Search PubMed⌕ Search

Biomedical subjects

T R Martin

Publications and source records attributed to T R Martin.

At least 127 records · Page 7Linked to original sources
PubMed1989

An evaluation of the toxicity of carbon fiber composites for lung cells in vitro and in vivo.

Carbon fiber composite materials are used in a variety of applications in industries, and machining processes often generate aerosols of these materials in the workplace. Because the potential health effects of these particles are uncertain, we evaluated the toxicity of a series of carbon fiber composites in vitro using rabbit alveolar macrophages and in vivo using direct intratracheal injection into rat lungs. For comparison, we studied two reference materials, Al2O3 and alpha-quartz, which are inert and toxic, respectively. We measured cytotoxicity in vitro for rabbit alveolar macrophages by trypan blue exclusion and by the release of 51Cr from prelabeled macrophages. We also injected the samples intratracheally into specific pathogen-free rats and 1 month later lavaged the lungs to recover airway cells and fluid. In each of the assays, the quartz was the most toxic substance tested, causing marked cytotoxicity for alveolar macrophages and large increases in airway cells and neutrophils in the rat lungs, whereas the Al2O3 was consistently the least toxic. Three of the composite samples consistently showed little toxicity, whereas two were consistently toxic for alveolar macrophages and caused significant accumulations of airway cells and neutrophils in the rat lungs. The results of the in vitro and in vivo studies produced a similar ranking of toxicity for all of the samples. These studies show that in vitro and in vivo testing is a useful approach to the evaluation of the potential biologic effects of new materials in the lungs. Although these carbon fiber composites appear to be much less toxic than quartz, the data suggest that two of the composites are not inert. Exposure limits more strict than those for nuisance dusts should be used in the workplace for these two composites. Longer term inhalation exposure studies using these two composites are warranted in order to better define their effects in the lungs.

Animals↗
PubMed1989

Response of the rat lung to respirable fractions of composite fiber-epoxy dusts.

It is unknown whether respirable dusts derived from the machining of composite fiber-epoxy materials pose a health risk. To evaluate the potential pulmonary toxicity of these materials, we studied the effects of six samples of dusts previously well characterized physically, chemically, and morphologically in the lungs of specific pathogen-free rats. A single intratracheal bolus of 5 mg of each sample was injected into separate groups of five rats each. For comparison, free crystalline silica (quartz) and aluminum oxide were used as positive and negative controls in additional animals. One month later, the lungs were fixed and sectioned for light microscopy. Histopathology scores for the six composite-epoxy samples showed a continuum of lung injury that was between the negative and positive controls. None of the composite dusts had effects that paralleled those of quartz; however, four of the composite dusts produced reactions that were more severe than that seen with aluminum oxide. Therefore, respirable fractions of some types of composite materials can induce pathological changes in lungs of experimental animals. The features responsible for the variation in host response between samples are, as yet, unclear.

Animals↗
PubMed1989

Impaired clearance of aerosolized Legionella pneumophila in corticosteroid-treated rats: a model of Legionnaires' disease in the compromised host.

To develop a model of legionnaires' disease in a host with defective cell-mediated immunity, rats were treated with subcutaneous cortisone acetate and exposed to aerosolized Legionella pneumophila. Bacterial clearance, histopathology, cell recovery by bronchoalveolar lavage, serology, and splenocyte blastogenesis to heat-killed L. pneumophila were studied in cortisone-treated rats and normal controls. Corticosteroid administration resulted in a dosage-related defect in the clearance of L. pneumophila. Cortisone-treated animals had a diffuse, progressive pneumonitis, but the influx of neutrophils to the lung, the serum antibody response, and the sensitization of splenocytes to L. pneumophila were not impaired by corticosteroids. The marked lymphocyte depletion observed in cortisone-treated animals may have contributed to defective expression of cell-mediated immunity. This model may be useful in further studies of the pathogenesis and treatment of legionellosis in the compromised host.

Aerosols↗
PubMed1989

Use and misuse of metered-dose inhalers by patients with chronic lung disease. A controlled, randomized trial of two instruction methods.

