Effect of expiratory resistive loading on the noninvasive tension-time index in COPD.

Expiratory resistive loading (ERL) is used by chronic obstructive pulmonary disease (COPD) patients to improve respiratory function. We, therefore, used a noninvasive tension-time index of the inspiratory muscles (TT(mus) = I/PI(max) x TI/TT, where I is mean inspiratory pressure estimated from the mouth occlusion pressure, PI(max) is maximal inspiratory pressure, TI is inspiratory time, and TT is total respiratory cycle time) to better define the effect of ERL on COPD patients. To accomplish this, we measured airway pressures, mouth occlusion pressure, respiratory cycle flow rates, and functional residual capacity (FRC) in 14 COPD patients and 10 normal subjects with and without the application of ERL. TT(mus) was then calculated and found to drop in both COPD and normal subjects (P<0.05). The decline in TT(mus) in both groups resulted solely from a prolongation of expiratory time with ERL (P<0.001 for COPD, P<0.05 for normal subjects). In contrast to the COPD patients, normal subjects had an elevation in I and FRC, thus minimizing the decline in TT(mus). In conclusion, ERL reduces the potential for inspiratory muscle fatigue in COPD by reducing TI/TT without affecting FRC and I.     

Noninvasive measurement of bone mineral mass in the unanesthetized rabbit.

Direct photon absorptiometry was used for the in vivo measurement of bone mineral mass in the rabbit tibia. Bone mineral mass in 124 male and female rabbits was correlated (p less than 0.001) with age to 26 weeks and weight to 5.5 kg. Examining reproducibility and repositioning error, three rabbits were measured 12 times each. Bone mineral mass in the three rabbits was: 0.432 +/- 0.020 g/cm2, 0.414 +/- 0.010 g/cm2 and 0.487 +/- 0.037 g/cm2. The greatest coefficients of variance observed for measurements without repositioning and measurements with repositioning were 4.8% and 7.6%, respectively. The technique provided sensitive, reproducible and noninvasive measurement of bone mineral mass without anesthesia or undue restraint.     

Noninvasive measurement of midexpiratory flow indicates bronchoconstriction in allergic rats.

This study was designed to evaluate the value and applicability of tidal breathing pattern analysis to assess bronchoconstriction in conscious rats. Using noninvasive, head-out body plethysmography and the decrease in tidal midexpiratory flow (EF(50)), we measured airway responsiveness (AR) to inhaled acetylcholine and allergen in conscious Brown-Norway rats, followed by invasive determination of pulmonary conductance (GL) and EF(50) in anesthetized rats. Dose-response studies to acetylcholine showed that noninvasively recorded EF(50) closely reflected the dose-dependent decreases observed with the invasive monitoring of simultaneously measured GL and EF(50). After sensitization and intratracheal boost to ovalbumin or saline, rats were assessed for early and late AR to aerosolized ovalbumin. Ovalbumin aerosol challenge resulted in early and late AR in allergen-sensitized rats, whereas controls were unresponsive. The allergen-specific AR, as measured noninvasively by EF(50), was similar in degree compared with invasively recorded EF(50) and GL and was associated with enhanced IgE and airway inflammation. We conclude that EF(50) is a noninvasive and physiologically valid index of bronchoconstriction in a rat model of asthma.     

Noninvasive cardiac output measurement in orthostasis: pulse contour analysis compared with acetylene rebreathing.

We tested the reliability of noninvasive cardiac output (CO) measurement in different body positions by pulse contour analysis (CO(pc)) by using a transmission line model (K. H. Wesseling, B. De Wit, J. A. P. Weber, and N. T. Smith. Adv. Cardiol. Phys. 5, Suppl. II: 16-52, 1983). Acetylene rebreathing (CO(rebr)) was used as a reference method. Twelve subjects (age 21-34 yr) were studied: 1) six in whom CO(rebr) and CO(pc) were measured in the standing and 6 degrees head-down tilt (HDT) postures and 2) six in whom CO was measured in the 30 degrees HDT, supine, 30 degrees head up-tilt (HUT), and 70 degrees HUT postures on a tilt table. The CO(rebr)-to-CO(pc) ratio in (near) the supine position during rebreathing was used as the calibration factor for CO(pc) measurements. Calibrated CO(pc) (CO(cal sup)) consistently overestimated CO in the upright posture. The drop in CO with upright posture was underestimated by approximately 50%. CO(cal sup) and CO(rebr) values did not differ in the 30 degrees HDT position. Changes in the CO(rebr)-to-CO(pc) ratio are highly variable among subjects in response to a change in posture. Therefore, CO(pc) must be recalibrated for each subject in each posture.     

Noninvasive measurement of dissolved oxygen in shake flasks

Shake flasks are ubiquitous in cell culture and fermentation. However, conventional devices for measuring oxygen concentrations are impractical in these systems. Thus, there is no definitive information on the oxygen supply of growing cells. Here we report the noninvasive, nonintrusive monitoring of dissolved oxygen (DO) in shake flasks using a low-cost optical sensor. The oxygen-sensitive element is a thin, luminescent patch affixed to the inside bottom of the flask. The sensitivity and accuracy of this device is maximal up to 60% DO, within the range that is critical to cell culture applications. By measuring actual oxygen levels every 1 or 5 min throughout the course of yeast and E. coli fermentations, we found that a modest increase in shaker speed and a decrease in culture volume slowed the onset of oxygen limitation and reduced its duration. This is the first time that in situ oxygen limitation is reported in shake flasks. The same data is unattainable with a Clark type electrode because the presence of the intrusive probe itself changes the actual conditions. Available fiber optic oxygen sensors require cumbersome external connections and recalibration when autoclaved.     

