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Biomedical subjects

M Lippmann

Publications and source records attributed to M Lippmann.

At least 109 records · Page 6Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Treatment of mixed-dust pneumoconiosis with whole lung lavage.

A patient with silicosis and progressive dyspnea on exertion is described in whom open lung biopsy revealed active chronic inflammation with many macrophages filling alveolar spaces. Because of the extensive involvement by the disease of small air spaces, bilateral whole lung lavage was performed. The lung lavage effluent was striking in its blackish brown color. It was composed predominantly of macrophages containing silica, silicates, and graphite. Particles in the tissue and lavage were analyzed using scanning electron microscopy and energy dispersive X-ray analysis. The dry weight of the material removed was approximately 25 g, of which an estimated 135 mg was silica. The procedure resulted in immediate symptomatic improvement in the patient. Although his pulmonary function did not change significantly, it is hoped that removal of this material will improve his long-term prognosis.

Biopsy↗

Neuromuscular blocking effects of tobramycin, gentamicin, and cefazolin.

Forty patients (A.S.A. class I or II), 18 to 75 years of age, who were undergoing elective surgery were studied to determine the clinical and subclinical neuromuscular blocking effects of two antibiotics, tobramycin and gentamicin and to compare these effects with those produced by cefazolin, an aminoglycoside not known to produce paralysis. Patients were prospectively and randomly assigned in approximately equal numbers to one of four groups: group A received 1 mg/kg of tobramycin; group B, 1 mg/kg of gentamicin; group C, 500 mg of cefazolin; or group D, control (no antibiotic). Antibiotics were administered intravenously 45 minutes immediately preceding the study. The ulnar nerve was stimulated supramaximally and neuromuscular function was measured electromyographically. Anesthesia was induced with thiopental, 4 mg/kg IV, and maintained with endotracheal enflurane 1.0% to 1.5% (inspired) and N2O-O2 (2 L:1 L) after intubation. Succinylcholine (1 mg/kg) was administered after induction of anesthesia and the magnitude and duration of neuromuscular block monitored. d-Tubocurarine (0.1 mg/kg) was given 5 to 10 minutes after full recovery from succinylcholine and repeated as required. At the end of the operation, atropine, 0.02 mg/kg, and neostigmine, 0.4 mg/kg, were used to reverse the block. Base line neuromuscular data, duration of block of succinylcholine, and potency, duration of block, recovery rate, train-of-four fade, tetanic trend, response to double stimuli, post-tetanic effect, and reversibility of the subsequent d--tubocurarine-induced neuromuscular block were not significantly different (p less than 0.01) between any two groups. Tobramycin, gentamicin, and cefazolin, in recommended single doses, lack clinical neuromuscular blocking and subclinical relaxant-potentiating effects.

Adolescent↗

Elastolytic activity in pulmonary lavage fluid from patients with adult respiratory-distress syndrome.

To test the hypothesis that adult respiratory-distress syndrome (ARDS) is related to increased activity of the proteolytic enzyme elastase released from neutrophils in the lung, we determined the differential white-cell count, the elastolytic activity, the source of elastase, and the concentration and activity of the endogenous protease inhibitor alpha-1-antiprotease (alpha-1-AP) in bronchoalveolar lavage fluid from 23 patients with ARDS and from 55 patients without this syndrome. Neutrophil predominance (> 80 per cent) was observed in 18 of 23 patients with ARDS. High elastolytic activity of neutrophil origin was found in 12 of 23 patients with ARDS (52 per cent), in none of 16 normal nonsmokers (P < 0.01), in two of 17 normal smokers, and in three of 22 patients with chronic obstructive pulmonary disease. Although there were no significant differences in alpha-1-AP concentrations, its activity was reduced in eight of nine patients with ARDS and high elastolytic activity. We conclude that in many patients with ARDS, high levels of neutrophil elastolytic activity in the lungs are associated with reduced alpha-1-AP function.

Aged↗