Biomedical subjects

H A Feldman

Publications and source records attributed to H A Feldman.

At least 91 records · Page 5Linked to original sources

PubMed1989

Effect of cystic fibrosis on inhaled aerosol boluses.

An aerosol bolus undergoes changes in shape between its inspiration and expiration. In comparison with the inhaled bolus, the exhaled bolus is more spread because of convective mixing, may have a shift in the location of the mode caused by asymmetries of filling and emptying of lung units, and contains fewer particles because of particle deposition. We hypothesized that the extent of these changes is related to lung health. To examine this, 11 patients with cystic fibrosis (CF) and 11 healthy subjects inhaled 70 cm3 boluses containing 1 micron monodisperse particles that were inspired to volumetric penetrations (Vp) of 100 to 700 cm3. As each bolus was expired, we measured spreading (volumetric width at one-half aerosol concentration peak height), modal shift, and particle deposition. Patients with CF exhaled boluses that were broader than those exhaled by normal subjects at all penetrations examined. At a Vp of 600 cm3, patients had a mean bolus half-width that was 68% greater than that of healthy subjects (p less than 0.0001), and they exhaled the bolus mode 20% earlier (p less than 0.0002). Particle deposition was increased compared with that in normal subjects at all Vp. For example, mean deposition at a Vp of 600 cm3 was 46.2 +/- 2.6% (SE) for the patients versus 25.8 +/- 1.6% for the normal subjects (p less than 0.0001). Among the patients with CF, pulmonary function parameters indicating obstruction were significantly correlated with bolus spreading and aerosol deposition: the percent predicted FEV1/FVC was inversely correlated with spreading (r = -0.88, p less than 0.0004) and deposition (r = -0.84, p less than 0.0008).(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗

PubMed1988

Beryllium exposure and pulmonary function: a cross sectional study of beryllium workers.

A cross sectional study of 297 white male workers employed in a large beryllium plant was conducted to test the hypothesis that long term exposure to beryllium is associated with decrements in pulmonary function. Spirometric measurement of pulmonary function, chest radiographs, and arterial blood gas measurements were collected. After controlling for age, height, and smoking in multivariate regression models, decrements in FVC and FEV1 were found to be associated with cumulative exposure to beryllium in the period up until 20 years before the health survey. These decrements were observed in workers who had no radiographic abnormalities. The alveolar-arterial oxygen difference was associated with cumulative exposure in the 10 years immediately before survey, after controlling for age and smoking. These findings suggest that beryllium may have both short and long term pulmonary effects that are distinct from the classic forms of acute and chronic beryllium disease.

Adult↗

PubMed1988

Convective mixing in human respiratory tract: estimates with aerosol boli.

Convective gas mixing in the respiratory tract of 17 healthy male subjects was studied by an aerosol bolus technique. The monodisperse 1 micron di(2-ethylhexyl)sebacate droplets we used behaved as a nondiffusing gas. As the bolus was inspired to different depths and then expired, we measured the extent to which the bolus spread. We found that the deeper the bolus penetrated into the lungs, the more it became dispersed. The half-width of the expired bolus was a linear function of the volume to which the bolus penetrated at volumetric penetrations of 100-800 cm3. This suggests that convective mixing is not confined to central airways but can also occur in the lung periphery.

Adult↗

PubMed1988

Families of lines: random effects in linear regression analysis.

Laboratory experiments often involve two groups of subjects, with a linear phenomenon observed in each subject. Simple linear regression as propounded in standard textbooks is inadequate to treat this experimental design, particularly when it comes to dealing with random variation of slopes and intercepts among subjects. The author describes several techniques that can be used to compare two independent families of lines and illustrates their use with laboratory data. The methods are described tutorially, compared, and discussed in the context of more sophisticated and more naive approaches to this common data-analytic problem. Technical details are supplied in APPENDIX A.

Adolescent↗

PubMed1988

Control of inspiratory duration in premature infants.

We used single-breath mechanical loads and airway occlusions in premature infants to determine whether maturation influences the reflex control of inspiratory duration. We measured flow, volume, airway pressure, and surface diaphragmatic electromyogram (EMG) in 10 healthy preterm infants [33 +/- 1 (SD) wk gestation], 2-7 days of age. Three resistive and two elastic loads and occlusions were applied to the inspiratory outlet of a two-way respiratory valve. Application of all loads resulted in inspired volumes significantly decreased from control (P less than 0.001), and these decreases were progressive with increasing loads. Inspiratory duration (TI) was prolonged from control by all loads and occlusions when measured from the diaphragmatic EMG (neural TI) and by all but the smaller elastic load when measured from the flow tracing (mechanical TI). Similar decreases in inspired volume at the end of neural TI produced by application of both elastic and resistive loads resulted in comparable prolongation of neural TI. In contrast, for comparable volume decrements, resistive loading prolonged mechanical TI more than elastic loading (P less than 0.001). Mechanical and neural TI values of the breath after the loaded breath were unchanged from control values. Comparison of the neural volume-timing relationship in premature infants with our data in full-term infants suggests that the strength of the timing response to similar relative decrements in inspired volume is comparable. We conclude that reflex control of neural TI in premature infants depends on the magnitude of inspired volume and is independent of the volume trajectory.(ABSTRACT TRUNCATED AT 250 WORDS)

Diaphragm↗

PubMed1988

Relationship between maximal expiratory flows and lung volumes in growing humans.

