In vitro response of human pulmonary macrophages with volcanic ash: a morphological study.
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Biomedical subjects
Publications and source records attributed to R R Martin.
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In this investigation, 10 adult stutterers were given time-out contingent on each stuttering. Ten other stutterers administered themselves time-out contingent on each stuttering. Stutterers in both time-out conditions evidenced marked reductions in stuttering compared with spontaneous speaking base rates. Stutterers who presented their own time-outs for stuttering, however, showed significantly less extinction of reduced stuttering following the time-out period, and significantly greater generalization to a telephone speaking situation, than did stutterers who were given time-out by an experimenter.
Cefamandole resistance in five patients was studied. Microorganisms emerged resistant to cefamandole during therapy with the drug in three patients with complicated infections. This resistance was associated with an enhanced production of beta-lactamase and/or with a change in the substrates and the isoelectric focusing patterns of the enzymes. Cross-resistance to other beta-lactam antibiotics developed concurrently in isolates from these patients. Disk diffusion tests did not detect resistance to cefamandole in the pretreatment isolate from the fourth patient; this isolate produced inactivating enzymes, and resistance was detected only in broth dilution tests. In the fifth patient, infection with a cefamandole-resistant Enterobacter developed during postoperative therapy with the drug. Resistance to cefamandole in the isolate from this patient was unstable and was associated with inducible beta-lactamase activity. These examples emphasize the need for close monitoring of patients who are given cefamandole and for thorough in vitro evaluation of isolates from the patients both before and after treatment.
Cefonicid (Smith Kline & French Laboratories; D-75073) is a new parenteral cephalosporin with a markedly long half-life, high serum levels, and good in vitro activity against Haemophilus influenzae. Patients with community-acquired pneumonia were randomized 2:1 to receive cefonicid, 1 g daily (21 cases) or cefamandole, 1 g every 6 h (12 cases). The two groups were similar, except that the cefonicid patients were older (mean 42 versus 31 years). Peak serum levels of cefonicid averaged 133 microgram/ml after intravenous and 83 microgram/ml after intramuscular administration compared with 55 microgram/ml with intravenous cefamandole. All 9 patients on intramuscular cefonicid and 8 or 12 patients on intravenous cefonicid had trough serum levels of greater than 2.0 microgram/ml at 24 h. Sputum levels of cefonicid were usually between 2.0 and 4.0 microgram/ml and did not correlate with serum levels. Cefonicid was well tolerated, and all cefonicid patients responded clinically. Sputum cultures for H. influenzae or Streptococcus pneumoniae became negative in 6 of 7 cefamandole patients and 13 or 15 cefonicid patients. In in vitro studies, cefonicid inhibited 90% of beta-lactamase-negative h. influenzae at 0.5 microgram/ml and beta-lactamase-positive strains at 2.0 microgram/ml. Cefonicid inhibited 50% of S. pneumoniae at 1.6 microgram/ml, but required 6.4 microgram/ml to inhibit 90%. Cefonicid once a day appears to be as safe and as effective as cefamandole four times a day for therapy of community-acquired pneumonia.
The nonadrenergic inhibition of airway smooth muscle was investigated in vivo in the anesthetized cat. We examined 1) the bronchodilatating nature of the selective purinergic agonists [adenosine (AD) and adenosine triphosphate (ATP)], 2) antagonistic nature of aminophylline and quinidine, and 3) the comparative efficacy of nonadrenergic and sympathetic inhibition in reversing bronchoconstriction induced with serotonin. Alterations in smooth muscle tone were studied via electrical stimulation of the vagus nerves and measurements of pulmonary resistance. We found that neither AD nor ATP, aerosolized or injected, altered the tonic bronchoconstriction. Dipyridamole, an AD reuptake inhibitor, did not alter the response to AD, ATP, or electrical stimulation. Both aminophylline and quinidine block nonadrenergic dilatation at high dose levels (69 and 29 mg/kg, respectively); further, both reputed antagonists impair cholinergic excitation. Nonadrenergic inhibition is equipotent to sympathetic inhibition in reversing bronchoconstriction; however, nonadrenergic inhibition is more prolonged (4.0 +/- 1.8 min). We conclude that probably neither ATP nor AD is the neurotransmitter for nonadrenergic bronchodilatation in the cat, and that nonadrenergic inhibition is both potent and long lasting.
Methacholine inhalation challenges were performed in 10 young smokers who denied having respiratory symptoms and in 10 nonsmokers of the same age. There were five males and five females in each group. The bronchoconstriction was evaluated with specific lung conductance (sGL), maximum partial (initiated from end-inspiratory lung volume) expiratory flows assessed at 40% vital capacity breathing air (Vmax40p air), and a He-O2 mixture (Vmax40p He), and with maximum complete flows breathing He-O2 [forced expiratory volume at 1 s (FEV1), Vmax50c He]. Dose-response curves were studied for 1) threshold concentration (TC) where values depart by more than two SD from base line; 2) provocative concentration (PC) causing a fixed fall in a parameter. Smokers differed significantly from nonsmokers for TC and PC accessed by Vmax40p He (P less than 0.001 and P less than 0.01, respectively), Vmax40p air (P less than 0.01), and Vmax50c He (P less than 0.01 and P less than 0.05, respectively). TC and PC estimated by sGL and FEV1 were not significantly different. Males and females showed a similar reaction.