Metered-dose inhalers are often used incorrectly by patients with chronic airflow obstruction, and there is a lack of controlled studies designed to evaluate methods to teach the correct use of these devices. Therefore, we screened 100 consecutive stable outpatients for correct or incorrect inhaler use and then conducted a randomized trial of two methods to teach correct use. Patients were classified as correct or incorrect users with a modified metered-dose inhaler containing a thermistor that detected inspiration, inhaler activation, and the duration of breath-holding. Patients were classified as incorrect users if they failed to: (1) activate the inhaler once during inspiration, and/or (2) hold their breath at the end of inspiration. There were 38 correct users and 62 incorrect users. Incorrect users were randomized to one of two teaching protocols: (1) standardized verbal instruction alone, or (2) standardized verbal instruction plus an automatic visual signal during inspiration. Incorrect users were restudied 6 to 10 wk later to reassess technique. Both treatment protocols were equally effective in converting incorrect user. However, the verbal instruction alone required significantly less time than the instruction with the mechanical aid. For all subjects, the proportion using correct technique declined over time, particularly for incorrect users. We also examined a series of patient characteristics, obtained by questionnaire and spirometry, to determine whether they could be used in the clinical setting to identify incorrect users. By discriminant analysis, a group of four variables predicted correct metered-dose inhaler use: bronchodilator responsiveness, a history of additional about proper technique, verbal knowledge of the correct inhaler maneuvers, and the patient's perception of whether it is important to use an inhaler.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Role of mast cells in anaphylaxis. Evidence for the importance of mast cells in the cardiopulmonary alterations and death induced by anti-IgE in mice.

We used genetically mast cell-deficient WBB6F1-W/Wv and WCB6F1-S1/S1d mice and the congenic normal (+/+) mice to investigate the effects of intravenous infusion of goat antimouse IgE on heart rate (HR), pulmonary dynamic compliance (Cdyn), pulmonary conductance (GL), and survival. In WBB6F1-+/+ and WCB6F1-+/+ mice, anti-IgE induced extensive degranulation of tracheobronchial mast cells, as well as significant elevation of HR, significant reductions in Cdyn and GL and, in some cases, death. In contrast, W/Wv and S1/S1d mice exhibited little or no pathophysiological responses and no mortality after challenge with anti-IgE. In W/Wv mice reconstituted with mast cells by intravenous administration of bone marrow cells derived from congenic +/+ mice (+/+ BM----W/Wv mice), anti-IgE induced extensive mast cell degranulation, as well as pathophysiological responses and mortality similar to those observed in WBB6F1-+/+ mice. These findings suggest a critical role for mast cells in the development of the cardiopulmonary changes and mortality associated with anti-IgE-induced anaphylaxis.

Anaphylaxis↗
PubMed1989

Local abnormalities in coagulation and fibrinolytic pathways predispose to alveolar fibrin deposition in the adult respiratory distress syndrome.

To determine the possible mechanism(s) promoting alveolar fibrin deposition in the adult respiratory distress syndrome (ARDS), we investigated the initiation and regulation of both fibrinolysis and coagulation from patients with ARDS (n = 14), at risk for ARDS (n = 5), and with interstitial lung diseases (ILD) (n = 8), and normal healthy individuals (n = 13). Bronchoalveolar lavage (BAL) extrinsic pathway inhibitor activity was increased in ARDS BAL compared with patients at risk for ARDS (P = 0.0146) or normal controls (P = 0.0013) but tissue factor-factor VII procoagulant activity was significantly increased in ARDS BAL compared with all other groups (P less than 0.001). Fibrinolytic activity was not detectable in BAL of 10 of the 14 patients with ARDS and low levels of activity were found in BAL of the other four ARDS patients. Depressed fibrinolysis in ARDS BAL was not due to local insufficiency of plasminogen; rather, there was inhibition of both plasmin and plasminogen activator. Plasminogen activator inhibitor 1 was variably detected and low levels of plasminogen activator inhibitor 2 were found in two ARDS BAL samples, but plasminogen activator inhibitor 2 was otherwise undetectable. ARDS BAL antiplasmin activity was, in part, due to alpha 2-antiplasmin. We conclude that abnormalities that result in enhanced coagulation and depressed fibrinolysis, thereby predisposing to alveolar fibrin deposition, occur in the alveolar lining fluids from patients with ARDS.

