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Biomedical subjects

M Lippmann

Publications and source records attributed to M Lippmann.

At least 91 records · Page 5Linked to original sources
PubMed1986

Airborne particles, their use in the respiratory system to measure air flow, function, and clearance.

Nonhygroscopic monodisperse particles can be used to estimate airway dimensions within chosen regions of the respiratory tract. These dimensions correspond well with those measured in inflation-fixed lungs. The dispersion of a bolus of airborne particles on inhalation and exhalation is very sensitive to the dimensions of the airways through which the bolus passes, yielding indices of dispersion that provide sensitive indicators of changes in airway dimensions, eg, with smoking. The rates of clearance of particles from the lungs are determined using gamma-labelled particles whose lung retention is determined by external measurements. There are major differences between the deep lung and the ciliated airways. Changes in clearance rates are caused by disease or inhaled intoxicants such as cigarette smoke. At lower levels of irritant exposure, an acceleration of clearance rate is observed, while higher doses and longer periods of exposure produce decreased rates. It is suggested that aerosol techniques may have useful clinical applications; approaches are suggested for such applications.

Adult↗
PubMed1985

Effects of submicrometer sulfuric acid aerosols on mucociliary transport and respiratory mechanics in asymptomatic asthmatics.

The effects of a 1-hr inhalation of submicrometer sulfuric acid (H2SO4) aerosols via nasal mask on tracheobronchial mucociliary particle clearance and respiratory mechanics were studied in ten subjects with asthmatic histories. A brief inhalation of monodisperse 3.9-micron 99mTc-tagged Fe2O3 aerosol preceded the 1-hr H2SO4 (at 100, 300, and 1000 micrograms/m3) or a sham exposure. Thoracic retention of the gamma-tagged Fe2O3 was measured using external radiation detectors. Respiratory function was measured before, and 15 min and 3 hr after the H2SO4 or sham exposure. After exposure to 1000 micrograms/m3 of H2SO4, the six subjects not on routine medication exhibited a transient slowing of mucociliary clearance and also decrements in sGaw, FEV1/FVC, MMEF, and V25 (P less than 0.05) in both sets of measurements. The four asthmatics on daily medication exhibited stepwise mucociliary clearance that was too variable to allow detection of any H2SO4 effect on clearance. The 1000 micrograms/m3 of H2SO4 did produce decrements in V25 (P less than 0.05), but the variability of the other respiratory parameters in this small group was too great to permit detection of changes. Mucociliary clearance rates in both groups in the sham exposure tests were significantly slower than those of healthy nonsmokers studied previously using the same protocols. The extent of mucociliary clearance slowing following the 1000 micrograms/m3 exposure in the nonmedicated subjects was similar to that in the healthy nonsmokers. This similar change, from a reduced baseline rate of clearance, together with the significant change in respiratory function, indicate that asymptomatic asthmatics may respond to H2SO4 exposures with functional changes of greater potential health significance than do healthy nonsmokers.

Adult↗
PubMed1985

A variable feed rate mechanism for fluidized bed asbestos generators.

A simple and inexpensive dust feed mechanism has been designed for use with a two-phase fluidized bed generator (FBG). The mechanism is especially useful for generating asbestos aerosols, but may be used with other dusts as well. Using this system, a steady state concentration (39.1 fibers/cc greater than 5 microns in length +/- 6.2%) of asbestos aerosol was maintained in an inhalation chamber for five hours. In addition, FBG output concentration was easily adjusted and quickly equilibrated (within 10 minutes). The system provides a good technique for generating asbestos aerosols for day-long animal exposures.

Aerosols↗
PubMed1985

Collagenase in the lower respiratory tract of patients with adult respiratory distress syndrome.