Noninvasive ultrasonic measurement of arterial wall motion in mice

Despite the extensive use of genetically altered mice to study cardiovascular physiology and pathology, it remains difficult to quantify arterial function noninvasively in vivo. We have developed a noninvasive Doppler method for quantifying vessel wall motion in anesthetized mice. A 20-MHz probe was held by an alligator clip and positioned over the carotid arteries of 16 mice, including six 3- to 5-mo-old wild-type (WT), four 30-mo-old senescent (old), two apolipoprotein E null (ApoE), and four alpha-smooth muscle actin null (alpha-SMA) mice. Doppler signals were obtained simultaneously from both vessel walls and from blood flow. The calculated displacement signals from the near and far walls were subtracted to generate a diameter signal from which the excursion and an augmentation index were calculated. The excursion ranged between 13 microm (in ApoE) and 95 microm (in alpha-SMA). The augmentation index was lowest in the WT mice (0.06) and highest in the old mice (0.29). We conclude that Doppler signal processing may be used to measure vessel wall motion in mice with high spatial and temporal resolution and that diameter signals can replace pressure signals for calculating the augmentation index. This noninvasive method is able to identify and confirm characteristic changes in arterial properties previously associated with age, atherosclerosis, and the absence of vascular tone.     

Noninvasive determination of exercise-induced hydrodgen ion threshold through direct optical measurement.

The intensity of exercise above which oxygen uptake (Vo2) does not account for all of the required energy to perform work has been associated with lactate accumulation in the blood (lactate threshold, LT) and elevated carbon dioxide output (gas exchange threshold). An increase in hydrogen ion concentration ([H+]) is approximately concurrent with elevation of blood lactate and CO2 output during exercise. Near-infrared spectra (NIRS) and invasive interstitial fluid pH (pHm) were measured in the flexor digitorum profundus during handgrip exercise to produce a mathematical model relating the two measures with an estimated error of 0.035 pH units. This NIRS pHm model was subsequently applied to spectra collected from the vastus lateralis of 10 subjects performing an incremental-intensity cycle protocol. Muscle oxygen saturation (SmO2) was also calculated from spectra. We hypothesized that a H+ threshold could be identified for these subjects and that it would be different from but correlated with the LT. Lactate, gas exchange, SmO2, and H+ thresholds were determined as a function of Vo2 using bilinear regression. LT was significantly different from both the gas exchange threshold (Delta = 0.27 +/- 0.29 l/min) and H+ threshold (Delta = 0.29 +/- 0.23 l/min), but the gas exchange threshold was not significantly different from the H+ threshold (Delta = 0.00 +/- 0.38 l/min). The H+ threshold was strongly correlated with LT (R2 = 0.95) and the gas exchange threshold (R2 = 0.85). This initial study demonstrates the feasibility of noninvasive pHm estimations, the determination of H+ threshold, and the relationship between H+ and classical metabolic thresholds during incremental exercise.     

Intestinal permeability in children with Crohn's disease and coeliac disease.

Mannitol and lactulose were used as probe molecules to measure intestinal permeability in children with active small-bowel Crohn''s disease and with untreated coeliac disease. Mannitol and lactulose were administered by mouth in a moderately hypertonic solution (580 mmol (mosmol)/l), and results were expressed as the ratio of the molecules excreted in urine over five hours. Patients with Crohn''s disease had a sixfold increase in permeability (due to increased lactulose permeability) and those with coeliac disease a fivefold increase (due to decreased mannitol permeability). From these results the test offers potential as a noninvasive investigation in children with small-bowel disease.     

Noninvasive measurement of mucosal immunity in a free-ranging baboon population

Ecoimmunological patterns and processes remain understudied in wild primates, in part because of the lack of noninvasive methods to measure immunity. Secretory immunoglobulin A (sIgA) is the most abundant antibody present at mammalian mucosal surfaces and provides an important first line of defense against pathogens. Recent studies show that sIgA can be measured noninvasively in feces and is a good marker of mucosal immunity. Here we validated a commercial ELISA kit to measure fecal IgA in baboons, tested the robustness of its results to variation in collection and storage conditions, and developed a cost-effective in-house ELISA for baboon fecal IgA. Using data from the custom ELISA, we assessed the relationship between fecal IgA concentrations and gastrointestinal parasite burden, and tested how sex, age, and reproductive effort predict fecal IgA in wild baboons. We find that IgA concentrations can be measured in baboon feces using an in-house ELISA and are highly correlated to the values obtained with a commercial kit. Fecal IgA concentrations are stable when extracts are stored for up to 22 months at −20°C. Fecal IgA concentrations were negatively correlated with parasite egg counts (Trichuris trichiura), but not parasite richness. Fecal IgA did not vary between the sexes, but for males, concentrations were higher in adults versus adolescents. Lactating females had significantly lower fecal IgA than pregnant females, but neither pregnant nor lactating female concentrations differed significantly from cycling females. Males who engaged in more mate-guarding exhibited similar IgA concentrations to those who engaged in little mate-guarding. These patterns may reflect the low energetic costs of mucosal immunity, or the complex dependence of IgA excretion on individual condition. Adding a noninvasive measure of mucosal immunity will promote a better understanding of how ecology modulates possible tradeoffs between the immune system and other energetically costly processes in the wild.