Adult↗
PubMed1989

Effects of leukotriene B4 in the human lung. Recruitment of neutrophils into the alveolar spaces without a change in protein permeability.

Leukotriene B4 (LTB4) is a major product of human alveolar macrophages and has potent chemotactic activity for neutrophils (PMN) in vitro. To evaluate the effects of LTB4 in the normal human lung, we instilled LTB4 (5 X 10(-7)M, 10 ml) into a subsegment of the right middle lobe and 0.9% NaCl (10 ml) into a subsegment of the lingula using a fiberoptic bronchoscope in 12 healthy human volunteers. 4 h later, we performed bronchoalveolar lavage of the same subsegments. Compared with the NaCl instillation, LTB4 caused a large increase in lavage total cells (NaCl = 6.8 +/- 1.0 X 10(6) vs. LTB4 = 26.4 +/- 5.0 X 10(6), P less than 0.01), most of which were PMN (NaCl = 12.2 +/- 4.6% vs. LTB4 = 55.7 +/- 6.0%, P less than 0.001). In contrast, there was only a small increase in lavage total protein, and the lavage total protein correlated weakly with lavage total cells and PMN. The production of superoxide anion by the lavage PMN in response to phorbol myristate acetate was similar to that of peripheral blood PMN. The migration of lavage PMN was normal toward the chemotactic peptide FMLP, but reduced toward LTB4 and zymosan-activated human serum. Morphometric analysis using transmission electron microscopy indicated a selective loss of small granules in the lung neutrophils as compared with peripheral blood neutrophils. The data indicate that in the normal human lung, LTB4 can recruit active PMN into the airspaces without causing a significant change in the protein permeability of the epithelial barrier.

Adult↗
PubMed1989

Bronchoalveolar lavage desmosine in bleomycin-induced lung injury in marmosets and patients with adult respiratory distress syndrome.

Measurement of urinary desmosine in experimental models of emphysema has been used to demonstrate elastin catabolism. In order to evaluate the hypothesis that accelerated elastin degradation also occurs in association with acute lung injury characterized by fibrotic repair, we prepared acid hydrolysates of lung lavage (LL) and used a radioimmunoassay for desmosine to measure concentrations of this elastic-specific cross-link in LL. Lavage desmosine (pmol/100 microliter LL) was measured following bleomycin-induced lung injury in marmosets and was shown to be elevated at 1 week (median 6.0, range 5.1-7.8), 2 weeks (8.4, 6.2-8.7), and 4 weeks (7.6, 4.8-7.8) compared to control levels (1.8, 1.4-3.7). Elevations of lavage desmosine after bleomycin were temporarily associated with remodeling of the lung as indicated by increased total lung collagen, reduced diffusing capacity and lung compliance, and histologic evidence of pulmonary fibrosis. Bronchoalveolar lavage (BAL) desmosine was measured in patients with the Adult Respiratory Distress Syndrome (ARDS) and compared with patients at risk, patients with other interstitial lung diseases, and normal healthy controls. BAL desmosine (pmol/100 microliters) was not significantly different in patients with ARDS (3.2, 2.1-3.0), patients at risk for ARDS (2.8, 2.5-4.4), and those with interstitial lung disease (3.0, 1.7-5.3) compared to normal controls (2.9, 1.9-4.7). There were poor correlations of BAL desmosine with physiologic indices of severity of disease in patients with ARDS and those at risk. Accelerated elastolysis occurred in the lower respiratory tract during the evaluation of bleomycin-induced pulmonary fibrosis in marmosets but was undetectable in BAL of patients studied within the first 3 days of ARDS.

