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Biomedical subjects

I D Frantz

Publications and source records attributed to I D Frantz.

At least 19 recordsLinked to original sources

Measurement of low-density-lipoprotein cholesterol in serum: a status report.

Current recommendations of the Adult Treatment Panel and the Children and Adolescents Treatment Panel of the National Cholesterol Education Program make the concentration of low-density lipoproteins cholesterol (LDL-C) in serum the basis for the classification and treatment of hypercholesterolemia. Numerous methodologies for the determination of serum LDL-C concentrations, in research and clinical laboratories, have been described. Here, we review the principles, performance, and limitations of major current methodologies for determining LDL-C concentrations. These methods include sequential and density-gradient ultracentrifugation, chromatographic and electrophoretic techniques, and precipitation methods. In addition, the advantages and disadvantages of estimating LDL-C concentration by the Friedewald equation, the most commonly used approach in clinical laboratories, are addressed.

Chemical Precipitation

Effect of mean airway pressure on gas exchange during high-frequency oscillatory ventilation.

We studied the effect of mean airway pressure (Paw) on gas exchange during high-frequency oscillatory ventilation in 14 adult rabbits before and after pulmonary saline lavage. Sinusoidal volume changes were delivered through a tracheostomy at 16 Hz, a tidal volume of 1 or 2 ml/kg, and inspired O2 fraction of 0.5. Arterial PO2 and PCO2 (PaO2, PaCO2), lung volume change, and venous admixture were measured at Paw from 5 to 25 cmH2O after either deflation from total lung capacity or inflation from relaxation volume (Vr). The rabbits were lavaged with saline until PaO2 was less than 70 Torr, and all measurements were repeated. Lung volume change was measured in a pressure plethysmograph. Raising Paw from 5 to 25 cmH2O increased lung volume by 48-50 ml above Vr in both healthy and lavaged rabbits. Before lavage, PaO2 was relatively insensitive to changes in Paw, but after lavage PaO2 increased with Paw from 42.8 +/- 7.8 to 137.3 +/- 18.3 (SE) Torr (P less than 0.001). PaCO2 was insensitive to Paw change before and after lavage. At each Paw after lavage, lung volume was larger, venous admixture smaller, and PaO2 higher after deflation from total lung capacity than after inflation from Vr. This study shows that the effect of increased Paw on PaO2 is mediated through an increase in lung volume. In saline-lavaged lungs, equal distending pressures do not necessarily imply equal lung volumes and thus do not imply equal PaO2.

Animals

Determination of serum cholesterol by isotope dilution mass spectrometry with a benchtop capillary gas chromatograph/mass spectrometer: comparison with the National Reference System's Definitive and Reference Methods.

We developed an isotope dilution mass spectrometric cholesterol method with [25,26,27-13C]cholesterol as internal standard and a benchtop gas chromatograph/mass spectrometer (GC/MS) that is much easier and less time consuming than previously described Reference and Definitive Methods for cholesterol. The internal standard, cholesterol standards, and unknown specimen are delivered volumetrically with an automated dilutor and the saponifying reagent. After saponification, extraction, and derivatization, specimens are injected into a benchtop quadrupole MS with an autosampler. Unknown cholesterol concentrations are calculated automatically by comparing the peak area ratio of the m/z = 368, 371 ion pair with the ratios for the cholesterol standards (0 to 12.93 mmol/L). We found within-run and day-to-day (overall) imprecision of 0.44% and 0.95%, respectively, when specimens were assayed singly. In several lyophilized and frozen Standard Reference Material (SRM) pools, cholesterol results with our GC/MS method averaged 0.4% less than the National Institute for Standards and Technology definitive GC/MS result performed about three years earlier. Our GC/MS results averaged 1.3% and 2.0% less than results by the National Reference System (NRS) Abell-Levy-Brodie-Kendall (ALBK) results from clinical specimens and the SRM pools, respectively. These results are consistent with the previously reported bias between the NRS Reference and Definitive Methods and the 0.1% per year decrease in cholesterol concentrations in SRM pools as determined by GC/MS analysis. These results further emphasize the small but consistent bias between cholesterol results by isotope dilution mass spectrometry and the ALBK Reference Method, the latter being the basis for the National Cholesterol Education Program guidelines and population reference values.

