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Biomedical subjects

A K Pierce

Publications and source records attributed to A K Pierce.

At least 19 recordsLinked to original sources
PubMed1990

Fibronectin is not detectable on the intact buccal epithelial surface of normal rats or humans.

Fibronectin (FN) has been postulated to prevent gram-negative bacillary (GNB) colonization of the oropharynx by covering epithelial cell GNB receptors. We investigated the distribution of FN along the luminal surface of oropharyngeal epithelium in animals and humans. Examination of buccal epithelial biopsies obtained from normal rats revealed no luminal surface FN by either immunofluorescent or immunoperoxidase staining. Extraction of epithelial surface proteins and quantitation of FN by rocket immunoelectrophoresis and electrophoretic transfer to nitrocellulose followed by immunologic detection also detected no FN from normal animals' oropharyngeal biopsies. Buccal epithelial biopsies from three normal humans were examined for FN using electrophoretic transfer to nitrocellulose followed by immunologic detection, and no FN was demonstrable. Our results suggest that FN is not present on the oral epithelial surface of healthy rodents or humans, and that FN may not be involved in the pathogenesis of bacillary colonization.

Animals↗
PubMed1988

Treatment of pneumonia in patients at risk of infection with gram-negative bacilli.

Patients with a history of chronic debilitating disease due to a variety of causes are known to be at risk for infection with coliform gram-negative bacilli when they present with community-acquired pneumonia. Empiric treatment with broad-spectrum parenteral antibiotics is often begun in such patients pending the result of blood and other cultures. The optimal duration of broad-spectrum empiric therapy in such patients when cultures fail to reveal a specific pathogen is unknown. Review was made of the charts of 131 patients with community-acquired pneumonia admitted to the hospital and treated with broad-spectrum parenteral antibiotics in whom a specific pathogen was never isolated. Overall, 89 percent of these patients were cured without complication or relapse. Patients receiving broad-spectrum therapy for four days or less due to rapid clinical improvement had a successful outcome in 95 percent of cases. It is concluded that broad-spectrum parenteral antibiotic therapy can safely be abbreviated provided response to therapy is prompt.

Aminoglycosides↗
PubMed1987

Increased salivary elastase precedes gram-negative bacillary colonization in postoperative patients.

The upper airway epithelium is coated with fibronectin, a glycoprotein that covers receptor sites for gram-negative bacteria and prevents them from colonizing the oropharynx. We investigated the identity of salivary proteolytic enzymes capable of degrading fibronectin in a group of 16 patients who had elective cardiac surgery. Six patients became colonized with gram-negative bacteria (Group C) and 10 did not (Group NC). Salivary elastase activity was low in both groups preoperatively. Twenty-four hours after surgery, salivary elastase activity increased in Group C, and it remained elevated at 48 and at 72 h. Fibronectin digestive activity of the saliva of patients in Group C was also increased within 24 h of surgery, and salivary elastase and fibronectin digestive activity were highly correlated (r = 0.86, p less than 0.001). Enzyme inhibition experiments showed that most of the fibronectin digestive activity was due to elastase from polymorphonuclear cells (PMN), and the molecular weight of the salivary enzyme digesting fibronectin was 30,000 daltons (similar to the molecular weight of elastase). Levels of antileukoprotease, the major elastase inhibitor in saliva, were normal in patients with increased elastase activity. We conclude that salivary elastase is of PMN origin, increases prior to gram-negative bacillary colonization of the pharynx, and is responsible for most of the fibronectin digestive activity of the saliva.

Cardiac Surgical Procedures↗
PubMed1985

The effects of systemic immunization of pulmonary clearance of Pseudomonas aeruginosa.

