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Biomedical subjects

Keith C Meyer

Publications and source records attributed to Keith C Meyer.

13 recordsLinked to original sources
PubMed2005

Aging.

Respiratory tract infections are a leading cause of morbidity and mortality in the elderly. Many factors, such as malnutrition and the presence of structural lung disease, increase the risk of respiratory infection in older individuals. Aging is also accompanied by a gradual decline in many aspects of immune function, and waning immunity is thought to be an important risk factor for pneumonia in the elderly. Although a generalized decline in both the cell-mediated and humoral aspects of acquired immunity have been described in otherwise normal elderly populations, relatively little is known about the effect of age on compartmentalized pulmonary immune surveillance and immune responses to a challenge with a respiratory pathogen. Changes in immune cell profiles and acellular components of bronchoalveolar secretions have been detected by bronchoalveolar lavage, but the impact of these changes on host defense against respiratory infections is unknown. An improved understanding of the age-associated changes in pulmonary host defense mechanisms and how these might be manipulated to reduce the susceptibility of the elderly to respiratory tract infections may reduce the possibility of severe debilitation and death and the considerable health care burden posed by the increased incidence of pneumonia in this at-risk population.

Age Factors↗
PubMed2004

Quantitative and qualitative analysis of rhinovirus infection in bronchial tissues.

Although rhinovirus (RV) infections can cause asthma exacerbations and alter lower airway inflammation and physiology, it is unclear how important bronchial infection is to these processes. To study the kinetics, location, and frequency of RV appearance in lower airway tissues during an acute infection, immunohistochemistry and quantitative polymerase chain reaction analysis were used to analyze the presence of virus in cells from nasal lavage, sputum, bronchoalveolar lavage, bronchial brushings, and biopsy specimens from 19 subjects with an experimental RV serotype 16 (RV16) cold. RV was detected by polymerase chain reaction analysis on cells from nasal lavage and induced sputum samples from all subjects after RV16 inoculation, as well as in 5 of 19 bronchoalveolar lavage cell samples and in 5 of 18 bronchial biopsy specimens taken 4 days after virus inoculation. Immunohistochemistry detected RV16 in 39 and 36% of all biopsy and brushing samples taken 4 and 15 days, respectively, after inoculation. Infected cells were primarily distributed in discrete patches on the epithelium. These results confirm that infection of lower airway tissues is a frequent finding during a cold and further demonstrate a patchy distribution of infected cells, a pattern similar to that reported in upper airway tissues.

Adult↗
PubMed2004

Role of sensory input from the lungs in control of muscle sympathetic nerve activity during and after apnea in humans.

We reasoned that, if the lung inflation reflex contributes importantly to apnea-induced sympathetic activation, such activation would be attenuated in bilateral lung transplant recipients (LTX). We measured muscle sympathetic nerve activity (MSNA; intraneural electrodes), heart rate, mean arterial pressure, tidal volume, end-tidal Pco(2), and arterial oxygen saturation in seven LTX and seven healthy control subjects (Con) before, during, and after 20-s end-expiratory breath holds. Our evidence for denervation in LTX was 1) greatly attenuated respiratory sinus arrhythmia and 2) absence of cough reflex below the level of the carina. During apnea, the temporal pattern and the peak increase in MSNA were virtually identical in LTX and Con (347 +/- 99 and 359 +/- 46% of baseline, respectively; P > 0.05). In contrast, the amount of MSNA present in the first 5 s after resumption of breathing was greater in LTX vs. Con (101 +/- 4 vs. 38 +/- 7% of baseline, respectively; P < 0.05). There were no between-group differences in apnea-induced hypoxemia or hypercapnia, hemodynamic, or ventilatory responses. Thus cessation of the rhythmic sympathoinhibitory feedback that normally accompanies eupneic breathing does not contribute importantly to sympathetic excitation during apnea. In contrast, vagal afferent input elicited by hyperventilation-induced lung stretch plays an important role in the profound, rapid sympathetic inhibition that occurs after resumption of breathing after apnea.

Adult↗
PubMed2004

Lung infections and aging.

Respiratory tract infections are the leading cause of death due to infectious disease in the elderly. Many factors, especially waning immune responses and the onset of age-associated organ dysfunction, likely account for an increase in susceptibility to respiratory tract infection in the elderly, and morbidity and mortality rates are substantially greater for the elderly when outcomes are compared to that of younger individuals. The presence of underlying disease states such as chronic obstructive pulmonary disease (COPD) or other organ system disease further increases the likelihood of developing severe pneumonia in the elderly population, and the frail elderly, particularly when institutionalized in chronic care facilities, are at high risk for developing severe and recurrent pneumonia. This article will discuss various factors associated with advanced age that predispose the elderly to respiratory infections and summarize current approaches to treatment and prevention.

Aging↗
PubMed2004

The role of bronchoalveolar lavage in interstitial lung disease.