Cholesterol

Improved neonatal survival following multiple doses of bovine surfactant in very premature neonates at risk for respiratory distress syndrome.

To determine whether multiple doses of bovine surfactant would improve neonatal mortality in very premature neonates, we conducted two multicenter controlled trials under identical protocols; the results were combined for analysis. Four hundred and thirty neonates born between 23 and 29 weeks gestation and weighing 600 to 1250 g at birth were assigned randomly at birth to receive either 100 mg of phospholipids/kg of Survanta, a modified bovine surfactant (n = 210), or a sham air placebo (n = 220) within 15 minutes of birth. Neonates who developed respiratory distress syndrome and required mechanical ventilation with at least 30% oxygen could be given up to three more doses in the first 48 hours after birth. Dosing was performed by investigators not involved in the clinical care of the neonates; nursery staff were kept blinded as to the treatment assignment. Cause of death was determined by a panel of three independent, board-certified neonatologists after blindly reviewing case report forms and autopsy reports. Fewer Survanta-treated neonates died of any cause (11.4% vs 18.8%, P = .031), died of respiratory distress syndrome (1.9% vs 15.6%, P less than .001), and either died or developed bronchopulmonary dysplasia due to respiratory distress syndrome (39.5% vs 49.1%, P = .044). The incidence of respiratory distress syndrome was also lower in Survanta-treated neonates (28.0% vs 56.9%, P less than .001), and the Survanta-treated neonates' oxygenation and ventilatory status were improved significantly at 72 hours. Survanta-treated neonates were also at lowered risk of developing pulmonary interstitial emphysema (23.3% vs 36.9%, P = .002) and other forms of pulmonary air leaks (9.6% vs 20.8%, P .002).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation

Frequency, tidal volume, and mean airway pressure combinations that provide adequate gas exchange and low alveolar pressure during high frequency oscillatory ventilation in rabbits.

We studied healthy and saline lavaged rabbits during high frequency oscillatory ventilation to determine what combination of frequency (f), tidal volume (Vt), and mean airway pressure (Paw) produced the lowest peak-to-peak alveolar pressure amplitude (Palv) and physiologic blood gas tensions. Sinusoidal volume changes were delivered through a tracheostomy by a piston pump driven by a linear motor. Tracheal pressure amplitude (Ptr) was measured through a tracheal catheter and alveolar pressure amplitude was measured in a capsule glued to the right lower lobe. PaO2, PaCO2, Ptr, and Palv were measured at the following settings: FiO2 = 0.5, frequency 2-28 Hz, Vt 1-3 mL/kg (50 150% dead space) and Paw 5-15 cm H2O. Many combinations of frequency and Vt resulted in the same PaO2 and PaCO2. Paw had a large effect on Palv and minimal effect on blood gas tensions. In lavaged rabbits, the composite variable f x Vt2 described the trends in Palv and blood gas tensions. As the product of f x Vt2 increased, PaO2 initially increased and then decreased, whereas PaCO2 decreased and Palv increased. No single combination of frequency, Vt and Paw simultaneously provided the lowest Palv and physiologic blood gas tensions. Adequate blood gas tensions and low Palv were obtained at frequencies less than 12 Hz, a Vt of 2 mL/kg and a Paw of 10 cm H2O. In healthy and lavaged rabbits PaO2 increased and PaCO2 decreased as frequency increased at lower Vt.PaO2 decreased as frequency increased at higher Vt in lavaged rabbits only. Palv tended to be greater in lavaged rabbits.

Airway Resistance

Mechanics of the respiratory system during high frequency ventilation.

No rational approach has evolved for selecting operating conditions for clinical application of high-frequency ventilation (HFV). To this end, we divide our discussion of HFV into considerations of mechanics versus transport, and treat the latter as a constraint. After describing some of the phenomena that influence distending pressure (and its distribution) expressed across pulmonary tissues, we address the pressure costs per unit ventilation and the factors that influence them. This narrowly defined approach leads to some fundamental strategies, compromises, and dilemmas. In particular, consideration of the mechanical interaction of the lung and chest wall leads to a paradox, and points out that the influence of the chest wall upon phasic regional lung distension is not well understood.

