Papers by Philip Bromberg
Therapeutic Advances in Respiratory Disease, 2009
Objective: Intrapleural fibrinolytic enzymes have been used for over 60 years in the treatment of... more Objective: Intrapleural fibrinolytic enzymes have been used for over 60 years in the treatment of complicated pleural effusions to lyse loculations and promote resolution. Despite this extensive history of use, however, little is known about complications that may arise with the use of this therapy. Here we discuss a patient with chronic renal failure on hemodialysis who developed an intrapleural hemorrhage after the administration of intrapleural tPA to treat a complicated parapneumonic effusion. A review of the literature examines the efficacy and safety of this therapy, focusing on bleeding complications. Specific attention is paid to patients who have underlying coagulopathies or who are receiving anticoagulation. Data sources: A review of the literature, as indexed in PubMed, was undertaken using the following search terms in combination: tPA, pleural effusion, complications of thrombolytics, and intrapleural hemorrhage. The search was inclusive of patients under the age of 18, but was limited by English language and human subjects. Study selection/data extraction: All relevant articles identified during the search were reviewed. Those studies that reported on bleeding complications, or lack thereof, were included in this review. Limitations of each article are noted in the text. Conclusions: Multiple studies, including a 2000 ACP consensus statement and a 2008 Cochrane review, indicate the need for further investigations to evaluate the safety and efficacy of intrapleural thrombolytics for the treatment of complicated pleural effusions and empyemas. Limited studies specifically address bleeding complications, especially in subpopulations of patients receiving concurrent anticoagulant therapy.
Chemical research in toxicology, Jan 25, 2015
Oxidative stress is a commonly cited mechanism of toxicity of environmental agents. Ubiquitous en... more Oxidative stress is a commonly cited mechanism of toxicity of environmental agents. Ubiquitous environmental electrophiles such as the diesel exhaust component 1,2-naphthoquinone (1,2-NQ) induce oxidative stress by redox cycling, which generates hydrogen peroxide (H2O2). Cysteinyl thiolate residues on regulatory proteins are subjected to oxidative modification by H2O2 in physiological contexts, and are also toxicological targets of oxidant stress induced by environmental contaminants. We investigated whether exposure to environmentally relevant concentrations of 1,2-NQ can induce H2O2-dependent oxidation of cysteinyl thiols in regulatory proteins as a readout of oxidant stress in human airway epithelial cells. BEAS-2B cells were exposed to 0-1000 µM 1,2-NQ for 0-30 min and levels of H2O2 were measured by ratiometric spectrofluorometry of HyPer. H2O2-dependent protein sulfenylation was measured using immunohistochemistry, immunoblotting and isotopic mass spectrometry. Catalase overex...
Journal of applied physiology (Bethesda, Md. : 1985), 1994
Fifteen men were exposed to 6,683 ppm C18O for 3.09-6.65 min. Arterial and antecubital vein blood... more Fifteen men were exposed to 6,683 ppm C18O for 3.09-6.65 min. Arterial and antecubital vein blood samples were drawn at 1-min intervals beginning at the start of C18O inhalation and ending 10 min later. Simultaneously, alveolar ventilation was calculated from the measured values of minute ventilation and dead space. All other parameters of the Coburn-Forster-Kane equation (CFKE), except the Haldane affinity ratio, were measured separately in each subject. Means of CFKE predictions of increases in venous HbCO (delta HbCO) in samples collected approximately 2 min after cessation of exposure were accurate, but the range in errors of prediction for individual subjects was +/- 3.8% HbCO, depending on the time after exposure cessation. Increases in venous and arterial HbCO were inaccurately predicted during and immediately after HbCO formation, however. Venous blood was overestimated during CO uptake because of a delayed appearance of HbCO. Individual subjects differed markedly in the deg...
Studies in Environmental Science, 1989
Journal of Bronchology, 1998
ABSTRACT
Southern Medical Journal, 1987
Plasma cell granulomas of the lung are usually benign tumors found incidentally on chest x-ray fi... more Plasma cell granulomas of the lung are usually benign tumors found incidentally on chest x-ray film, though some have been found to be locally invasive. Our report of a plasma cell granuloma recurring 11 years after the initial resection emphasizes that complete surgical resection should be done whenever possible.