We examined airway vs. lung parenchymal growth, as inferred from maximal expiratory flows (MEF) and lung volumes (V), respectively, to determine whether the interindividual variability of airway size (inferred from MEF) changes during lung growth and whether a young child with large (or small) airways for his parenchymal size (inferred from V) maintains relatively large (or small) airways for his lung size as he grows to adulthood. Serial measurements of MEF and V were obtained from a cohort of healthy 6- to 27-yr-old males (n = 26) and females (n = 21) over a period of 18 yr. Data were analyzed using logarithmic transformation of the power law equation, MEF = aVb, to fit a regression line to each subject's data points. These growth trajectories were satisfactorily modeled as parallel lines with 20-30% variability of their y-intercepts, indicating that substantial intersubject variability of MEF relative to V is present in early childhood and remains constant during growth. The results further indicate that MEF does track V during lung growth. We conclude that dysanapsis originates in early childhood.

Adolescent↗

PubMed1987

The pulmonary toxicity of talc and granite dust as estimated from an in vivo hamster bioassay.

A short-term animal bioassay was used to assess the toxicity of occupational dusts. We quantified pulmonary responses in hamsters exposed to granite (12% quartz) and talc (quartz and asbestos-free) dust collected from worksites. Personal samples collected on workers showed similar quartz content and particle-size distributions to the high-volume samples collected for bioassays, thus demonstrating that the particulates were representative of worker exposure. We measured biochemical and cellular indicators of injury in bronchoalveolar lavage fluid (BAL) of animals exposed to dust suspensions by intra-tracheal instillation. The assays measured release of cytoplasmic and lysosomal enzymes into the cell-free supernatant of BAL; levels of albumin and red blood cells; changes in macrophage and polymorphonuclear neutrophil cell numbers; and in situ macrophage phagocytosis. Dose-response (0.15, 0.75, and 3.75 mg/100 g body wt) and time-course (1-14 days postexposure) studies were performed. One day after exposure, both talc and granite dust resulted in elevated enzyme levels, pulmonary edema, and increased cell numbers in BAL. Macrophage phagocytosis was also inhibited. Based on earlier studies, response levels were either intermediate between nontoxic iron oxide and toxic alpha-quartz or comparable with alpha-quartz. The response to granite dust diminished fairly rapidly over time. By contrast, after talc exposure, there was a more persistent elevation in enzyme levels, and macrophage phagocytosis remained depressed. These results indicate that, when a similar mass was deposited in the lungs, talc caused more lung injury than did granite. Better estimates of exposure-dose relationships in talc and granite workers as well as longer-term animal studies are required to evaluate the harmfulness of these work environments at present-day exposure levels.

Animals↗

PubMed1987

Magnetic particle motions within living cells. Measurement of cytoplasmic viscosity and motile activity.

Submicrometer magnetic particles, ingested by cells and monitored via the magnetic fields they generate, provide an alternative to optical microscopy for probing movement and viscosity of living cytoplasm, and can be used for cells both in vitro and in vivo. We present methods for preparing lung macrophages tagged with magnetic particles for magnetometric study. Interpretation of the data involves fitting experimental remanent-field decay curves to nonlinear mechanistic models of intracellular particle motion. The model parameters are sensitive to mobility and apparent cytoplasmic viscosity experienced by particle-containing organelles. We present results of parameter estimation for intracellular particle behavior both within control cells and after (a) variable magnetization duration, (b) incubation with cytochalasin D, and (c) particle twisting by external fields. Magnetometric analysis showed cytoplasmic elasticity, dose-dependent motion inhibition by cytochalasin D, and a shear-thinning apparent viscosity.

Animals↗

PubMed1987

Adjusting for confounded variables: pulmonary function and smoking in a special population.