Collagenase activity in the bronchoalveolar lavage (BAL) of patients with adult respiratory distress syndrome (ARDS) was measured against Type I collagen (17 patients) and against Type III collagen (13 patients). Serine protease activity was also measured against Type III collagen (13 patients). Type I collagenase activity was detectable in 12 of 17 and Type III collagenase was detectable in 12 of 13 patients with ARDS. The 10 control subjects had no detectable Types I or III collagenase activity. Total and differential white cell counts were analyzed in the lavage fluid. Although the total counts did not differ between patients with ARDS and control subjects, the percentage of neutrophils was increased more than 25-fold and the percentage of macrophages was reduced almost 10-fold in the ARDS patients. Serial collagenase activity was followed in 1 ARDS survivor. In this patient Type III collagenase activity peaked before the Type I collagenase activity or serine protease activity reached their maximums. Both the latter enzyme activities paralleled the total recoverable cells in the BAL.

Adult↗
PubMed1985

Utilization of a peroxidase antiperoxidase complex in an enzyme-linked immunosorbent assay of elastin-derived peptides in human plasma.

Chronic obstructive pulmonary disease (COPD), a major cause of morbidity and death in the smoking population, develops insidiously over many years, and significant impairment of lung function usually occurs before the disease is diagnosed. Because lung elastin degradation appears to be a prerequisite for the development of the disease, immunologic detection of elastin-derived peptides in the blood might be an effective approach to the early detection and monitoring of the disease. We here report an improved enzyme-linked immunosorbent assay for elastin peptides using a peroxidase-antiperoxidase complex as the reporter group. The assay is sensitive to 2 ng/ml elastin peptides. We show that for optimal, reproducible results the assay should be carried out at 16 degrees C rather than at room temperature and that determinations should be made on plasma containing protease inhibitors rather than on serum. The levels of elastin-derived peptides appeared to remain relatively constant when multiple samples were taken during a 5- to 10-wk period from individual subjects. In addition, patients with COPD had elevated elastin peptide levels (127 +/- 47 ng/ml) compared with levels in normal nonsmokers (58 +/- 17 ng/ml), whereas normal smokers had values intermediate between the 2 groups (mean peptide levels of 76 +/- 42 ng/ml). A small group of normal smokers (20%) had elevated elastin peptide levels similar to those in the emphysema group and may represent that group of smokers who are at risk of developing obstructive lung disease.

Animals↗
PubMed1985

Critical issues in air pollution epidemiology.

The epidemiological studies which have had significant impact on the setting of National Ambient Air Quality Standards (NAAQSs) were performed more than twenty years ago. Most of the more recent studies have been seriously flawed in their design and/or execution because they neglected to account for important variables such as: pollutant exposures other than those from ambient air; the influence of personal activity on pollutant uptake; host responsiveness; and the separate contributions of recent transient peak exposures and long-term chronic exposures on the effects endpoints. For particulate pollutants, the influence of composition and size distribution has also received too little consideration. In order to address these deficiencies, research and methods development are needed on: indices for particulate exposures; identification of exposures relevant to the effects; improved indices of effects; acquisition of response data; identification of exposed populations; and identification of susceptible subgroups. Approaches to these needs are discussed, along with brief reviews of several recent studies that have focused on critical issues of concern, made the necessary efforts to characterize the relevant exposures of the populations being studied, and demonstrated human responses to ambient pollutants at current exposure levels.

Adult↗
PubMed1985

Airborne acidity: estimates of exposure and human health effects.

Human health effects have resulted from the inhalation of ambient acidic aerosols, and there is suggestive evidence that current North American levels of exposure are producing excesses in respiratory morbidity. Annual mean mortality rates have been correlated with ambient aerosol concentration indices, with SO4(2-), FP, IP, and TSP having a descending order as predictive coefficients. These pollutant indices also contain H+ in descending mass ratios, and may all be surrogates for H+ as an active agent. Controlled exposure studies in humans and animals provide evidence that acidic aerosols produce greater changes in respiratory mechanical function and rates of particle clearance than other constituents of ambient particulate matter. The strong acid content of the ambient aerosol has not been measured in any of the population based pollutant effects studies in which it is a likely causal factor. The absence of direct measurement data on acidic aerosol in these studies, and their reliance on surrogate indices such as SO2 and SO4(2-), precludes firm conclusions about exposure-response relationships. High priority areas for further investigation include systematic investigation of the spatial and temporal distribution of population exposures; extension and refinement of population response studies in relation to acid aerosol exposures; responses of normal healthy and asthmatic human volunteers to mixtures of acidic aerosols and oxidant vapors under controlled conditions of exposure and exercise intensity; and progression of changes in lung epithelia during repetitive daily exposures of experimental animals to acidic aerosols, oxidants, and their mixtures, with concurrent measurements of particle clearance and respiratory function.

