Evaluation of a forced oscillation method to measure thoracic gas volume

The purposeof this study was to test a plethysmographic method of measuringthoracic gas volume (TGV) that, contrary to the usual panting method,would not require any active cooperation from the subject. It is basedon the assumption that the out-of-phase component of airway impedancevaries linearly with frequency. By using that assumption, TGV may becomputed by combining measurements of total respiratory impedance (Zrs)and of the relationship between the plethysmographic signal (Vpl) andairway flow () during forcedoscillations at several frequencies. Zrs and Vpl/were measured at 10 noninteger multiple frequencies ranging from 4 to29 Hz in 15 subjects breathing gas in nearlyBTPS conditions. Forced oscillationmeasurements were immediately followed by determination of TGV by thestandard method. The data were analyzed on different frequency ranges,and the best agreement was seen in the 6- to 29-Hz range. Within thatrange, forced oscillation TGV and standard TGV differed little(3.92 ± 0.66 vs. 3.83 ± 0.73 liters,n = 77, P < 0.05) and were stronglycorrelated (r = 0.875); thedifferences were not correlated to the mean of the two estimates, andtheir SD was 0.35 liter. In seven subjects the differences weresignificantly different from zero, which may, in part, be due toimperfect gas conditioning. We conclude that the method is not highlyaccurate but could prove useful when, for lack of sufficientcooperation, the panting method cannot be used. The results of computersimulation, however, suggest that the method would be unreliable in thepresence of severe airway inhomogeneity or peripheral airwayobstruction.

     

对胸腹部膨胀体积法测量小鼠潮气量可行性的评价

目的：探讨利用双体描箱法对胸腹部膨胀体积测量小鼠潮气量的可行性。方法：选用6只呼吸频率在90～120h／min的小鼠,通过双体描箱法进行潮气量和胸腹部膨胀体积的同步测量。结果：小鼠胸腹部膨胀体积为（0.369±0.014）ml,潮气量为（0.356±0.012）ml,前者显著高于后者（P〈0.01）。结论：目前常用的以胸腹部膨胀体积代替潮气量的测量方法不能准确测定潮气量。     

Measurement of thoracic gas volume by low-frequency ambient pressure changes

When the whole body is exposed to sinusoidal variations of ambient pressure (delta Pam) at very low frequencies (f), the resulting compression and expansion of alveolar gas is almost entirely achieved by gas flow through the airways (Vaw). As a consequence thoracic gas volume (TGV) may be computed from the imaginary part (Im) of the delta Pam/Vaw relationship: TGV = PB/[2 pi f X Im(delta Pam/Vaw)], where PB is barometric minus alveolar water vapor pressure. The method was tested in 35 normal subjects and compared with body plethysmography. The subjects sat in a chamber connected to a large-stroke-volume reciprocating pump that brought about pressure swings of 40 cmH2O at 0.05 Hz. delta Pam and Vaw were digitally processed by fast Fourier transform to extract the low-frequency component from the much larger respiratory flow. Total lung capacities (TLC) obtained by ambient pressure changes and by plethylsmography were highly correlated (r = 0.959, p less than 0.001) and not significantly different (6.96 +/- 1.38 l vs. 6.99 +/- 1.38). TLC obtained by ambient pressure changes were not influenced by lowering the frequency to 0.03 Hz, adding an external resistance at the mouth, or increasing abdominal gas volume. We conclude that the method is practical and in agreement with body plethysmography in normal subjects.     

Plethysmographic estimation of thoracic gas volume in apneic mice.

Electrical stimulation of intercostal muscles was employed to measure thoracic gas volume (TGV) during airway occlusion in the absence of respiratory effort at different levels of lung inflation. In 15 tracheostomized and mechanically ventilated CBA/Ca mice, the value of TGV obtained from the spontaneous breathing effort available in the early phase of the experiments (TGVsp) was compared with those resulting from muscle stimulation (TGVst) at transrespiratory pressures of 0, 10, and 20 cmH2O. A very strong correlation (r2= 0.97) was found, although with a systematically (approximately 16%) higher estimation of TGVst relative to TGVsp, attributable to the different durations of the stimulated (approximately 50 ms) and spontaneous (approximately 200 ms) contractions. Measurements of TGVst before and after injections of 0.2, 0.4, and 0.6 ml of nitrogen into the lungs in six mice resulted in good agreement between the change in TGVst and the injected volume (r2= 0.98). In four mice, TGVsp and TGVst were compared at end expiration with air or a helium-oxygen mixture to confirm the validity of isothermal compression in the alveolar gas. The TGVst values measured at zero transrespiratory pressure in all CBA/Ca mice [0.29 +/- 0.05 (SD) ml] and in C57BL/6 (N = 6; 0.34 +/- 0.08 ml) and BALB/c (N = 6; 0.28 +/- 0.06 ml) mice were in agreement with functional residual capacity values from previous studies in which different techniques were used. This method is particularly useful when TGV is to be determined in the absence of breathing activity, when it must be known at any level of lung inflation or under non-steady-state conditions, such as during pharmaceutical interventions.     

