia; tau decreased with diastolic vibration. The change in tau with vibration increased with ischemia and was dependent on vibration amplitude but not heart rate. The ratio of tau to the diastolic interval (DI, the time from peak negative rate of LV pressure change to end diastole) always decreased with vibration and was linearly correlated with K (r = 0.93; P less than 0.01). K decreased with vibration when tau/DI was greater than 0.3. We conclude that diastolic vibration improves impaired relaxation and chamber stiffness under myocardial ischemia.

Analysis of Variance↗