Confounded variables present an obstacle to valid inference in many environmental and occupational studies. We describe a series of procedures that we used to address this problem in a study of pulmonary function and smoking. Subjects were drawn from the Multiple Risk Factor Intervention Trial (MRFIT), a prospective study of coronary heart disease. Confounding of smoking, hypertension, and hyperlipidemia was designed into the trial and was beyond the control of our ancillary study. We used statistical techniques to detect and characterize the pattern of confounding, identify important variables affecting pulmonary function, and perform appropriate adjustments for extraneous influences (i.e., other than smoking). Among the techniques we used were factor analysis, stepwise multiple regression, and bootstrap replication. Analysis of the adjusted pulmonary function measurements showed that they were satisfactorily standardized and free of artifact. Moreover, use of the adjusted values sharpened our statistical results concerning smoking, the ultimate object of the study. We contrast the use of external and internal standards and discuss methods for detecting, ruling out, or counteracting confounding.

Adult↗

PubMed1987

Dimensional analysis does not determine a mass exponent for metabolic scaling.

In several recent article, Heusner used dimensional reasoning to derive important biological conclusions regarding the scaling of metabolism with body mass [Respir. Physiol. 48: 13-25, 1982; J. Appl. Physiol. 54: 867-873, 1983; Am. J. Physiol. 246 (Regulatory Integrative Comp. Physiol. 15): R839-R845, 1984]. We demonstrate errors in the derivation and show that dimensional analysis, correctly applied, not only fails to determine the mass scaling exponent but also fails to constrain the relationship to a power law at all.

Body Constitution↗

PubMed1987

Fiber types and fiber diameters in canine respiratory muscles.

In the present study, we measured fiber types and fiber diameters in canine respiratory muscles and examined regional variation within the diaphragm. Samples of eight diaphragm regions, internal intercostals, external intercostals, transversus abdominis, and triceps brachii were removed from eight adult mongrel dogs, frozen, and histochemically processed for standard fiber type and fiber diameter determinations. The respiratory muscles were composed of types I and IIa fibers; no IIb fibers were identified. Fiber composition differed between muscles (P less than 0.0001). Normal type I percent (+/- SE) were: diaphragm 46 +/- 2, external intercostal 85 +/- 6, internal intercostals 48 +/- 3, transversus abdominis 53 +/- 1, and triceps 33 +/- 7. The diaphragm also contained a type I subtype [6 +/- 1% (SE)] previously thought only to occur in developing muscle. Fiber composition varied between diaphragm regions (P less than 0.01). Most notably, left medial crus contained 64% type I fibers. Fiber size also varied systematically among muscles (P less than 0.025) and diaphragm regions (P less than 0.0005). External intercostal fiber diameter was largest (47-50 microns) and diaphragm was smallest (34 microns). Within diaphragm, crural fibers were larger than costal (P less than 0.05). We conclude that there are systematic differences in fiber composition and fiber diameter of the canine respiratory muscles.

Analysis of Variance↗

PubMed1987

Isometric contractile properties of diaphragm strips from alcoholic rats.

Chronic ethanol consumption alters the structure and function of human respiratory muscle. We have examined its effect on the active and passive mechanical properties of rat diaphragm strips in vitro. We conditioned eight rats using a liquid diet containing ethanol as 36% of calories. Eight control rats were pair-fed an isocaloric, ethanol-free liquid diet. Rats were killed after 23 wk. Two strips from the left hemidiaphragm were suspended in Krebs-Ringers solution at 25 degrees C, equilibrated with 5% CO2-95% O2. Isometric stresses were calculated from force transducer measurements. Strips were stimulated directly at supramaximal voltage. Twitch stress (Pt), measured at optimal length (Lo), was greater in ethanol-conditioned strips: 5.1 vs. 3.8 N/cm2. Times to peak Pt and twitch half-relaxation times were equal. Tetanic stress at Lo (Po) was also greater after ethanol conditioning: 17.2 vs. 12.8 N/cm2. Pt/Po ratios were equal. Expressed as %Po, tetanic stress-stimulation frequency curves and tetanic stress-length curves were identical. Ethanol-conditioned strips were marginally less compliant when passively stretched to lengths between Lo and 130% Lo. We postulate that ethanol may have increased active stress development by reducing intracellular free water.

Alcoholism↗

PubMed1987

Sulfur-dioxide-induced bronchitis in dogs. Effects on airway responsiveness to inhaled and intravenously administered methacholine.

Chronic bronchitis was induced in 7 dogs of mixed breed by chronic exposure to SO2 gas. Within the first 2 to 4 wk of exposure, the dogs developed cough and mucous hypersecretion, chronic airway obstruction (increased pulmonary resistance), and persistent lung inflammation as demonstrated by an increase in the number of neutrophils recovered in the bronchoalveolar lavage (BAL) fluid. Airway responsiveness to methacholine aerosol decreased 2- to 3-fold within 8 wk of SO2 exposure. In contrast, airway responsiveness to intravenous administration of methacholine did not change. The data suggest that the decreased airway responsiveness observed during persistent pulmonary inflammation in SO2-exposed dogs is not due to an altered state of airway contractile elements but likely reflects expression of an inhibitory influence of the mucoepithelial barrier.