Acids↗
PubMed1985

Influence of airway and airspace sizes on particle deposition in excised donkey lungs.

Tests of aerosol deposition with breath holding and of lung function were performed on the excised lungs of three donkeys following regional in vivo radioaerosol deposition tests. Corrosion casts were made of the lungs to determine the dimensions of the tracheobronchial (TB) tree, and histological sections were taken to determine average alveolar airspace size. Static lung function tests, i.e., static compliance and specific compliance (Cstat and Cspec), agreed well with the predicted and reported in vivo values, as did the slope of Phase III from the single breath nitrogen washout (SBNW). Dynamic tests, i.e., dynamic compliance (Cdyn) and pulmonary resistance (Rpulm), displayed larger inter- and intra-subject variation, and showed poor agreement with reported in vivo values. Breathholding tests using 0.55 micron diameter aerosol indicated a mean respiratory airspace dimension of 0.16 mm, while the mean alveolar diameter from the lung sections was 0.19 mm. Breathholding tests with 1.18 micron aerosol indicated a mean small airway size of 0.65 mm, corresponding to the sizes of small airways on the corrosion casts. The donkeys have larger central airways but smaller peripheral airways than humans, and greater tracheobronchial deposition efficiency for 5 micron diameter particles. Tracheobronchial deposition in donkeys appears to be concentrated more distally than in humans, and may be related to the monopodal airway branching pattern in the former.

Aerosols↗
PubMed1984

Interspecies comparisons of particle deposition and mucociliary clearance in tracheobronchial airways.

Inhaled insoluble particles that deposit along normal healthy tracheobronchial airways of humans and other mammals are transported on the proximally moving mucous lining to the larynx, where they are swallowed. The transit time from the most distal ciliated airways varies from 0.1 to 1 d, with each individual having a relatively constant, characteristic time. The exact time course of clearance depends on the distributions of both particle deposition and mucus velocities along the airways. There are too few data on intrabronchial deposition and mucociliary transport rates for laboratory animals to permit a thorough intercomparison among species. However, enough is known about the relative lung sizes and anatomical differences among the various species to make some preliminary, but important, distinctions. As compared to commonly used experimental animals, humans have larger lungs and a more symmetric upper bronchial airway branching pattern. In addition, humans do considerable oral breathing, thus bypassing the effective air cleaning capability of the nasal airways. These differences contribute to a greater amount of upper bronchial airway particle deposition in humans, as well as to greater concentrations of deposition on localized surfaces near airway bifurcations. Airborne irritants that deposit in small ciliated airways may produce marked changes in mucociliary transport. Such materials include cigarette smoke, submicrometer-sized sulfuric acid mist, nitrogen dioxide, and ozone. For cigarette smoke and sulfuric acid, which have been studied for transient effects following single brief exposures in both humans and animals, the responses are similar. Upon repetitive exposures in animals, both of these irritants produce persistant alterations in clearance rates and airway morphometry. Studies of the effects of ozone on mucociliary clearance have, up to now, been limited to tests of the responses of rats to single exposures. The similarities between the known effects of various irritants suggests a nonspecific response.

Air Pollutants↗
PubMed1984

Bias in air sampling techniques used to measure inhalation exposure.

