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Biomedical subjects

G M Saidel

Publications and source records attributed to G M Saidel.

At least 91 records · Page 5Linked to original sources

Human lung pressure-volume relationships: alveolar collapse and airway closure.

We investigated the effect of airway closure and alveolar collapse on the large-volume deflation and inflation transpulmonary pressure-volume (Ptp-V) curves of five postmortem excised human lungs. For stepwise static cycles, no inflection occurred on the deflation curve, while either one or two inflections occurred on the inflation curve. These relations were stimulated by a multicompartment model, which assumed a bimodal distribution of compartmental collapse-pressure differences. The simulations indicate that alveolar collapse can occur without causing an inflection on the deflation curve and that hysteresis in reopening of collapsed alveoli on inflation can account for a major portion of Ptp-V hysteresis. In contrast, for slow dynamic cycles, an inflection occurred on the experimental deflation Ptp-V curve, and when inflations were begun at sufficiently low volumes, volume did not change until a threshold pressure difference was reached about which PtP began to oscillate as lung volume increased. These differences in the stepwise static and dynamic Ptp-V curves can result from sustained airway closure on deflation and popping-opening on inflation.

Humans↗

Ventilation inhomogeneity using multibreath nitrogen washout: comparison of moment ratios and other indexes.

In this study we compared a variety of indexes of ventilation inhomogeneity based on multibreath nitrogen washout of the lungs. We studied 40 subjects in 5 clinical groups: 6 normal subjects, 5 "normal" smokers, 6 subjects with asthma, 13 with diffuse interstitial lung disease (DILD), and 10 with chronic obstructive pulmonary disease (COPD). We found that a moment ratio (micron 1/micron 0), which is a mean dilution number (or number of volume turnovers), is superior to other indexes studied with respect to minimal intrasubject variability and maximal diagnostic sensitivity. Even minimal ventilation inhomogeneity could be detected in "normal" smokers, as evidenced by the difference in micron 1/micron 0 values from those found in normal nonsmokers. As a group, asthmatics showed mild ventilation inhomogeneity, with greater variation depending on their functional status at the time of testing. Subjects with DILD tended to have moderate ventilation inhomogeneity, which appeared to increase with age. As expected, the greatest ventilation inhomogeneity occurred in COPD.

Adult↗

Real-time moment analysis of pulmonary nitrogen washout.

A real-time moment analysis was applied to multibreath nitrogen-washout dynamics of the lung. Because the analysis accounts for breathing pattern variations, subjects could perform the washout with spontaneous breathing. The real-time digital processing of the nitrogen and flow signals incorporates filtering, delay compensation, and corrections for the effects of gas composition and temperature changes. In our study, moment analysis of the multibreath washout was evaluated for 37 subjects: 6 normal nonsmokers, 4 "normal" smokers, 6 asthmatics, 12 with diffuse interstitial disease, and 9 with chronic obstructive pulmonary disease. Moments were computed from end-tidal and breath-averaged nitrogen fractions. The ratio of 1st-to-0th moments was found to yield distinctions among subjects with different degrees of ventilation inhomogeneity, even between normal nonsmokers and "normal" smokers. With minimal computational facilities, this moment analysis not only provides a sensitive index of ventilatory dysfunction, but also a cost-effective tool.

Adult↗

Quantitative analysis of renal medullary anatomy in rats and rabbits.

The mean renal tubular diameters, number of tubules per unit of cross-sectional area, and fraction of the total volume occupied by each medullary structure were determined at various levels of the renal medulla of the rat and rabbit. Statistical estimates of anatomic variables were made using spatial sampling techniques on histologic sections. Osmotic diuresis and renal venous occlusion were used to allow fixation of renal tubules and blood vessels in an open state. The distribution of volume fractions of medullary structures are similar in rats and rabbits. Diameters of outer medullary tubular segments and inner medullary thin limbs of Henle are also similar in rats and rabbits. Marked differences between rats and rabbits, however, are seen in the size and number of collecting ducts in the inner medulla. Rabbit inner medullary collecting ducts increase in diameter and decrease in number in the papillary direction relatively closer to the cortex than do those of the rat. Luminal diameters of papillary collecting ducts are more than twice as great in the rabbit as in the rat. An additional finding was that short loops of Henle in the rabbit have their bends relatively closer to the cortex than those of the rat. The quantitative anatomic data derived in this study, when combined through mathematical modeling with knowledge of transport properties of renal tubular membranes, should lead to a clearer understanding of renal function.

Animals↗

Comparison of measures of forced expiration.