Animals

Preferential axial flow during high-frequency oscillations: effects of gas density.

Allen et al. (J. Clin. Invest. 76: 620-629, 1985) reported that regional phasic lung distension during high-frequency oscillations (HFO) is substantially and systemically heterogeneous when both frequency (f) and tidal volume (VT) are large. They hypothesized that this phenomenon was attributable to central airway geometry and preferential axial flow induced therein by the momentum flux of the inspiratory gas stream. According to that hypothesis, the observed distribution of phasic lung distension would depend on the ratio VT/VD* (where VD* is an index of anatomic dead space), independent of gas density (rho), when f is scaled in proportion to lung resonant frequency, fo. To test this hypothesis, we used the methods of Allen et al. (ibid.) to study six excised dog lungs during HFO (f = 2-32 Hz; VT = 5-80 ml) using gases of different densities. Alveolar pressure excursions (PA) were measured as rho spanned a 12-fold range using He, air, and SF6. The apex-to-base and right-to-left ratios of PA were used as indexes of regional heterogeneity of phasic lung distension. For each gas at low f, distension of the lung base was favored slightly independent of VT, but at higher f distension of the lung apex was favored when VT was small, whereas distension of the lung base was favored when VT was large. In addition, we observed substantial right-to-left differences in apical lobes during oscillation at high f not seen before.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Gas exchange in healthy rabbits during high-frequency oscillatory ventilation.

We examined the effects of oscillatory frequency (f), tidal volume (VT), and mean airway pressure (Paw) on respiratory gas exchange during high-frequency oscillatory ventilation of healthy anesthetized rabbits. Frequencies from 3 to 30 Hz, VT from 0.4 to 2.0 ml/kg body wt (approximately 20-100% of dead space volume), and Paw from 5 to 20 cmH2O were studied. As expected, both arterial partial pressure of O2 and CO2 (PaO2 and PaCO2, respectively) were found to be related to f and VT. Changing Paw had little effect on blood gas tensions. Similar values of PaO2 and PaCO2 were obtained at many different combinations of f and VT. These relationships collapsed onto a single curve when blood gas tensions were plotted as functions of f multiplied by the square of VT (f. VT2). Simultaneous tracheal and alveolar gas samples showed that the gradient for PO2 and PCO2 increased as f. VT2 decreased, indicating alveolar hypoventilation. However, venous admixture also increased as f. VT2 decreased, suggesting that ventilation-perfusion inequality must also have increased.

Animals

Mixed and obstructive apneas are related to ventilatory oscillations in premature infants.

In our previous study of 14 premature infants, apnea occurred at the minimum phase of ventilatory oscillations. The apneas corresponded to cessation of airflow at the nose and mouth and were not distinguished as central, mixed, or obstructive. Changes in heart rate associated with the apneas were not identified. To determine whether ventilatory pattern characteristics might predict either the type of apnea or heart rate changes during the apnea, we analyzed measurements of chest wall movement and heart rate that were made during the earlier studies. Chest wall movement measured by magnetometers was compared with airflow measured with a face mask and pneumotachograph. Tidal volume, breath duration, and ventilation were calculated on a breath-by-breath basis, converted to time-axis data strings, and filtered with a comb of zero phase shift digital band-pass filters to detect breathing patterns. Of 182 apneas greater than or equal to 3 s duration, 55% were central, 31% were mixed, and 14% were obstructive. All three types of apnea were related to ventilatory oscillations. Multiple linear and logistic regressions showed that an apnea was more likely to be obstructive when it was long and when the underlying ventilatory oscillation was due primarily to an oscillation in breath duration. Multiple linear and logistic regressions showed that decreases in heart rate were related primarily to the duration of apnea and secondarily to the characteristics of the underlying breathing patterns.

Airway Obstruction

Rib cage vs. abdominal displacement in dogs during forced oscillation to 32 Hz.