Amino Acids↗
PubMed1988

Lung antibacterial defense mechanisms in infant and adult rats: implications for the pathogenesis of group B streptococcal infections in the neonatal lung.

We investigated factors that may contribute to lung infections in infants by studying the intrapulmonary responses to aerosols of three different types of organisms--group B streptococcus with and without type-specific capsule, Pseudomonas aeruginosa, and Staphylococcus aureus--in infant (12-h-old or 24-36-h-old) and adult (150 g, 6-w-old) rats. After aerosol exposure, the lung clearance rate of each organism varied inversely with the age of the animals, and the magnitude of the clearance defect was related more strongly to animal age than to the bacterial species. Fewer alveolar macrophages from infant animals phagocytosed each type of organism in vivo, and the rate of neutrophil accumulation in the lungs of infant animals was delayed. The neonatal lung functioned effectively, however, as an antibacterial barrier, as newborn animals survived an aerosolized inoculum that exceeded the LD50 by the subcutaneous route.

Aerosols↗
PubMed1988

Pulmonary responses to bronchoconstrictor agonists in the mouse.

Mice have been used in studies of the immunology or pathology of several different disorders affecting the lung. However, the value of the mouse for the analysis of pulmonary pathophysiology has been limited by the lack of methods for measuring lung function in the living animal. We report here the first method for measuring pulmonary conductance (GL) and compliance (Cdyn) in tracheostomized mechanically ventilated mice. We used this method to characterize the mouse's pulmonary responses to several putative bronchoconstrictor agonists. GL and Cdyn were decreased by intravenous infusions of methacholine, norepinephrine, or serotonin. Reproducible responses were not detected after infusions of histamine, prostaglandins D2 or F2 alpha, leukotrienes C4 or D4, substance P, or platelet-activating factor. The pattern of airway responsiveness to these agonists in the mouse is similar to that reported for the rat; in contrast to the rat, the mouse has many well-characterized strains or mutants with deficiencies of immunologic or inflammatory cells or mediators. As a result, this model offers unique advantages for identifying the roles of individual inflammatory cell types or mediators in pulmonary processes, including pulmonary anaphylaxis.

Animals↗
PubMed1988

The lung at high altitude: bronchoalveolar lavage in acute mountain sickness and pulmonary edema.

High-altitude pulmonary edema (HAPE), a severe form of altitude illness that can occur in young healthy individuals, is a noncardiogenic form of edema that is associated with high concentrations of proteins and cells in bronchoalveolar lavage (BAL) fluid (Schoene et al., J. Am. Med. Assoc. 256: 63-69, 1986). We hypothesized that acute mountain sickness (AMS) in which gas exchange is impaired to a milder degree is a precursor to HAPE. We therefore performed BAL with 0.89% NaCl by fiberoptic bronchoscopy in eight subjects at 4,400 m (barometric pressure = 440 Torr) on Mt. McKinley to evaluate the cellular and biochemical responses of the lung at high altitude. The subjects included one healthy control (arterial O2 saturation = 83%), three climbers with HAPE (mean arterial O2 saturation = 55.0 +/- 5.0%), and four with AMS (arterial O2 saturation = 70.0 +/- 2.4%). Cell counts and differentials were done immediately on the BAL fluid, and the remainder was frozen for protein and biochemical analysis to be performed later. The results of this and of the earlier study mentioned above showed that the total leukocyte count (X10(5)/ml) in BAL fluid was 3.5 +/- 2.0 for HAPE, 0.9 +/- 4.0 for AMS, and 0.7 +/- 0.6 for controls, with predominantly alveolar macrophages in HAPE. The total protein concentration (mg/dl) was 616.0 +/- 3.3 for HAPE, 10.4 +/- 8.3 for AMS, and 12.0 +/- 3.4 for controls, with both large- (immunoglobulin M) and small- (albumin) molecular-weight proteins present in HAPE.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
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 association between low birth weight and caffeine consumption during pregnancy.