Factors have been evaluated which contribute to the lack of agreement between inhalation exposure estimates obtained by time-weighted averaging of samples taken with mini hi-volume samplers, and those measured by time integrating, low-volume, lapel mounted, personal monitors. Measurements made with real-time aerosol monitors on workers at a Be-Cu production furnace show that part of the discrepancy results from variability of the aerosol concentration within the breathing zone. Field studies of sampler inlet bias, the influences of the electrostatic fields around polystyrene filter holders, and resuspension of dust from work clothing, were done in three areas of a Be plant. No significant differences were found in Be air concentrations measured simultaneously by open and closed face cassettes, and "mini hi-volume" samplers mounted on a test stand. No significant influence on Be collection was detected between either positively or negatively charged monitors and charge neutralized control monitors. The effect of contaminated work clothing on dust collection by lapel mounted monitors is most important. Beryllium release from the fabrics affected air concentrations measured by fabric mounted monitors more than it affected concentrations measured by monitors positioned above the fabrics. The latter were placed 16 cm from the vertically mounted fabrics, to simulate the position of the nose or mouth. We conclude that dust resuspended from work clothing is the major source of the observed discrepancy between exposures estimated from lapel mounted samplers and time-weighted averages.

Aerosols↗
PubMed1984

Dose-dependent effects of submicrometer sulfuric acid aerosol on particle clearance from ciliated human lung airways.

We previously showed that 1 hr exposures to submicrometer sulfuric acid (H2SO4) aerosol at 100 and 1000 micrograms/m3 altered the bronchial mucociliary clearance of monodisperse 7.6 micron MMAD 99mTc-labelled ferric oxide (Fe2O3) in healthy, nonsmoking humans. The 7.6 micron particles were primarily deposited in the larger bronchial airways, where submicrometer H2SO4 has very little deposition. To determine the extent that submicrometer H2SO4 aerosol affects clearance from the more distal ciliated airways, we measured the clearance of a monodisperse 4.2 micron MMAD Fe2O3 aerosol in eight other healthy nonsmoking subjects. A greater fraction of 4.2 micron particles deposited in distal conductive airways. Bronchial mucociliary clearance was slower following 1 h nasal H2SO4 inhalations at 100, 300 and 1000 micrograms/m3 than after sham exposures, while mucociliary transport rates within the trachea and indices of respiratory mechanics were unchanged. A comparison of the effects of 1 h exposures at 100 micrograms/m3 on the clearance of 7.6 and 4.2 micron particles suggests greater physiological response in distal ciliated airways than in larger central airways.

Adult↗
PubMed1984

Proteinase inhibitory function in inflammatory lung disease. I. Acute bacterial pneumonia.

This study examines the bronchial alveolar lavage (BAL) samples from a group of patients with acute bacterial pneumonia (n = 13) and makes a comparison with a control group (n = 5). The proteinase inhibitory capacity was examined and found to be composed primarily of alpha 1-proteinase inhibitor (PI, alpha 1-antitrypsin) and, to a lesser extent, bronchial mucosal inhibitor. Although the average PI concentration was elevated approximately 5-fold in the pneumonia group, its inhibitory function against elastase was decreased 15-fold when compared with that in the control group. The pneumonia group showed an increased concentration of immunologically identified elastin-derived peptides. Some of the BAL fluid from patients with pneumonia showed elastolytic activity against amorphous insoluble lung elastin. The majority of the elastase appears to be of neutrophil origin. Bronchial mucosal inhibitor is shown to be a component of both normal and pneumonia BAL fluids by both immunologic quantitation and by its resistance to perchloric acid inactivation. Compared with those from control subjects, BAL samples from patients with acute bacterial pneumonia showed a decreased proteinase inhibitor function and both increased elastolytic activity and elastin-derived peptide concentration.

Acute Disease↗
PubMed1984

Depression of lymphocyte traffic in sheep by induced systemic arterial hypotension and by acute arterial occlusion.

Shock and arterial insufficiency have been observed to be associated with increased levels of sepsis and mortality. As the vast majority of small recirculating lymphocytes reach lymph nodes in arterial blood, the haemodynamic components of lymph node function would appear to be of importance. Lymphocyte traffic in sheep, as mirrored by the output of lymphocytes into the efferent lymph of popliteal lymph nodes, obtained by chronic cannulation of efferent lymphatics, was found to be sharply depressed both by intravenous nitroprusside infusion induced systemic arterial hypotension and by acute femoral arterial ligation on the side of the study node. In the nitroprusside infusion induced arterial hypotension studies, the depressions in lymphocyte traffic were closely related to the depressions in systemic arterial blood pressure. Excellent colateral circulation and compensatory physiological mechanisms in the sheep limited the duration of these depressions in lymphocyte traffic.