Theoretical relationships among a number of parameters were derived for idealized timed vital capacity (TVC) and maximal expiratory flow-volume (MEFV) curves to determine a minimal set of independent parameters. Normal pediatric subjects and those with cystic fibrosis were studied to verify these relationships experimentally. The average flow over the middle half (FEF25-75%) of the forced vital capacity (FVC) and flows at various exhaled percentages of the FVC (FEF50%, FEF75%), as well as moments of the TVC and MEFV curves were computed. From the TVC moments, a mean transit time (MTT) and an index of dispersion (ID) were also calculated. The minimum information needed to detect pulmonary mechanical changes associated with obstructive lung disease requires at least two reproducible measures: one related to the mean slope (e.g., FEF25-75%/FVC or MTT) and the other to the shape (e.g;, ID) of the effort-independent portion of the MEFV curve.

Adolescent↗

Mechanism of Bacillus Calmette-Guérin-induced suppression of metastases in a poorly immunogenic fibrosarcoma.

Bacillus Calmette-Guérin (BCG) reduces the rate of spontaneous pulmonary metastases from a poorly immunogenic fibrosarcoma. To be effective, BCG (1 X 10(6) organisms) must be given in admixture with (1 X 10(6)) tumor cells at the time of transplantation. Reduction of metastasis at this dosage of BCG occurs without a change in the size of the primarytumor or the extent of necrosis within it. Tumors transplanted in admixture with spleen cells from BCG-exposed donors reduced the number of metastases, while spleen cells from normal or tumor-bearing donors had no effect on metastases. Fewer total tumor cells and clumps are collected from the venous effluent of tumors transplanted with BCG than from control tumors. The BCG-treated tumors have more host macrophages intimately associated with the effluent tumor cells then did controls. These data indicate that BCG can inhibit the metastatic potential of a weakly immunogenic fibrosarcoma. The mechanism of this effect appears to be a depression of entry or tumor cells into the tumor vascular channels which may be related to the interaction of tumor cells with BCG-stimulated macrophages.

Animals↗

Stochastic model of metastases formation.

A mathematical model is developed to describe the dynamics of the hematogenous metastatic process to the lung from a solid tumor growing in a peripheral body site. The accumulation of tumor cell clumps of various sizes in the pulmonary circulation and the formation of metastatic foci are described by a non-homogeneous, two-dimensional Markov process. An analytical solution is found for the special case of metastases produced by the intravenous injection of tumor cell clumps. The system is decoupled experimentally to determine the time-varying entrance rate of tumor cell clumps into the circulation from a growing fibrosarcoma and the number of metastatic foci produced by the intravenous injection of tumor clumps. Model validation is based on comparisons of model simulations with data for the development of metastatic foci and the probability of cure following tumor excision. The model is used to simulate hypothetical therapy to prevent tumor metastases.

Animals↗

Effects of dietary protein restriction and glucocorticoid administration on urea excretion in rats.

Rats were sampled for clearance studies under anesthesia after 0, 2, 4, 7 and 14 days of dietary protein restriction. Mean fractional urea excretion decreased between day 2 and day 7 of protein restriction after a two-day lag in response. Seven-day administration of dexamethasone in protein-restricted rats caused a significant increase in mean fractional urea excretion. Adrenalectomized rats fed a normal diet had fractional urea excretion values resembling those in protein-restricted rats. Chronic administration of dexamethasone in adrenalectomized rats caused a consistent increase in fractional urea excretion. Fractional urea excretion values were no lower in protein-restricted adrenalectomized rats fed a normal diet. The mean plasma corticosterone concentration (measured 6 to 8 PM) was decreased in rats fed a low protein diet relative to rats fed a high protein diet. The results suggest that glucocorticoids may play a role in the tubular regulation of urea excretion either by a direct effect on the renal tubule or through some intermediate factor. A mediating role of glomerular filtration rate in glucocorticoid-induced changes of fractional urea excretion could not be ruled out, however.

Adrenalectomy↗

Moment analysis of multibreath lung washout.

A moment analysis of multibreath nitrogen washout has been developed to provide a sensitive, quantitative measure that characterizes the inhomogeneity of pulmonary ventilation. To test the analysis scheme, we studied 5 normal subjects and 16 subjects with obstructive lung disease who performed each washout test at constant tidal volume and frequency. Subjects executed the wahout test 3-4 times at different tidal volumes (0.5-1.5 liters) and frequencies (10-30/min). Plotting washout data as dimensionless end-tidal nitrogen concentration versus the cumulative expired volume normalized by the functional residual capacity (CEV/FRC) renders the washout curves of each individual almost superposab le despite changes in breathing frequency and tidal volume from test to test. The dimensionless washout curve is treated as a distribution from which the normalized first (M1/Mo) and second (M2/Mo) moments are obtained. These parameters clearly display diagnostic clustering for various disease states. With respect to the normal subjects, the magnitude of M1/Mo was 26% greater for asthmatics, 38% greater for bronchitics, and 52% greater for emphysematics. This moment analysis provides an objective, quantitative assessment of the extent of ventilation inhomogeneities without specification of a lung model.

Airway Obstruction↗