In a prospective study of 3,891 antenatal patients at Yale-New Haven Hospital between 1980 and 1982, 76.7% consumed caffeine from coffee, tea, colas, and drugs. A dose response of caffeine intake to increased risk for delivering low birth weight (less than 2,500 g) singleton newborns was observed. This relation was observed in deliveries after 36 weeks gestational age. When comparison was made with women who had no caffeine exposure, the relative risks of low birth weight after adjustment for confounding factors were 1.4 (95% confidence interval (CI) 0.7-3.0) for 1-150 mg of caffeine daily; 2.3 (95% CI 1.1-5.2) for 151-300 mg; and 4.6 (95% CI 2.0-10.5) for over 300 mg. Decreases in mean birth weight were 6, 31, and 105 g, respectively. Gestational age did not appear to be related to caffeine consumption in the crude or adjusted analysis. Maternal caffeine intake seems to exert an effect on birth weight through growth retardation in term newborns.

Adult↗
PubMed1987

Lung endothelial and epithelial permeability after platelet-activating factor.

We investigated whether platelet-activating factor (PAF) increased epithelial or endothelial permeability in isolated-perfused rabbit lungs. PAF was either injected into the pulmonary artery or instilled into the airway of lungs perfused with Tyrode's solution containing 1% bovine serum albumin. The effect of adding neutrophils or platelets to the perfusate was also tested. Perfusion was maintained 20-40 min after adding PAF and then a fluid filtration coefficient (Kf) was determined to assess vascular permeability. At the end of each experiment, one lung was lavaged, and the lavagate protein concentration (BALP) was determined. Wet weight-to-dry weight ratios (W/D) were determined on the other lung. PAF added to the vascular space increased peak pulmonary arterial pressure (Ppa) from 13.5 +/- 3.1 (mean +/- SE) to 24.2 +/- 3.3 cmH2O (P less than 0.05). The effect was amplified by platelets [Ppa to 70.8 +/- 8.0 cmH2O (P less than 0.05)] but not by neutrophils [Ppa to 22.0 +/- 1.4 cmH2O (P less than 0.05)]. Minimal changes in Ppa were observed after instilling PAF into the airway. The Kf, W/D, and BALP of untreated lungs were not increased by injecting PAF into the vasculature or into the air space. The effect of PAF on Kf, W/D, and BALP was unaltered by adding platelets or neutrophils to the perfusate. PAF increases intravascular pressure (at a constant rate of perfusion) but does not increase epithelial or endothelial permeability in isolated-perfused rabbit lungs.

Animals↗
PubMed1987

Airway size is related to sex but not lung size in normal adults.

Within individuals, lung size as assessed by total lung capacity (TLC) or vital capacity (VC) appears to be unrelated to airway size as assessed physiologically by maximum expiratory flows (MEF). Green et al. (J. Appl. Physiol. 37: 67-74, 1974) coined the term dysanapsis (unequal growth) to express this apparent interindividual discrepancy between parenchymal and airway size. We have reexamined this discrepancy using both physiological and anatomic indexes of airway size. Airway area by acoustic reflectance (AAAR), peak expiratory flow rates (PEFR), MEF, and lung volumes were measured in 26 male and 28 female healthy nonsmoking adults. The effect of sex on these indexes of large airway size was significant when assessed in a subset of males and females whose TLC's were matched (5.0-6.5 liters). Within this subset, male AAAR was 2.79 +/- 0.45 cm2, whereas female AAAR was 1.99 +/- 0.67 cm2 (P less than 0.01). Male's PEFR and MEF after 25% of VC had been expired (MEF25) were 23% greater than those of females within this subset (P less than 0.05). For the entire group of subjects, once these sex-related differences had been accounted for, AAAR was not significantly related to TLC, whereas PEFR and MEF25 remained at best weakly related to TLC. We conclude that tracheal areas in males are significantly larger than those of females even after controlling for TLC and that after controlling for sex-related differences, tracheal size in adults is unrelated to lung size across a broad range of lung sizes.

Adult↗
PubMed1987

Procoagulant activity in bronchoalveolar lavage in the adult respiratory distress syndrome. Contribution of tissue factor associated with factor VII.