Respiration, 1981
Forced oscillatory resistance (RFO) and compliance (CFO) were measured in 3 groups of adult beagl... more Forced oscillatory resistance (RFO) and compliance (CFO) were measured in 3 groups of adult beagle dogs. Group I (n = 12) had undergone a left pneumonectomy at 6-10 weeks of age; group II (n = 11) underwent a similar procedure at 1 year of age; and group III (n = 8) served as unoperated controls. The mean value of RFO for group II was significantly higher than corresponding values for groups I and III. Similarly, the mean value of CFO was significantly lower for group II. Mean values for RFO and CFO between groups I and III were not statistically different. When RFO and CFO were normalized by functional residual capacity, mean values for all three groups were similar. However, when RFO and CFO were normalized by body weight, mean values for groups I and II were significantly different from those of group III. These findings cannot be explained directly by postoperative hyperinflation of the remaining lung. They suggest that there is an adaptive change in the mechanical characteristics of the remaining lung following pneumonectomy and that the degree of adaptation varies with the age of the animal undergoing resection.
Journal of the American College of Cardiology, 1988
Acute exposure to carbon monoxide has the potential to impair exercise capacity in patients with ... more Acute exposure to carbon monoxide has the potential to impair exercise capacity in patients with isdlemic heart disease. The effect of sufficient inhalation of this compound to gradually produce a level of 6% carboxyhemoglobin was studied in 30 nonsmoking patients with obstructive coronary artery disease and evidence of exerelsednduced iseb . ends . After an initial training session, subjects were exposed to air or carbon monoxide on successive days in a randomized double-blind crossover fashion . Cardiac function and exercise capacity were assessed during symptomlimited supine radionuclide ventrknlography . On the earbon monoxide day, mean postexposure carboxyhemoglobin was 5 .9 ± 0.1% compared with 1 .6 ± 0.1% (p < 0.01) after air exposure.
Journal of Allergy and Clinical Immunology, 2005
We have been studying the innate immune response of airways cells of healthy human volunteers to ... more We have been studying the innate immune response of airways cells of healthy human volunteers to inhaled LPS, a Toll-like receptor 4 (TLR4) ligand, and have shown that macrophage phagocytic capacity is blunted. Because a primary feature of dendritic cell (DC) maturation is a loss of phagocytic capacity, we sought to determine whether acute LPS inhalation in healthy volunteers promotes DC maturation in vivo. Phagocytosis (IgG-opsonized zymosan particles) and cell-surface phenotypes were analyzed by flow cytometry of induced sputum cells obtained before and 6 hours after Clinical Center Reference Endotoxin (CCRE; 20,000 EU) inhalation in 9 healthy volunteers. Neutrophils were elevated in the airways after CCRE inhalation (67% +/- 6% vs 37% +/- 6%; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05). Phagocytosis (monocytes, macrophages) was blunted (73%, 46%; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05) and negatively correlated with PMN influx ( R = -0.73; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05) after CCRE inhalation. GM-CSF and IL-1beta, potent DC maturation agents, were elevated after versus before CCRE inhalation (217 pg/mL +/- 103 pg/mL vs 722 pg/mL +/- 202 pg/mL; 83 pg/mL +/- 24 pg/mL vs 148 pg/mL +/- 37 pg/mL, respectively; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05). Markers of DC maturation (CD80, CD86, HLA-DR) were upregulated on monocytes and macrophages ( P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05), and discrete populations of mature DC were observed ( P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05) after CCRE inhalation. Inhaled LPS, directly through TLR4 stimulation of immature DC and/or indirectly through stimulation of GM-CSF and IL-1beta, induces pulmonary DC maturation in vivo . Inhaled LPS may enhance allergic airways responses to air pollution through its ability to induce DC maturation.
Journal of Allergy and Clinical Immunology, 1999
Recent observations show that atopic asthmatic subjects have increased sensitivity to respirable ... more Recent observations show that atopic asthmatic subjects have increased sensitivity to respirable endotoxin (or LPS) compared with normal persons. In vitro studies demonstrate that LPS enhances eosinophil survival. These observations suggest that the effects of inhaled LPS in asthmatic subjects may include increases in the number of airway eosinophils. We sought to determine whether low-level nasal LPS challenge causes an increase in eosinophil numbers in the nasal airways of atopic or normal subjects. Sixteen volunteers (10 atopic asthmatic subjects and 6 normal subjects) underwent 2 nasal challenge sessions. In one session, one nostril was challenged with saline and the other with 0. 1 microg of LPS. During the second session, 0.3 microg and 1.0 microg of LPS was delivered to each nostril, respectively. Nasal lavage fluid was obtained from each nostril before challenge, as well as 4 and 24 hours after challenge, and examined for the percent of total cells that were eosinophils and neutrophils, as well as cytokine levels. LPS (1.0 microg) increased the percent of eosinophils in nasal lavage fluid 4 hours after challenge in atopic subjects only. There was also a correlation between constitutive nasal GM-CSF and eosinophil response to LPS in atopic subjects. LPS challenge increases eosinophils in the airways of atopic subjects.
