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Biomedical subjects

G W Waterer

Publications and source records attributed to G W Waterer.

At least 19 recordsLinked to original sources
PubMed2005

Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well functioning elderly subjects.

BACKGROUND: Inflammatory markers are increased in chronic obstructive pulmonary disease (COPD) and are hypothesised to play an important part in muscle dysfunction and exercise intolerance. METHODS: The Health Aging and Body Composition (Health ABC) study is a prospective observational cohort of well functioning individuals aged 70-79 years. A cross sectional analysis of the baseline data was conducted to examine the association between inflammatory markers and ventilatory limitation, muscle strength, and exercise capacity. These associations were compared in participants with and without obstructive lung disease (OLD). RESULTS: Of the 3075 participants enrolled in the Health ABC cohort, OLD was identified by spirometric testing in 268 participants and 2005 participants had normal spirometric results. Of the participants with OLD, 35%, 38%, and 27% participants had mild, moderate, and severe OLD, respectively. Participants with OLD had lower quadriceps strength (102.5 Nm v 108.9 Nm, p = 0.02), lower maximum inspiratory pressure (64.7 cm H(2)O v 74.2 cm H(2)O, p<0.0001), higher systemic interleukin (IL)-6 levels (2.6 pg/ml v 2.2 pg/ml, p<0.0001), and higher C-reactive protein (CRP) levels (3.5 mg/l v 2.5 mg/l, p<0.0001) than those with normal spirometry. In participants with OLD and those with normal spirometry, forced expiratory volume in 1 second (FEV(1)) was associated with IL-6 (adjusted regression coefficients (beta) = -5.3 (95% CI -9.1 to-1.5) and -3.1 (95% CI -4.3 to -1.9), respectively). IL-6 and TNF were also associated with quadriceps strength among participants with OLD and those with normal spirometry (beta = -6.4 (95% CI -12.8 to -0.03) and -3.4 (95% CI -5.4 to -1.3), respectively, for IL-6 and beta = -10.1 (95% CI -18.7 to -1.5) and -3.8 (95% CI -7 to -0.6), respectively, for TNF). IL-6, quadriceps strength, and maximum inspiratory pressures were independent predictors of reduced exercise capacity in both groups. CONCLUSIONS: In well functioning elderly subjects with or without OLD, IL-6 is associated with reduced FEV(1), quadriceps strength, and exercise capacity.

Aged↗
PubMed2005

Significance of positive Stenotrophomonas maltophilia culture in acute respiratory tract infection.

Stenotrophomonas maltophilia is a common coloniser of the respiratory tract of patients with chronic lung disease, and, in the absence of pneumonia or bacteraemia, is often ignored by physicians at the Royal Perth Hospital (Perth, Australia). Experience at the Royal Perth Hospital was reviewed to determine whether ignoring S. maltophilia in this setting has any apparent effect on clinical outcome. All patients who presented with an acute respiratory illness and yielded a positive culture for S. maltophilia between 1995 and 2002 were retrospectively reviewed. All subjects had to yield a positive respiratory isolate of S. maltophilia and undergo chest radiography within 24 h of the isolate being obtained. Ninety-two episodes were identified in 89 individuals; 64 showed no evidence of consolidation. Of the study group, 51 (80.0%) received no anti-S. maltophilia antibiotic therapy and 21 (32.8%) had a nosocomially acquired isolate. The overall mortality rate was 20.3%. There was no impact of anti-S. maltophilia therapy on outcome. The only independent predictor of mortality was serum albumin level. As there was no measurable impact of antibiotic therapy, in the absence of consolidation, a positive respiratory tract isolate of Stenotrophomonas maltophilia probably represents colonisation of a severely impaired host rather than invasive disease.

Acute Disease↗
PubMed2003

Polymorphisms in lymphotoxin alpha and CD14 genes influence TNFalpha production induced by Gram-positive and Gram-negative bacteria.

Improved understanding of how host genetic variation affects resistance to microbial pathogens could lead to better treatment and/or prevention of infectious diseases. The lymphotoxin alpha (LTA)+250 and CD14-159 polymorphisms are associated with differences in susceptibility or outcome to several infections. We stimulated peripheral blood mononuclear cells (PBMC) from 22 healthy individuals with purified lipopolysaccharide (LPS), heat-killed Escherichia coli or Streptococcus pneumoniae. TNF alpha intracellular protein levels were measured by flow cytometry and mRNA was quantitated by RT-PCR. TNF alpha mRNA levels were higher in LTA+250GG subjects after 4 h incubation with LPS compared with LTA+250AA (T test, P=0.001). In contrast, after 8 h incubation with S. pneumoniae, there was slightly more TNF alpha mRNA in cells from LTA+250AA subjects. After 4 h incubation with LPS or E. coli, CD14-159TT subjects had higher TNF alpha mRNA levels than CD14-159CC (P=0.05, 0.033, respectively). Neither polymorphism affected the proportion of cells expressing intracellular TNF alpha protein. This suggests that the polymorphisms affected transcription and that other regulatory mechanisms affect production of TNF alpha protein. The effect of these two polymorphisms on TNF alpha mRNA production is stimulus dependent, with opposite effects observed for Gram-positive and Gram-negative stimuli.