Allen et al. (J. Clin. Invest. 76: 620-629, 1985) reported that during oscillatory forcing the base of isolated canine lungs distends preferentially relative to the apex as frequency and tidal volume increase. The tendency toward such nonuniform phasic lung distension might influence phasic displacement of the rib cage (RC) relative to the abdomen (ABD). To test this hypothesis we measured RC and ABD displacement in four anesthetized dogs during forced oscillation. Sinusoidal volume changes were delivered through a tracheostomy at 1-32 Hz and measured by body plethysmography. RC and ABD displacements were measured by inductive plethysmography. During oscillation with air at fixed tidal volumes (10-80 ml) RC, normalized to unity at 1 Hz, increased to 2.06-2.22 at 8 Hz (P less than 0.001) and then decreased to 1.06-1.35 (P less than 0.0025) at 32 Hz. ABD, normalized to unity at 1 Hz, was 1.12-1.16 at 4 Hz (P less than 0.001) and decreased to 0.12-0.14 at 32 Hz (P less than 0.001). Displacement of ABD relative to RC did not increase systematically with increasing tidal volume during sinusoidal forcing at any frequency. Thus we found no discernible influence of nonuniform phasic lung distension on chest wall behavior. We infer that in the dog the nonuniform mechanical behavior of the chest wall dominates the nonuniform (but opposing) mechanical tendency of the lung.

Abdomen

Cardiovascular risk factor change--1973-74 to 1980-82: the Minnesota Heart Survey.

Reductions in population risk factor levels, including blood pressure, blood cholesterol, and cigarette smoking may be associated with the observed decline in cardiovascular disease (CVD) mortality rates. However, few recent population-based comparisons of risk trends are available. To evaluate changes in these risk characteristics in the recent period, data were compared from two surveys performed in the same metropolitan area using similar methods. The Lipid Research Clinic (LRC) Prevalence Study surveyed a population sample of 4185 adults aged 25-59 in 1973-74. The Minnesota Heart Survey (MHS) surveyed a population sample of 2914 adults of the same age in the same metropolitan area in 1980-82. The average systolic and diastolic blood pressures were significantly lower in the 1980-82 survey averaging 1.5/3.8 mmHg for men and 1.6/2.8 mmHg for women. The use of anti-hypertensive medications increased significantly over the period while the prevalence of hypertension was similar. Significant declines in mean serum cholesterol were also observed in 1980-82, averaging 3.3 mg/dl for men and 5.5 mg/dl women. The prevalence of regular cigarette smoking in men was also lower in 1980-82, 36.3 vs 42.1% in 1973-74. Women had a lower prevalence of smoking (38.8-35.6%) but the average woman smoker increased consumption of cigarettes while the average man did not. These observations suggest that population risk defined by these characteristics is declining which may explain part of recent Minnesota trends in CVD mortality and could have a favorable effect on future disease patterns.

Adult

Heterogeneity of mean alveolar pressure during high-frequency oscillations.

Mean alveolar pressure may exceed mean airway pressure during high-frequency oscillations (HFO). To assess the magnitude of this effect and its regional heterogeneity, we studied six excised dog lungs during HFO [frequency (f) 2-32 Hz; tidal volume (VT) 5-80 ml] at transpulmonary pressures (PL) of 6, 10, and 25 cmH2O. We measured mean pressure at the airway opening (Pao), trachea (Ptr), and four alveolar locations (PA) using alveolar capsules. Pao was measured at the oscillator pump, wherein the peak dynamic head was less than 0.2 cmH2O. Since the dynamic head was negligible here, and since these were excised lungs, Pao thus represented true applied transpulmonary pressure. Ptr increasingly underestimated Pao as f and VT increased, with Pao - Ptr approaching 8 cmH2O. PA (averaged over all locations) and Pao were nearly equal at all PL's, f's, and VT's, except at PL of 6, f 32 Hz, and VT 80 ml, where (PA - Pao) was 3 cmH2O. Remarkably, mean pressure in the base exceeded that in the apex increasingly as f and VT increased, the difference approaching 3 cmH2O at high f and VT. We conclude that, although global alveolar overdistension assessed by PA - Pao is small during HFO under these conditions, larger regional heterogeneity in PA's exists that may be a consequence of airway branching angle asymmetry and/or regional flow distribution.

Animals

Regulation of end-expiratory lung volume during sleep in premature infants.