Journal of Allergy and Clinical Immunology, 2003
Letters to the editor FIG 1. Effect of endotoxin on PC 20 FEV 1 to D Farinae allergen after 4-hou... more Letters to the editor FIG 1. Effect of endotoxin on PC 20 FEV 1 to D Farinae allergen after 4-hour exposure to 500 ng/m 3 of endotoxin and clean air.
Inhalation Toxicology, 2010
The effects of low-level ozone exposure (0.08 ppm) on pulmonary function in healthy young adults ... more The effects of low-level ozone exposure (0.08 ppm) on pulmonary function in healthy young adults are well known; however, much less is known about the inflammatory and immunomodulatory effects of low-level ozone in the airways. Techniques such as induced sputum and flow cytometry make it possible to examine airways inflammatory responses and changes in immune cell surface phenotypes following low-level ozone exposure. The purpose of this study was to determine if exposure to 0.08 parts per million ozone for 6.6 h induces inflammation and modifies immune cell surface phenotypes in the airways of healthy adult subjects. Fifteen normal volunteers underwent an established 0.08 part per million ozone exposure protocol to characterize the effect of ozone on airways inflammation and immune cell surface phenotypes. Induced sputum and flow cytometry were used to assess these endpoints 24 h before and 18 h after exposure. The results showed that exposure to 0.08 ppm ozone for 6.6 h induced increased airway neutrophils, monocytes, and dendritic cells and modified the expression of CD14, HLA-DR, CD80, and CD86 on monocytes 18 h following exposure. Exposure to 0.08 parts per million ozone is associated with increased airways inflammation and promotion of antigen-presenting cell phenotypes 18 hours following exposure. These findings need to be replicated in a similar experiment that includes a control air exposure.
Archives of Environmental Health: An International Journal, 1987
We studied 30 patients 38-75 yr of age who had ischemic heart disease to assess the effect of acu... more We studied 30 patients 38-75 yr of age who had ischemic heart disease to assess the effect of acute elevation of carboxyhemoglobin (COHb) concentration. Patients were nonsmokers with ischemia defined by exercise-induced ST depression (ST decreases)--25/30, angina--23/30, or abnormal ejection fraction (EF) response--18/30. After an initial familiarization and exercise session patients were exposed to air (carboxyhemoglobin [COHb] = 1.5 +/- 0.05%) and to carbon monoxide (CO) (100 ppm-COHb-average = 3.8 +/- 0.1%) on successive days in a double blind, randomized fashion. There was no significant difference in time to onset of angina (air = 312 sec, CO = 306 sec), maximal exercise time (air = 711 sec, CO = 702 sec), maximal ST decreases (1.5 mm for both), or time to significant ST decreases (air = 474 sec, CO = 475 sec). Double product at ST decreases and maximal double products were similar for both conditions. Resting ejection fraction was slightly but nonsignificantly higher after CO exposure (air = 53.9%, CO = 55.2%). Maximal ejection fraction was similar for both conditions (air = 57.4%, CO = 57.1%). Change in ejection fraction was slightly lower for CO exposure (air = 3.5%, CO = 2%), p = .049. In conclusion, there is no clinically significant effect of 3.8% COHb (representing a 2.2% increase from resting values) on the cardiovascular system in this study.
American Journal of Medical Genetics, 1999
Primary ciliary dyskinesia (PCD) is a genetic disease characterized by abnormal ciliary structure... more Primary ciliary dyskinesia (PCD) is a genetic disease characterized by abnormal ciliary structure and function, impaired mucociliary clearance, and chronic middle ear, sinus, and lung disease. PCD is associated with situs inversus in approximately 50% of the patients. One proposed explanation for this relationship is that normal ciliary function plays a role in normal organ orientation, whereas organ orientation in PCD is a random event because of dysfunctional cilia in early embryonic development. Another hypothesis for the association between PCD and situs inversus is that mutated genes in PCD not only cause defective cilia, but are also linked to the control of organ laterality, such that abnormalities in this molecular pathway result in random left-right asymmetry. We report on a set of monozygotic twin women with PCD. In both patients, deficiency of the inner dynein arms was noted on ciliary ultrastructural analysis, associated with a clinical syndrome of bronchiectasis, chronic sinusitis, and middle ear disease. One of the twins has situs solitus, the other has situs inversus totalis. DNA analysis confirmed that the twins are monozygotic. This is consistent with the hypothesis that situs inversus occurring in patients with primary ciliary dyskinesia is a random but &amp;amp;quot;complete&amp;amp;quot; event in the fetal development of patients with PCD.