Systemic immunization with gram-negative organisms enhances the subsequent pulmonary clearance of these organisms. We studied the early time course of this phenomenon and related it to the time of appearance of polymorphonuclear leukocytes (PMN) and anti-Pseudomonas antibody in bronchoalveolar lavage (BAL). Mice were immunized intraperitoneally twice, separated by 1 wk, with 10(8) formalin-treated Pseudomonas aeruginosa. Two weeks later, they received an intrabronchial inoculum of 2.9 X 10(6) or 4.6 X 10(7) Pseudomonas organisms. Two, 4, and 6 h later, clearance and total PMN and anti-Pseudomonas antibody in the BAL were assessed. Clearance was enhanced in immunized mice at the lower inoculum. At the higher inoculum, bacteria were growing in lungs of both groups, although they were inhibited in immunized mice. Total PMN in the BAL increased progressively in both groups of mice, but net recruitment was diminished with the high inoculum. There were significant differences in the PMN in the BAL between control and immunized mice with high inoculum. Anti-Pseudomonas IgG first appeared in the BAL at 2 h, anti-Pseudomonas IgM at 6 h. These data suggest that anti-Pseudomonas IgG is an effective early pulmonary opsonin. Further, with high inoculums, immunization may aid pulmonary defenses by diminishing the magnitude of the decrement of PMN in the lung.

Animals↗
PubMed1985

Pulmonary elastase activity in response to Streptococcus pneumoniae and Pseudomonas aeruginosa.

Elastase activity generated during lung defense against aerobic bacteria was studied in an animal model. Bronchoalveolar lavage (BAL) fluid from hamsters inoculated with bacteria was assayed for elastase activity at 0, 2, 4, 6, and 8 h after inoculation using a synthetic substrate of elastase, succinyl-trialanine-nitroanilide (SLAPN). Streptococcus pneumoniae type 25 inoculation led to a peak elastase activity of 0.72 +/- 0.27 X 10(-3) units, not significantly different from baseline (0.41 +/- 0.08 X 10(-3) units) or saline control (0.33 +/- 0.18 X 10(-3) units). In contrast, inoculation with Pseudomonas aeruginosa strain PAO-1 (a species known to produce elastase as well as other virulence factors) produced peak elastase activity of 3.0 +/- 1.2 X 10(-3) units in BAL fluid, significantly higher than either pneumococcus type 25 or saline control (p less than 0.025). Inoculation with Pseudomonas aeruginosa strain E-64, an isogenic mutant of PAO-1 that produces a nonfunctional elastase, led to peak levels similar to the PAO-1 strain, suggesting that the presence of bacterial elastase was not the primary factor in BAL fluid elastase activity. Total numbers of granulocytes in BAL fluid from pneumococcus-inoculated animals (144 +/- 31 X 10(6] was significantly higher (p less than 0.05) than from either the PAO-1 (74 +/- 31 X 10(6] or E-64 (99 +/- 27 X 10(6] strains of Pseudomonas, Use of selective enzyme inhibitors of elastase, diisopropyl fluorophosphate and disodium ethylenediaminetetraacetate, implied that the majority of elastase activity in BAL fluid was due to a serine protease, of which granulocyte elastase is the primary source.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Nosocomial pneumonia in patients in intensive care units.

Nosocomial pneumonia is a major cause of mortality among patients in intensive care units, despite recent advances in antimicrobial therapy. Aerobic Gram-negative bacilli remain the pathogens responsible for most of these pneumonias. These organisms colonize the oropharynx of severely ill patients, and their subsequent aspiration results in lower respiratory tract infection. Recent investigation into the pathogenesis of oropharyngeal bacterial colonization has shown the central importance of bacterial adherence mechanisms.

Aminoglycosides↗
PubMed1984

Early pulmonary granulocyte recruitment in response to Streptococcus pneumoniae.