Animals↗
PubMed1983

Monitoring real-time aerosol distribution in the breathing zone.

A prototype air sampling, data recording, and data retrieval system was developed for monitoring aerosol concentrations in a worker's breathing zone. Three continuous-reading, light-scattering aerosol monitors and a tape recorder were incorporated into a specially designed and fabricated backpack for detailed field monitoring of both temporal and spatial variability in aerosol concentrations within the breathing zone. The backpack was worn by workers in a beryllium refinery. The aerosol which passed through each monitor was collected on a back-up filter for later chemical analysis for Be and Cu. The aerosol concentrations were recorded on magnetic tape as a function of time. The recorded signals were subsequently transcribed onto a strip chart recorder, then evaluated using a microcomputer with graphics capability. Field measurements made of the aerosol concentration at the forehead, nose, and lapel of operators during the melting and casting of beryllium-copper alloy demonstrated that there is considerable variability in concentration at different locations within the breathing zone. They also showed that operations resulting in worker exposure can be identified, and the precise time and duration of exposure can be determined.

Aerosols↗
PubMed1983

Sequential cardiorespiratory patterns of anesthetic induction with ketamine in critically ill patients.

Hemodynamic and O2 transport effects of ketamine anesthesia were evaluated in 22 critically ill patients. After placement of radial and pulmonary artery catheters, simultaneous measurement were made of cardiac output, intravascular pressures, arterial and mixed venous gases, saturations, pH, and Hct; cardiorespiratory values then were calculated for a preinduction control period and sequentially at frequent intervals over a 15-min observation period. In general, there was an early progressive increase in HR, cardiac index (CI), arterial and venous pressures, stroke work, and O2 delivery (DO2); O2 consumption (VO2) and O2 extraction (O2 Ext) decreased. In general, ketamine produced an inotropic cardiac response, but these responses were not uniform; a relatively small percentage had reduced pressures, flow, and reduced myocardial performance that were related to hypovolemia and associated medical conditions.

Anesthesia↗
PubMed1983

Immunologic measurement of elastin-derived peptides in human serum.

Chronic obstructive pulmonary disease (COPD), a major cause of morbidity and death in the smoking population, develops insidiously over many years, and usually significant impairment of lung function has occurred before the disease is diagnosed. It is likely that destruction of the elastic fiber is a prerequisite for the development of the disease, and it is possible that immunologic identification in the serum of peptides derived from lung elastin degradation might be an effective approach to the early detection and monitoring of the disease. We prepared antibodies to peptides derived from human lung parenchymal elastin and used these antibodies in an enzyme-linked immunosorbant assay to quantitate elastin-derived peptides in the serum of 39 normal control nonsmokers, 33 smokers with normal lung function, and 40 patients with COPD. On average, statistically significant higher levels of elastin-derived peptides were found in the normal smokers and COPD patients compared to the controls. Further work with larger numbers of subjects is necessary to determine whether such a test is effective in identifying those individuals who are at risk of developing COPD.

Antibodies↗
PubMed1983

The risk factors, incidence, and prognosis of ARDS following septicemia.

Adult respiratory distress syndrome (ARDS) is frequently associated with septicemia. However, the incidence, risk factors, and prognosis are poorly defined. Therefore, during a nine-month period, 116 consecutive patients with septicemia were analyzed. ARDS occurred in 21 of 116 (18 percent) of septicemic patients. Shock preceded all cases of ARDS but occurred in only 15 percent of patients without ARDS (p less than 0.001). Thrombocytopenia was more frequent (62 percent vs 16 percent, p less than 0.001). Age, sex, compromised host status, type of septicemia, temperature, and white blood cell count were not significantly different between the two groups. It is concluded that ARDS frequently complicates all forms of septicemia. It is usually preceded by shock and thrombocytopenia and significantly worsens the prognosis.

Aged↗