Cyclooxygenase 2 (COX-2) expression is induced by physiological and inflammatory stimuli. Regulat... more Cyclooxygenase 2 (COX-2) expression is induced by physiological and inflammatory stimuli. Regulation of COX-2 expression is stimulus and cell type specific. Exposure to Zn2+ has been associated with activation of multiple intracellular signaling pathways as well as the induction of COX-2 expression. This study aims to elucidate the role of intracellular signaling pathways in Zn2+-induced COX-2 expression in human bronchial epithelial cells. Inhibitors of the phosphatidylinositol 3-kinase (PI3K) potently block Zn2+-induced COX-2 mRNA and protein expression. Overexpression of adenoviral constructs encoding dominant-negative Akt kinase downstream of PI3K or wild-type phosphatase and tensin homolog deleted on chromosome 10, an important PI3K phosphatase, suppresses COX-2 mRNA expression induced by Zn2+. Zn2+ exposure induces phosphorylation of the tyrosine kinases, including Src and EGF receptor (EGFR), and the p38 mitogen-activated protein kinase. Blockage of these kinases results in inhibition of Zn2+-induced Akt phosphorylation as well as COX-2 protein expression. Overexpression of dominant negative p38 constructs suppresses Zn2+-induced increase in COX-2 promoter activity. In contrast, the c-Jun NH2-terminal kinase and the extracellular signal-regulated kinases have minimal effect on Akt phosphorylation and COX-2 expression. Inhibition of p38, Src, and EGFR kinases with pharmacological inhibitors markedly reduces Akt phosphorylation induced by Zn2+. However, the PI3K inhibitors do not show inhibitory effects on p38, Src, and EGFR. These data suggest that p38 and EGFR kinase-mediated Akt activation is required for Zn2+-induced COX-2 expression and that the PI3K/Akt signaling pathway plays a central role in this event.
Wehave,previously shown,that exposure to zinc ions can activate EGF receptor (EGFR) signaling in ... more Wehave,previously shown,that exposure to zinc ions can activate EGF receptor (EGFR) signaling in murine,fibroblasts and A431 cells through a mechanism involving Src kinase. While studying the effects of zinc ions in normal human bronchial epithelial cell, we uncovered,evidence ,for an additional ,mechanism ,of Zn,-induced EGFR activation.
Particle and fibre toxicology, Jan 9, 2004
BACKGROUND: Exposure to fine particulate matter air pollutants (PM2.5) affects heart rate variabi... more BACKGROUND: Exposure to fine particulate matter air pollutants (PM2.5) affects heart rate variability parameters, and levels of serum proteins associated with inflammation, hemostasis and thrombosis. This study investigated sources potentially responsible for cardiovascular and hematological effects in highway patrol troopers. RESULTS: Nine healthy young non-smoking male troopers working from 3 PM to midnight were studied on four consecutive days during their shift and the following night. Sources of in-vehicle PM2.5 were identified with variance-maximizing rotational principal factor analysis of PM2.5-components and associated pollutants. Two source models were calculated. Sources of in-vehicle PM2.5 identified were 1) crustal material, 2) wear of steel automotive components, 3) gasoline combustion, 4) speed-changing traffic with engine emissions and brake wear. In one model, sources 1 and 2 collapsed to a single source. Source factors scores were compared to cardiac and blood para...
Particle and fibre toxicology, 2011
Concerns over the health effects of nanomaterials in the environment have created a need for micr... more Concerns over the health effects of nanomaterials in the environment have created a need for microscopy methods capable of examining the biological interactions of nanoparticles (NP). Unfortunately, NP are beyond the diffraction limit of resolution for conventional light microscopy (~200 nm). Fluorescence and electron microscopy techniques commonly used to examine NP interactions with biological substrates have drawbacks that limit their usefulness in toxicological investigation of NP. EM is labor intensive and slow, while fluorescence carries the risk of photobleaching the sample and has size resolution limits. In addition, many relevant particles lack intrinsic fluorescence and therefore can not be detected in this manner. To surmount these limitations, we evaluated the potential of a novel combination of darkfield and confocal laser scanning microscopy (DF-CLSM) for the efficient 3D detection of NP in human lung cells. The DF-CLSM approach utilizes the contrast enhancements of da...
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Papers by Philip Bromberg