Although polymorphonuclear leukocytes (PMN) are a conspicuous histologic feature of clinical and experimental pneumococcal pneumonia, neither the mechanism nor the magnitude of recruitment of these cells to the lung following lesser pneumococcal challenge is known. We have, therefore, investigated the early process of recruitment of PMN to alveolar spaces after pulmonary inoculation of Streptococcus pneumoniae in doses less than those causing pneumonia. We injected Balb/c mice with water and varying inoculums of pneumococci via an endobronchial catheter. Bronchoalveolar lavage (BAL) was performed on the inoculated lung at 0, 2, or 4 h after injection. Cellular response was measured and chemotactic activity was assayed on BAL supernatants at each time interval using the migration of human PMN through 3-micron filters in modified Boyden chambers by the leading front techniques. The BAL of normal and control animals (inoculum of sterile water only used for the control animals) yielded 5.03 +/- 1.51 X 10(2) and 0.17 +/- 0.04 X 10(5) PMN, respectively. The PMN recruitment at 4 h as a function of pneumococcal inoculum was described by the following equation: log PMN = 0.751 log Pn + 1.119 (r2 = 0.82, p less than 0.001). The PMN were, therefore, recruited in a dose-dependent manner. That recruitment may be caused by chemotactic substance(s) was suggested by the significant correlation between the PMN response and the distance of in vitro migration: log PMN = 0.057 micron + 0.52 (r = 0.77, p less than 0.005). We have defined quantitatively the recruitment of PMN to the lung after pneumococcal challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

The fifth component of complement is not required for the clearance of Staphylococcus aureus.

Both resident alveolar macrophages and recruited polymorphonuclear leukocytes (PMN) are required for pulmonary clearance of large inoculums of Staphylococcus aureus. We have evaluated the role of the C5 molecule in the recruitment of PMN to the lung after challenges with S. aureus using congenic C5-sufficient B10.D2/nSn (C5+) and C5-deficient B10.D2/oSn (C5-) mice. The C5+ and C5- mice were injected with water and varying inoculums of staphylococci via an endobronchial catheter. Bronchoalveolar lavage (BAL) was performed on the inoculated lung at 0 and 4 h after inoculation. Cellular response was measured and chemotactic activity was assayed in BAL supernatants at each time interval using human PMN in modified Boyden chambers by the leading front technique. Clearance of bacteria was studied by quantitative lung culture. The C5+ and C5- mice recruited similar numbers of PMN after challenges with both 10(4), 10(8), and 10(7) organisms (p = NS). The C5+ and C5- mice also generated similar amounts of chemotactic activity in BAL (p = NS). Additionally, clearance of bacteria was not impaired in C5- mice when compared with that in C5+ mice (p = NS). Our results indicate that intraalveolar chemotaxins other than C5 are of primary importance in the early recruitment of PMN after staphylococcal challenge and demonstrate that the inflammatory response within the lung is mediated by differing pathways dependent on the initiating stimulus.

Animals↗
PubMed1983

Rapid diagnosis of community-acquired bacterial pneumonia.

Rapid identification of pathogens in patients with bacterial pneumonia is important for optimal antimicrobial therapy. Coagglutination was compared with counterimmunoelectrophoresis (CIE) for sensitivity and specificity in the detection of Streptococcus pneumoniae, Hemophilus influenzae, Klebsiella pneumoniae, and Pseudomonas aeruginosa antigens in sputum specimens of 101 patients with community-acquired pneumonia. Coagglutination detected the appropriate bacterial antigen in 16 of 17 (94%) definite etiology patients and CIE detected 11 (64%). In 17 probable etiology patients, bacterial antigens were detected by coagglutination in 15 (88%) and by CIE in 7 (41%). Only 1 pathogen was falsely identified in the 19 culture-negative control patients, indicating a high degree of specificity for both tests. Coagglutination was more sensitive than CIE (p less than 0.05) or sputum stained with Gram's stain (p less than 0.05) in correctly identifying the putative pathogen in sputum. Our results strongly suggest that coagglutination is a useful diagnostic technique for establishing a rapid etiologic diagnosis in community-acquired pneumonia.

Agglutination Tests↗
PubMed1983

A morphological study of the role of phagocytes in the clearance of Staphylococcus aureus from the lung.

A nonlethal dose of Staphylococcus aureus was inoculated into the mainstem bronchus of mice in order to study the influx of polymorphonuclear leukocytes (PMN). The goal was to determine the routes of entry of PMN into the lung following bacterial challenge, the relative importance of PMN as compared to alveolar macrophages (AM) in the uptake of S aureus, and the role of lymphatics in clearance of intact microorganisms. Resident AM took up S aureus within minutes of inoculation, but PMN were subsequently recruited to the lung and were the predominant cell containing S aureus by 4 hours following inoculation. PMN were recruited from arteries, capillaries, and venules. Emigration of PMN into alveolar spaces occurred between type I epithelial cells as well as between type I and type II epithelial cells. Lymphatics played only a minor role in the clearance of S aureus.