Evaluation of the measurement of B protein of plasma low density lipoprotein by radial immunodiffusion

Radial immunodiffusion (RID) has been used for determination of low density lipoprotein (LDL) B protein in plasma. During measurement of B protein in plasma and the d less than and d greater than 1.019 g/ml plasma fractions by RID in 1.0%, 1.5%, 2.0%, and 2.5% agarose, the d less than 1.019 g/ml lipoproteins diffuse in the agarose and produce precipitin rings. Among normotriglyceridemic subjects, the B protein values in whole plasma obtained by RID using 1.5 to 2.5% agarose were only slightly higher than the values in the d greater than 1.019 g/ml fraction obtained by RID and closely approximated the values obtained in the d greater than 1.019 g/ml fraction by radioimmunoassay. However, among the hypertriglyceridemic subjects, the RID measurement of B protein in plasma using 1.0 to 2.5% agarose overestimated the LDL B protein levels in plasma. The RID procedure at agarose concentrations of 1.5% to 2.5% can be used to estimate plasma LDL B protein levels in normotriglyceridemic subjects. However, measurement of LDL B protein by RID in plasma of hypertriglyceridemic subjects must be interpreted with caution; the LDL B protein is overestimated by this procedure because of the contribution by the d less than 1.019 g/ml lipoproteins to the B protein value.     

Evaluation of voiding dysfunction and measurement of bladder volume

When evaluating patients with voiding dysfunction, noninvasive tests such as uroflowmetry and measurement of postvoid residual urine volume (PVR) can help to determine whether additional testing is warranted. PVR can be measured by 2 methods: catheterization or bedside bladder ultrasonography. Although both methods have advantages, the convenience, efficiency, and safety of bladder ultrasound makes its use beneficial in a wide variety of populations, including hospitalized patients, children, and the elderly. More recently, bladder ultrasound has been used for other procedures, such as suprapubic aspiration, evaluation of intravesical masses, and to determine bladder wall thickness and bladder wall mass, both of which have been associated with outflow obstruction.     

Comparison of plethysmographic methods for obtaining thoracic gas volume in anesthetized dogs

In dogs, respiratory system resistance (Rrs) is frequency independent, and during high-frequency oscillatory ventilation (HFO) the relationship between CO2 elimination (VCO2) and frequency is linear. In contrast, we found in rabbits a large frequency-dependent decrease in Rrs with increasing frequency along with a nonlinear relationship between frequency and VCO2 (J. Appl. Physiol. 57: 354-359, 1984). We proposed that frequency dependent mechanical properties of the lung account for inter-species differences in the frequency dependence of gas exchange during HFO. In the current study we tested this hypothesis further by measuring VCO2 and Rrs as a function of frequency in a species of monkey (Macaca radiata). In these monkeys, Rrs decreased minimally between 4 and 8 Hz and in general increased at higher frequencies, whereas VCO2 was linearly related to frequency. This is further evidence supporting the hypothesis that nonlinear frequency-VCO2 behavior during HFO is related to frequency-dependent behavior in Rrs.     

Provision of cholesterol to lymphocytes by high density and low density lipoproteins. Requirement for low density lipoprotein receptors

The capacity of lipoprotein fractions to provide cholesterol necessary for human lymphocyte proliferation was examined. When endogenous synthesis of cholesterol was blocked, proliferation of mitogen-stimulated normal human lymphocytes was markedly inhibited unless an exogenous source of sterol was supplied. All lipoprotein fractions with the exception of high density lipoprotein subclass 3 were able to provide cholesterol for lymphocyte proliferation. Each of the lipoprotein subfractions capable of providing cholesterol was also able to regulate endogenous sterol synthesis in cultured human lymphocytes. Provision of cholesterol by lipoproteins required the interaction of apolipoprotein B or apolipoprotein E with specific receptors on normal lymphocytes. Apolipoprotein modification by acetylation or methylation, which markedly reduced the ability to regulate sterol biosynthesis, also diminished the capacity of lipoproteins to provide cholesterol. In addition, depletion of apolipoprotein B- and apolipoprotein E-containing particles from high density lipoprotein decreased its ability to suppress cholesterol synthesis and prevented it from providing cholesterol to proliferating lymphocytes. Monoclonal antibodies directed against the receptor-recognition sites on apolipoprotein B and apolipoprotein E were used to define the specific apolipoproteins required for the provision of cholesterol to lymphocytes by the various lipoprotein fractions. The antibody to apolipoprotein B inhibited cholesterol provision by both low density lipoprotein (LDL) and other lipoprotein fractions. The antibody to apolipoprotein E did not decrease provision of cholesterol by LDL but did inhibit the capacity of other fractions to provide cholesterol. In addition, a monoclonal antibody against the ligand binding site on the LDL receptor inhibited provision of cholesterol to normal lymphocytes by all lipoproteins. Finally, lymphocytes lacking LDL receptors were unable to obtain cholesterol from any lipoprotein fraction. These studies demonstrate that LDL receptor-mediated interaction with apolipoprotein B or apolipoprotein E is essential for the provision of cholesterol to normal human lymphocytes from all lipoprotein sources.     

Multiplicative background correction for spotted microarrays to improve reproducibility

We propose a simple approach, the multiplicative background correction, to solve a perplexing problem in spotted microarray data analysis: correcting the foreground intensities for the background noise, especially for spots with genes that are weakly expressed or not at all. The conventional approach, the additive background correction, directly subtracts the background intensities from foreground intensities. When the foreground intensities marginally dominate the background intensities, the additive background correction provides unreliable estimates of the differential gene expression levels and usually presents M-A plots with fishtails or fans. Unreliable additive background correction makes it preferable to ignore the background noise, which may increase the number of false positives. Based on the more realistic multiplicative assumption instead of the conventional additive assumption, we propose to logarithmically transform the intensity readings before the background correction, with the logarithmic transformation symmetrizing the skewed intensity readings. This approach not only precludes the fishtails and fans in the M-A plots, but provides highly reproducible background-corrected intensities for both strongly and weakly expressed genes. The superiority of the multiplicative background correction to the additive one as well as the no background correction is justified by publicly available self-hybridization datasets.