Considerable progress has been made in understanding the similarities and differences among the forms of the interstitial lung diseases (ILDs), particularly the forms of idiopathic interstitial pneumonia, now recognized as distinct clinicopathologic entities. Lung parenchymal evaluation by high-resolution CT scanning of the chest may provide images that are virtually diagnostic of certain forms of ILD, but other testing, including bronchoalveolar lavage (BAL) and lung biopsy, may be required for accurate diagnosis. The differential diagnosis of these disorders rests on the clinician's interpretation of the clinical presentation and physical examination findings, pulmonary function testing, radiographic imaging, and, if required, sampling of lung tissue. This discussion examines the usefulness of BAL in the diagnosis of specific forms of ILD.

Biopsy↗
PubMed2004

Drug treatment of pneumococcal pneumonia in the elderly.

Streptococcus pneumoniae has been recognised as a major cause of pneumonia since the time of Sir William Osler. Drug-resistant S. pneumoniae (DRSP), which have gradually become resistant to penicillins as well as more recently developed macrolides and fluoroquinolones, have emerged as a consequence of indiscriminate use of antibacterials coupled with the ability of the pneumococcus to adapt to a changing antibacterial milieu. Pneumococci use cell wall choline components to bind platelet-activating factor receptors, colonise mucosal surfaces and evade innate immune defenses. Numerous virulence factors that include hyaluronidase, neuraminidase, iron-binding proteins, pneumolysin and autolysin then facilitate cytolysis of host cells and allow tissue invasion and bloodstream dissemination. Changes in pneumococcal cell wall penicillin-binding proteins account for resistance to penicillins, mutations in the ermB gene cause high-level macrolide resistance and mutations in topoisomerase IV genes coupled with GyrA gene mutations alter DNA gyrase and lead to high-level fluoroquinolone resistance. Risk factors for lower respiratory tract infections in the elderly include age-associated changes in oral clearance, mucociliary clearance and immune function. Other risks for developing pneumonia include poor nutrition, hypoalbuminaemia, bedridden status, aspiration, recent viral infection, the presence of chronic organ dysfunction syndromes including parenchymal lung disease and recent antibacterial therapy. Although the incidence of infections caused by DRSP is rising, the effect of an increase in the prevalence of resistant pneumococci on mortality is not clear. When respiratory infections occur, rapid diagnosis and prompt, empirical administration of appropriate antibacterial therapy that ensures adequate coverage of DRSP is likely to increase the probability of a successful outcome when treating community-acquired pneumonia in elderly patients, particularly those with multiple risk factors for DRSP. A chest x-ray is recommended for all patients, but other testing such as obtaining a sputum Gram's smear is not necessary and should not prolong the time gap between clinical suspicion of pneumonia and antibacterial administration. The selection of antibacterials should be based upon local resistance patterns of suspected organisms and the bactericidal efficacy of the chosen drugs. If time-dependent agents are chosen and DRSP are possible pathogens, dosing should keep drug concentrations above the minimal inhibitory concentration that is effective for DRSP. Treatment guidelines and recent studies suggest that combination therapy with a beta-lactam and macrolide may be associated with a better outcome in hospitalised patients, and overuse of fluoroquinolones as a single agent may promote quinolone resistance. The ketolides represent a new class of macrolide-like antibacterials that are highly effective in vitro against macrolide- and azalide-resistant pneumococci. Pneumococcal vaccination with the currently available polysaccharide vaccine is thought to confer some preventive benefit (preventing invasive pneumococcal disease), but more effective vaccines, such as nonconjugate protein vaccines, need to be developed that provide broad protection against pneumococcal infection.

Aged↗
PubMed2003

Pre-transplant mechanical ventilation and outcome in patients with cystic fibrosis.

Mechanical ventilation for ventilatory failure has been considered a relative contraindication to subsequent lung transplantation. The purpose of this study was to test the hypothesis that patients with cystic fibrosis (CF) who are intubated and mechanically ventilated before transplantation have poorer post-transplant outcomes than do patients who are not ventilated. We compared the outcomes of 8 patients with CF who underwent mechanical ventilation for 62 +/-20 days (range, 3-153 days) before bilateral lung transplantation with outcomes of 24 patients with CF who did not undergo pre-transplant mechanical ventilation. Although time to extubation after transplantation was prolonged significantly (11 vs 4 days) for the pre-transplant ventilated group, days to hospital discharge, forced expiratory volume in 1 second (percent predicted) at 1 year after transplantation, and post-transplant survival as determined using the Kaplan-Meier method did not differ statistically between the 2 groups. Patients with CF who undergo pre-transplant endotracheal intubation and mechanical ventilation for respiratory failure have outcomes that do not differ significantly from those of patients with CF who do not require invasive ventilatory support before bilateral lung transplantation.

Adult↗
PubMed2003

Aspergillus infection in lung transplant recipients with cystic fibrosis: risk factors and outcomes comparison to other types of transplant recipients.