Animals↗
PubMed1982

Mechanisms of complement-mediated clearance of bacteria from the murine lung.

Complement factors enhance host defense against bacterial challenges by attracting phagocytic cells to the site of the inoculum and by opsonizing bacteria for phagocytic ingestion. The relative contribution of these 2 mechanisms to in vivo clearance of bacteria from the lung has not been described. Hypocomplementemic and normal animals were challenged with various bacteria. Clearance of bacteria was studied by quantitative lung culture. Phagocytic response was determined by bronchoalveolar lavage. Staphylococci were cleared by macrophages without regard to the complement status of the host. Hypocomplementemic animals cleared pneumococci less efficiently than did control animals. This defect correlated with decreased neutrophil recruitment. Pseudomonas was not cleared in hypocomplementemic animals, but there was no difference in the number or type of phagocytes. This implies that an opsonic rather thn a chemotactic defect was responsible. These data suggest that the mechanism of complement-mediated defense against bacterial challenge varies with the type of pathogen present.

Animals↗
PubMed1981

Pulmonary clearance and phagocytic cell response to normal pharyngeal flora.

Because human lungs are repetitively inoculated with the normal bacterial flora of the pharynx, we determined the pulmonary clearance of representative species after aerosol inoculation of a murine model, and characterized the phagocytic cell response by bronchoalveolar lavage. Viable bacteria remaining in the lungs at 1, 2, and 4 h were: Streptococcus sanguis, 24%, 8%, and 1%; Streptococcus salivarius, 49%, 24%, and 5%; Neisseria catarrhalis, 69%, 49%, and 22%. Clearance of Streptococcus sanguis was associated with a twofold increase in alveolar macrophages (p less than 0.05); Streptococcus salivarius evoked a doubling of alveolar macrophages and a 20-fold rise in granulocytes (p less than 0.05); the response to Neisseria catarrhalis was a 400-fold increase in granulocytes (p less than 0.05). Thus, normal pharyngeal organisms are cleared rapidly from the lung by a dual phagocytic cell system. It is speculated that bacteria-phagocyte interaction allows the possibility of lung injury from proteolytic enzymes released from either set of phagocytes.

Animals↗
PubMed1980

A new method of perineal reconstruction following vulvectomy.

We propose a method in which vulvar reconstruction could be accomplished at the time of vluvectomy. A full-thickness pedicle flap is rotated from the vaginal vault to the area of excision, providing excellent coverage without subsequent contracture, and obviating the need for clitorectomy. This technique may also aid in palliating the psychological trauma induced by genital disfigurement.

Adult↗
PubMed1980

Pulmonary function measurements in patients with thermal injury and smoke inhalation.

We performed serial pulmonary function measurements in 28 patients with thermal injury in order to investigate the pulmonary effects of smoke inhalation, small and large surface burns, and the combination of burn and inhalation. Patients were studied at postinjury time intervals of 9.0 +/- 0.6 (M +/- SEM), 22.0 +/- 1.6, 37.3 +/- 2.2, 58.4 +/- 2.5 hours; 11.5 +/- 0.6 days; 1.1 +/- 0.1 and 5.0 +/- 0.5 months. Spirometry was found to be as useful as more sophisticated measurements in the examination of both burn and smoke inhalation groups. Smoke inhalation caused severe airway obstruction 9 h after exposure. Patients with surface burn resuscitated with 4 ml of Ringer's lactate/per cent surface area burn/kilogram developed a significant restrictive defect over the first 58 h, despite normal pulmonary capillary wedge pressures. The restrictive defect in these patients correlated with the size of surface and chest burn, degree of fluid retention, and reduction in colloid osmotic pressure. Surface burn and smoke inhalation caused the greatest deterioration in pulmonary function. These defects gradually resolved during the period of observation.

Adult↗