Alveolar fibrin deposition commonly occurs in the lungs of patients with the adult respiratory distress syndrome (ARDS). Bronchoalveolar lavage (BAL) from patients with ARDS, control patients with interstitial lung disease (ILD), congestive heart failure, or exposure to hyperoxia, and normal healthy subjects was studied to determine whether local alterations in procoagulant activity favor alveolar fibrin deposition in the lungs in ARDS. Procoagulant activity capable of shortening the recalcification time of plasma deficient in either factor VII or factor VIII was observed in unconcentrated BAL of all patients, but was significantly greater in BAL from patients with ARDS when compared with that of control subjects (p less than 0.001). Unconcentrated BAL from patients with ARDS shortened the recalcification time of plasma deficient in factor X, but no functional thrombin was detectable. BAL procoagulant from patients with ARDS was inhibited by concanavalin A, an inhibitor of tissue factor. The hydrolysis of purified human factor X by BAL from the ARDS and other patient groups was determined by measuring the amidolytic activity of generated factor Xa on its N-benzoyl-L-isoleucyl-L-glutamyl-glycyl-L-arginine-p-nitroanilide substrate. The procoagulant activity of BAL was associated with the development of amidolytic activity, indicating activation of factor X. BAL from patients with ARDS contained more factor X activating activity than did BAL from control groups (p less than 0.001). This activity was calcium dependent and was maximal at 1 mM ionized calcium. The BAL factor X activating activity was most active at neutral pH and was sedimented by ultracentrifugation at 100,000 x g.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Relative contribution of leukotriene B4 to the neutrophil chemotactic activity produced by the resident human alveolar macrophage.

Human alveolar macrophages release chemotactic activity for neutrophils, providing a role for alveolar macrophages in regulating inflammation in the lung. As alveolar macrophages produce large amounts of leukotriene B4 (LTB4), a chemotactically active lipoxygenase product of arachidonic acid, we investigated the contribution of LTB4 to the total neutrophil chemotactic activity produced by these cells. Normal human alveolar macrophages were recovered by bronchoalveolar lavage from healthy volunteers and incubated either with the calcium ionophore A23187 for 1 h, or with opsonized zymosan particles or latex beads for 3 h. Nordihydroguaretic acid (NDGA), a relatively specific lipoxygenase inhibitor, blocked the release of neutrophil chemotactic activity after all three stimuli in a dose-dependent manner. This correlated with blockade of LTB4 production as measured by high performance liquid chromatography using freshly isolated alveolar macrophages, as well as blockade of [3H]LTB4 production by macrophages prelabeled with [3H]arachidonate. Molecular sieve chromatography using Sephadex G-50 confirmed that essentially all of the chemotactic activity in the stimulated macrophage supernatants co-eluted with authentic [3H]LTB4, and that NDGA completely blocked the chemotactic activity in the eluting fractions. Readdition of authentic LTB4 (1 X 10(-7) M) to the NDGA-blocked macrophage supernatants restored the chemotactic activity in the supernatants. The macrophage supernatants did not contain platelet-activating factor-like activity, as measured by the stimulation of [3H]serotonin release from rabbit platelets, and by high performance liquid chromatography. NDGA did not change the protein-secretion profiles of fresh alveolar macrophages, or of macrophages prelabeled with [35S]methionine. The complement (C) components C5adesarg were not detected in any of the supernatants by radioimmunoassay. Concentration of the supernatants by positive pressure filtration (5,000-D membrane) did not augment chemotactic activity in the stimulated supernatants or uncover chemotactic activity in the NDGA-blocked supernatants. As with the 3-h studies, when alveolar macrophages were incubated overnight with opsonized zymosan, all of the increase in chemotactic activity could also be blocked by NDGA. These data indicate that LTB4 is the predominant neutrophil chemotactic factor secreted by the normal resident human alveolar macrophage in response to two major types of stimuli, calcium fluxes across the cell membrane and the phagocytosis of opsonized particulates.

Calcimycin↗