STUDY OBJECTIVES: To characterize Aspergillus infections in lung transplant recipients with cystic fibrosis (CF). DESIGN: A retrospective analysis of 32 consecutive lung transplant recipients with CF who underwent bilateral lung transplant at the University of Wisconsin from 1994 to 2000 to determine the incidence, risk factors, and consequences of Aspergillus infection. The findings were compared to 101 non-CF recipients of lung transplants (93) and heart-lung transplants (8) for other transplant indications. SETTING: A university hospital. PATIENTS OR PARTICIPANTS: Lung transplant recipients with CF or other indications for transplantation. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Seventeen of 32 CF recipients (53%) had Aspergillus fumigatus isolated from their respiratory secretions prior to undergoing transplantation. Ten of these 17 (59%) recipients had A fumigatus persistently found in their respiratory secretions posttransplant vs 6 of 15 CF patients (40%) who had not been colonized pretransplant and 28 of 101 of the non-CF recipients (28%). Four of the preoperatively colonized CF recipients developed tracheobronchial aspergillosis (TBA) just distal to the bronchial anastomoses, and one recipient had dehiscence of the involved anastomosis. None of the CF recipients developed disseminated aspergillosis or pneumonia. Prophylactic antifungal therapy did not prevent TBA, and IV amphotericin B therapy was required to clear the infection in all four patients, with endobronchial debridement of necrotic tissue required in two of them. In contrast, 10 of the non-CF (10%) recipients developed Aspergillus infections posttransplant (TBA, 4 recipients; pneumonitis, 6 recipients), and only 3 patients had successful treatment and long-term survival (TBA, 2 patients; pneumonia, 1 patient). Donor lung ischemia time, cytomegalovirus infection or pneumonia, or pretransplant mechanical ventilation did not increase the risk of developing TBA in CF recipients. CONCLUSIONS: The risk of TBA for patients receiving lung transplants for CF warrants early surveillance bronchoscopy to detect TBA, particularly in recipients with pretransplant colonization.

Adult↗
PubMed2002

Inflammation and surfactant.

An intact and well-functioning pulmonary surfactant system is critical for normal respiration and protection from lung infection. Surfactant is comprised of phospholipids that reduce surface tension and greatly reduce the work of breathing. The other major component consists of surfactant-associated proteins, which optimise the biophysical function of phospholipids and/or play an important role in host defence by acting as collectins. Alteration of surfactant composition and function occurs with various inflammatory disorders that affect the airways or the lung parenchyma including asthma, infant respiratory distress syndrome/bronchopulmonary dysplasia, cystic fibrosis, acute respiratory distress syndrome and interstitial lung disease. Although surfactant replacement therapy is indicated for infant respiratory distress syndrome, there is no well-proven role for exogenous surfactant in the treatment of inflammatory lung disorders at the present time.

Age Factors↗
PubMed2002

Role of lung inflammatory mediators as a cause of exercise-induced arterial hypoxemia in young athletes.

We examined whether lung inflammatory mediators are increased during exercise and whether pharmacological blockade can prevent exercise-induced arterial hypoxemia (EIAH) in young athletes. Seventeen healthy athletes (9 men, 8 women; age 23 +/- 3 yr) with varying degrees of EIAH completed maximal incremental treadmill exercise tests after administration of fexofenadine, zileuton, and nedocromil sodium or placebo in a randomized double-blind crossover study. Lung function, arterial blood gases, and inflammatory metabolites in plasma, urine, and induced sputum were assessed. Drug administration did not improve EIAH or gas exchange during exercise. At maximal exercise, oxygen saturation fell to 91.4 +/- 2.6% (drug trial) and 91.9 +/- 2.1% (placebo trial) and alveolar-arterial oxygen difference widened to 28.1 +/- 6.3 Torr (drug trial) and 29.3 +/- 5.7 Torr (placebo trial). Oxygen consumption, ventilation, and other exercise variables were similarly unaffected by drug treatment. Although plasma histamine increased with exercise, values did not differ between trials, and urinary leukotriene E(4) and 11beta-prostaglandin F(2alpha) levels were unchanged after exercise. Postexercise sputum revealed no significant changes in markers of inflammation. These results demonstrate that EIAH in young athletes is not attenuated with acute administration of drugs targeting histamine and bioactive lipids. We conclude that airway inflammation is of insufficient magnitude to cause impairments in gas exchange and does not appear to be linked to EIAH in healthy young athletes.

Adult↗
PubMed2002

Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients.

Current theories of CF pathogenesis predict different predisposing "local environmental" conditions and sites of bacterial infection within CF airways. Here we show that, in CF patients with established lung disease, Pseudomonas aeruginosa was located within hypoxic mucopurulent masses in airway lumens. In vitro studies revealed that CF-specific increases in epithelial O(2) consumption, linked to increased airway surface liquid (ASL) volume absorption and mucus stasis, generated steep hypoxic gradients within thickened mucus on CF epithelial surfaces prior to infection. Motile P. aeruginosa deposited on CF airway surfaces penetrated into hypoxic mucus zones and responded to this environment with increased alginate production. With P. aeruginosa growth in oxygen restricted environments, local hypoxia was exacerbated and frank anaerobiosis, as detected in vivo, resulted. These studies indicate that novel therapies for CF include removal of hypoxic mucus plaques and antibiotics effective against P. aeruginosa adapted to anaerobic environments.

Adult↗