To investigate the regulation of end-expiratory lung volume (EEV) in premature infants, we recorded airflow, tidal volume, diaphragm electromyogram (EMG), and chest wall displacement during sleep. In quiet sleep, EEV during breathing was 10.8 +/- 3.6 (SD) ml greater than the minimum volume reached during unobstructed apneas. In active sleep, no decrease in EEV was observed during 28 of 35 unobstructed apneas. Breaths during quiet sleep had a variable extent of expiratory airflow retardation (braking), and inspiratory interruption occurred at substantial expiratory flow rates. During active sleep, the expiratory flow-volume curve was nearly linear, proceeding nearly to the volume axis at zero flow, and diaphragm EMG activity terminated near the peak of mechanical inspiration. Expiratory duration (TE) and inspiratory duration (TI) were significantly shortened in quiet sleep vs. active sleep although tidal volume was not significantly different. In quiet sleep, diaphragmatic braking activity and shortened TE combined to maintain EEV during breathing substantially above relaxation volume. In active sleep, reduced expiratory braking and prolongation of TE resulted in an EEV that was close to relaxation volume. We conclude that breathing strategy to regulate EEV in premature infants appears to be strongly influenced by sleep state.

Diaphragm

Factors influencing mechanical performance of neonatal high-frequency ventilators.

Factors influencing the mechanical performance of neonatal high-frequency ventilators of diverse design were assessed under controlled conditions. Each of eight ventilators was coupled to in vitro models of the neonatal respiratory system simulating disease of varying severity. The principal performance characteristics examined were frequency dependence and load dependence of tidal volume delivered, peak inspiratory flow rate, and waveforms of pressure at either end of the endotracheal tube. Despite wide diversity of ventilator designs, including jets, flow interrupters, and oscillators, common features emerged. In almost all devices tidal volume increased with endotracheal tube size, was invariant with respiratory system compliance, and decreased with frequency of oscillation. Peak inspiratory flow rates for a given tidal volume and frequency were smallest in the group of oscillators compared with jets and flow interrupters. Proximal pressure was a poor indicator of distal pressure. These findings suggest that delivered tidal volume may be sensitive to endotracheal tube size and airway patency but relatively insensitive to changes in lung tissue or chest wall mechanical properties. In these regards high-frequency ventilation differs from pressure-limited conventional mechanical ventilation. Comparison of data obtained at different clinical centers using high-frequency ventilators of varying design may be possible by taking these factors into account.

Humans

Rib cage versus abdominal displacement in rabbits during forced oscillations to 30 Hz.

We measured relative displacement of the rib cage (RC) and abdomen (ABD) in 12 anesthetized rabbits during forced oscillations. Sinusoidal volume changes were delivered through a tracheostomy at frequencies from 0.5 to 30 Hz and measured by body plethysmography. Displacements of the RC and ABD were measured by inductive plethysmography. During oscillation at fixed tidal volume (VT = 1.3 ml/kg) the ratio ABD/RC, normalized to unity at 0.5 Hz, was 0.88 +/- 0.06 at 2 Hz and increased to 1.28 +/- 0.13 at 6 Hz (P less than 0.01). As frequency increased further ABD/RC fell sharply but between 20 and 30 Hz reached a plateau of 0.17 +/- 0.02 (P less than 0.001). Displacements of RC and ABD were nearly synchronous from 0.5 to 2 Hz, but as frequency increased ABD lagged RC progressively, reaching a phase difference of 90 degrees between 6 and 8 Hz and 180 degrees between 16 and 20 Hz. In six additional rabbits we measured chest wall displacements while varying VT from 0.5 to 3.7 ml/kg. ABD/RC was independent of VT at low frequencies (less than or equal to 6 Hz) but fell sharply with increasing VT at the higher frequencies. We interpreted these findings using a chest wall model having an RC compartment whose displacements are governed primarily by a nonlinear compliance, in parallel with an ABD compartment whose displacements are governed by a series resistance, inertance, and in addition a nonlinear compliance. The experimental findings are in large measure accounted for by such a model if the degree of nonlinearity of ABD and RC compliances are comparable.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen

Respiratory distress syndrome.

Increasing knowledge of the pathophysiology of respiratory distress syndrome has led to improvements in clinical management. Future advances in prevention and therapy, including administration of agents to prevent prematurity or to accelerate lung maturation, provision of surfactant replacement, and new techniques of mechanical ventilation, will further decrease mortality and morbidity.

Animals