The regional distribution of a bolus of gas inhaled at residual volume (RV) is attributed to regional airway closure and is responsible for the phase IV of the single-breath washout during the following deflation. As bronchospasm increases the range of airway opening pressures through the lung, the regional distribution of the bolus could change with effects on the shape of the single-breath washout. We investigated the regional distribution of boluses inhaled at RV and their single-breath washouts during methacholine-induced bronchospasm in prone dogs. With increasing total lung resistance (RL) we first observed in five out of eight animals a preferential "redistribution" of the bolus to the upper caudal regions of the lung, which could be partially attributed to the increased lung volume at RV. When maximal RL was attained, the bolus was evenly distributed through all regions of the lung in these animals with disappearance of phase IV and increased slope of phase III, and a final decrease of tracer concentration at low lung volumes was observed. We conclude from these data that increased bronchomotor tone in dogs results in a less homogeneous intraregional distribution of the bolus with increased slope of phase III and in a more even interregional distribution leading to disappearance of phase IV. In severe bronchospasm the downward slope at low lung volume suggests intraregional closed lung units emptying through collateral pathways into still open neighboring units.
The effects of human bronchoalveolar cells on pokeweed-mitogen-induced immunoglobulin(Ig) secretion in vitro were investigated, using a reverse hemolytic plaque assay. Unfractionated peripheral blood mononuclear cells from 7 nonsmoking normal subjects responded to pokeweed mitogen with a geometric mean of 6,550 Ig-secreting cells per million cultured mononuclear cells, whereas monocyte-depleted mononuclear cells responded with only 148 (p = 0.015, paired 2-tailed t test). The addition of 1 to 20% autologous bronchoalveolar cells to unfractionated mononuclear cells progressively suppressed the Ig-secretory response (p less than 0.01, paired t test comparing 0 to greater than or equal to 10% added bronchoalveolar cells). However, the addition of low concentrations of bronchoalveolar cells to monocyte-depleted mononuclear cells partially reconstituted the response to pokeweed mitogen, whereas the response with higher concentrations of bronchoalveolar cells was similar to background responses. Thus bronchoalveolar cells could modulate pokeweed-nitrogen-induced Ig secretion in different ways, depending on the pressure or absence of monocytes in the mononuclear cell population. The suppressor activities of bronchoalveolar cells were not abrogated by prior irradiation and were only partially reversed by the addition of indomethacin to the cultures. However, prior disruption of bronchoalveolar cells completely abolished their suppressive functions. Suppression of pokeweed-mitogen-induced Ig secretion is probably mediated by intact, radioresistant pulmonary alveolar macrophages.
On quantitative cultures using media selective for staphylococci, 15 of 145 healthy women (10.3%) had Staphylococcus aureus isolated from the vagina; numbers of staphylococci ranged from 3 x 10(1) to 7.3 x 10(7) per swab. Nine of 15 women who were S. aureus vaginal carriers were also nasal carriers, but only 30 of 130 of women without vaginal S. aureus also had coagulase-positive staphylococci in the nose (p = 0.002). Among women with S. aureus at both sites, the numbers of vaginal and nasal staphylococci isolated were not correlated. No association was found between the presence of vaginal staphylococcal colonization and the use of tampons compared to napkins. Cultures taken during menstruation from which S. aureus were isolated contained significantly higher numbers of coagulase-positive staphylococci (mean log +/- SE of 4.0 +/- 0.3) than positive cultures after menstruation (3.3 +/- 0.2) (p less than 0.02).
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Aryl hydrocarbon hydroxylase was measured in cultured human lymphocytes induced with benzathracene and in pulmonary alveolar macrophages induced in situ in cigarette smokers. Considered separately, neither lymphocyte AHH nor macrophage AHH levels were distinctly different in either noncancer or lung cancer patients. Considered simultaneously, lymphocyte and macrophage AHH levels are quite different in noncancer and lung cancer patients. The lung cancer patient group was seen to contain a significantly higher percentage of persons with high levels of AHH than did an age-matched group of noncancer patients, (P less than 0.001), when more than one tissue was assayed to determine the individual's enzyme levels.
Neutrophil function was investigated in a male child with glycogenosis type Ib who demonstrated susceptibility to staphylococcal infections and neutropenia. Random motility and directed migration of the patient's neutrophils in vitro were profoundly diminished. The patient's neutrophils stimulated in suspension with chemotactic factors (CFs) generated chemiluminescence that was comparable to or greater than that generated by neutrophils from controls, but the patient's neutrophils failed to assume a normal bipolar configuration in response to chemotactic stimuli. They also failed to demonstrate enhanced adherence after a single exposure to CFs or decreased adherence after sequential exposures to increasing concentrations of CFs. Unlike neutrophils from controls, the patient's neutrophils failed to redistribute surface adhesion sites from lamellipodia (anterior pole) to uropods (tail) after sequential CF stimuli. These findings indicate a functional link between CF-induced configurational changes and altered adhesiveness of neutrophils under conditions of directed locomotion and suggest that a redistribution of surface adhesion sites is related to the mechanism of neutrophil locomotion.