Airway Resistance↗

PubMed1987

Randomized controlled trial of exogenous surfactant for the treatment of hyaline membrane disease.

We conducted a prospective, randomized, unblinded, controlled trial of exogenous bovine surfactant (surfactant TA) in premature infants requiring ventilator support for the treatment of severe hyaline membrane disease. Forty-one low birth weight infants with severe hyaline membrane disease were randomly assigned to saline or surfactant therapy and treated within eight hours of birth. Significant improvements in oxygenation (increased arterial/alveolar PO2) and respiratory support (decreased mean airway pressure) were seen in the group receiving surfactant within four hours after treatment. These improvements were maintained in the surfactant-treated infants, who also had fewer pneumothoraces and fewer number of days in environments of fractional inspiratory oxygen greater than 0.4 mm Hg. No problems were associated with administration of surfactant, and no acute side effects were detected. We conclude that exogenous surfactant, administered early in the course of severe hyaline membrane disease, is an effective therapy that can diminish the amount of respiratory support required during the first 48 hours of life.

Animals↗

PubMed1985

Estimation of PaCO2 by two noninvasive methods in the critically ill newborn infant.

Simultaneous measurements of arterial, transcutaneous, and peak expired carbon dioxide were obtained in 24 newborn infants receiving mechanical ventilation during the first week after birth. Two calibration algorithms designed to estimate PaCO2 from the noninvasive measurements were then examined. Both approaches entailed finding a statistical relationship by which future noninvasive measurement could be used to estimate the arterial value rather then measuring it directly. The first utilized the difference between the initial paired measurements (an in vivo calibration); the second used the mean difference between all measurements in the population. Adjusted tcPCO2 measurements by either the in vivo calibration or by the population-based factor led to estimates of PaCO2 with 95% confidence limits of +/- 6 to +/- 8 torr. In contrast, this degree of precision for the peak expired CO2 measurement was only possible using the in vivo calibration method. The use of an airway adaptor for PCO2 measurement led to CO2 retention in more than half of the infants. Transcutaneous monitoring had no significant effects on the infants, but was hampered by excessive drift and erratic sensitivity of the electrodes.

Blood Gas Analysis↗

PubMed1985

Reflex compensation of spontaneous breathing when immersion changes diaphragm length.

We measured tidal volume (VT), chest wall dimensions, end-tidal PCO2, and respiratory muscle electromyograms as seated subjects were immersed in water. We studied nine spontaneously breathing subjects; five were uninformed. Raising the water to xiphoid level pushed the abdomen in and expanded the rib cage at end expiration. This increased the diaphragm's operating length, giving it a contractile advantage, and shortened the inspiratory intercostals, giving them a contractile disadvantage. Peak inspiratory activities of both muscle groups decreased; inspiratory time (TI), respiratory frequency (f), and VT were unchanged. The experiments thus demonstrated operational length compensation during immersion and further showed that inspiratory muscle activation is not adjusted locally, according to changes in each muscle's length, but rather that the response is global. Xiphoid-to-shoulder immersion was less easily interpreted, since both rib cage and abdomen were compressed, lengthening both inspiratory muscles. Our subjects continued to maintain VT, f, and TI. Peak inspiratory activities of both muscles were further reduced. We do not attribute the change in inspiratory muscle activation to altered chemical drive or to voluntary response. Rather, the response appears to be a mechanoreceptive reflex that employs afferent information from the lungs or diaphragm to adjust all inspiratory muscle activities.

Diaphragm↗

PubMed1984

Naloxone does not affect ventilatory responses to hypoxia and hypercapnia in rats.

Ventilatory responses (tidal volume, respiratory frequency, and minute ventilation) to steady-state hypoxia and steady-state hypercapnia were measured plethysmographically in awake unrestrained adult rats, before and after subcutaneous injection of placebo (saline) naloxone in doses up to 5.0 mg/kg. Naloxone did not alter the ventilatory responses to hypoxia or hypercapnia.

Animals↗

PubMed1984

Insulin inhibition of tyrosine aminotransferase induction by dexamethasone is species-related.

Dexamethasone induces TAT in the embryonic chick liver, but this effect is not blocked by prior administration of insulin at a dose sufficient to increase the hepatic protein/DNA ratio. Similarly, insulin does not block dexamethasone induction of TAT in chick embryo hepatocytes in vitro. In contrast, insulin reduces TAT induction by dexamethasone in fetal rat hepatocytes by 35-40%. No significant differences in insulin binding were noted between chick and rat hepatocytes.

Animals↗