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Ceforanide is a new (parenteral) long-acting cephalosporin with antimicrobial activity comparable to those of other second-generation cephalosporins. In a randomized prospective study, patients with community-acquired bacterial pneumonia were treated with ceforanide at 0.5 g every 12 h (28 cases) or with cefazolin at 1.0 g every 8 h (26 cases). The study groups were comparable in clinical and laboratory findings, including etiological diagnosis. Streptococcus pneumoniae was isolated from the sputum of 38 patients, of whom 8 (21%) were bacteremic. Mean peak and trough serum levels of ceforanide drawn 1 and 11.5 h after the 0.5-g intravenous dose were 39.6 and 2.5 microgram/ml, respectively. Of the 50 patients evaluable for efficacy, all responded clinically with no serious adverse reactions. In spite of clinical improvement and in vitro susceptibility, Haemophilus influenzae persisted in the sputum of five of the eight cefazolin-treated patients and four of the five patients treated with ceforanide. Ceforanide appears to be as safe and effective as cefazolin for the therapy of pneumonia caused by S. pneumoniae or H. influenzae, but neither drug was effective in clearing H. influenzae from the sputum.
Hfr strains of Escherichia coli were obtained by integrative suppression of a dnaA(Ts) mutation by the Inc P-1 plasmid RP1 without prior creation of an unnatural homology between the plasmid and the E. coli chromosome. Unmodified RP1 mobilized the polarized transfer of the chromosome in a counterclock-wise direction from a distinct origin between 81 min (pyrE) and 82 min (dnaA) with pyrE as a leading marker. Inheritance of RP1-Hfr chromosomal and antibiotic resistance genes was due to recombination with the recipient chromosome, as shown by the need for a functional recA system. The acquisition of temperature resistance and donor ability was accompanied by the disappearance of free plasmid when the selection pressure for integration was maintained (growth at 41 degrees C); the loss of temperature resistance and donor ability was accompanied by the reappearance of autonomous RP1 when the selection pressure was removed (growth at 30 degrees C).
The effect of experimental pulmonary air embolism on pulmonary perfusion was studied in 14 closed-chest, anesthetized, paralyzed dogs. During constant-rate air infusion through a femoral vein, regional distribution of lung perfusion was measured with radioactive xenon boluses injected via a catheter positioned distally to the pulmonary valve. The results obtained from nine prone dogs indicate a large shift of blood perfusion toward the dependent areas of the lung during air embolism; the results obtained in five supine dogs were similar but statistically less significant. Concomitant with the perfusion shift, pulmonary arterial pressure increased, more acutely during the first 30 min. Switching from air to N2O-O2 ventilation accentuated the perfusion shift, which may be reverted towards control values by intravenous administration of 0.4 mg of isoproterenol. Other alterations observed included moderate increase of pulmonary resistance and decrease of cardiac output. It is concluded, based on these results and an adjunct model study, that the observed changes were predominantly due to aggregation of air bubbles in the upper part of the pulmonary vasculature.
By use of 133Xe, the regional distribution of residual volume (RV) was measured in six seated healthy men, following a fast vital capacity (VC) expiration a) without and b) with a breath hold at residual volume of approximately 30 s and c) following a slow (greater than 30 s) VC expiration from total lung capacity (TLC) without a breath hold at RV. After the breath hold at RV, regional RV/TLC in the lower lung zones decreased significantly compared wih results obtained with fast expiratory VC and no breath hold at RV. At lung top the opposite was true. The distribution of regional RV/TLC was the same following the slow VC expiration with no breath hold at RV as with the fast expiration with the breath hold at RV. The different regional distribution of RV in b and c relative to a was probably due mainly to collateral ventilation, i.e., during the breath hold at RV and the slow expiration some of the gas that was trapped in the dependent lung zones behind closed airways escaped into the upper regions of the lung where the small airways had remained patent, leading to increased expansion of upper alveoli.
To elucidate the hydrodynamic events during pulmonary air embolism, experiments were conducted in a branching-tube apparatus and in small vessels. It was found that, as long as there existed an elevation differential between the two branches of a bifurcation, the vast majority of air bubbles always entered the higher branch. This finding is explained in terms of buoyancy, shear forces, and liquid flow velocity and is consistent with the in vivo finding of increased blood perfusion in the dependent lung regions during air embolization (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 51: 211-217, 1981). The pressures required to drive air bubbles through various small vessels were determined using three aqueous solutions of different surface tensions. Based on these measurements and a theoretical analysis, the diameter of air bubbles that could not pass through the pulmonary vessels was calculated to be 20-30 micrometers, agreeing well with a recent in vivo measurement (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 47: 537-543, 1979).