Genetic Predisposition to Disease↗
PubMed2001

Legionella and community-acquired pneumonia: a review of current diagnostic tests from a clinician's viewpoint.

Many physicians are unaware of the limitations of the available tests for diagnosing infections with Legionella organisms. Geographic differences in the importance of nonpneumophila Legionella species as pathogens are underrecognized, in part because available diagnostic tests are biased toward the detection of pneumophila serogroup 1. Routine laboratory practices reduce the likelihood of culturing Legionella species from clinical isolates. Failure of seroconversion is common, particularly with nonpneumophila species; even when seroconversion occurs, it may take much longer than 4 weeks. Urinary antigen testing has insufficient sensitivity to affect clinical management in most regions of the United States, as it can reliably detect only L. pneumophila serogroup 1 infections. Polymerase chain reaction-based techniques offer hope of providing highly sensitive, rapid diagnostic tests for all Legionella species, but limitations in the current tests will make validating them difficult.

Antigens, Bacterial↗
PubMed2001

Controversies in the diagnosis of ventilator-acquired pneumonia.

The appropriate investigation of patients with suspected VAP is controversial. Because it is unlikely that any new diagnostic technique will become available in the near future with better performance characteristics than those currently available, physicians need to tailor their diagnostic approach depending on individual patients and clinical scenarios. The most crucial factor in deciding which diagnostic approach to take is the influence that any test result would have on management. If preliminary screening tests, including Gram stain, are used to determine whether to start antibiotic therapy, invasive diagnostic techniques have an advantage over ETA. Quantitative cultures of respiratory specimens have a higher specificity than qualitative cultures and should be used if there is any possibility that a negative culture result would result in the discontinuation of antibiotic therapy. Physicians are caught between the need to treat VAP promptly with appropriate antibiotics and the undeniable problems of multidrug-resistant bacteria and their association with inappropriate antibiotic use. When clinically possible, a diagnostic strategy should be chosen that maximizes the possibility of limiting broad-spectrum antibiotic use. To give physicians greater comfort in the ability to withhold or discontinue antibiotics safely, further research is needed into the appropriate diagnostic strategies in different clinical settings that make this possible. The studies by Fagon et al and Singh et al are important steps in this direction.

Algorithms↗
PubMed2001

Airflow limitation is underrecognized in well-functioning older people.

OBJECTIVES: Dyspnea is a common symptom in older people. A reduced forced expiratory volume in 1 second (FEV1) is associated with a higher mortality rate from cardiovascular and respiratory disease, and increased admissions to hospitals. Underrecognized or undertreated airflow limitation may exacerbate the problem. The purpose of this study was to assess the prevalence and treatment of airflow limitation in a cohort of well-functioning older people. DESIGN: Cross-sectional study. SETTING: Baseline of a clinical-epidemiological study of incident functional limitation. PARTICIPANTS: Participants attended the baseline examination of the Health, Aging, and Body Composition study, a prospective cohort study of 3,075 well-functioning subjects age 70 to 79. MEASUREMENTS: Demographic and clinical data were collected by interview. Spirometry was performed unless contraindicated and repeated until three acceptable sets of flow-volume loops were obtained. Patients on bronchodilator medications had spirometry performed posttherapy. Blinded readers assessed the flow-volume loops, and inadequate tests were omitted from analysis. Airflow limitation was defined as a reduced forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) as determined by age-, sex-, and race-normalized values. Severity of airflow limitation was defined by American Thoracic Society criteria. RESULTS: Two thousand four hundred eighty-five subjects (80.8%) had assessable spirometry and data on treatment and diagnosis (1,265 men, 1,220 women). The mean age was 73.6 years. Two hundred sixty-two subjects (10.5%) had airflow limitation; 43 (16.4%) of these never smoked. Only 37.4% of participants with airflow limitation and 55.6% of participants with severe airflow limitation reported a diagnosis of lung disease. Only 20.5% of subjects with at least moderate airflow limitation had used a bronchodilator in the previous 2 weeks. CONCLUSION: Despite their good functional status, airflow limitation was present, and underrecognized, in a considerable proportion of our older population. The low bronchodilator use suggests a significant reservoir of untreated disease. Physicians caring for older people need to be more vigilant for both the presence, and the need for treatment, of airflow limitation.

Aged↗
PubMed2001

The influence of the severity of community-acquired pneumonia on the usefulness of blood cultures.

The value of blood cultures in community-acquired pneumonia (CAP) has been questioned. At issue is the potential for blood cultures to change management. We prospectively studied the yield and impact of blood cultures in patients admitted with CAP. Two hundred and nine subjects had at least two blood cultures prior to receiving antibiotics. The severity of CAP was graded using the Pneumonia Severity Index (PSI). Twenty-nine patients (13.9%) had a pathogen identified by blood culture. The yield of blood cultures increased with PSI grade (I--5.3%, II--10.2%, III--10.3%, IV--16.1%, V--26.7%), as did the likelihood of blood cultures changing antibiotic therapy (I to III--0%, IV--9.7%, V--20.0%). One hundred and seventy-nine (85.6%) patients received a quinolone, limiting the impact of pathogens resistant to beta-lactams. Four of 16 patients (25.0%) with a culture (blood or sputum)-guided change in antibiotic therapy died, compared to five of 31 patients (16.1%) who had an empiric change. Blood cultures are of minimal value in mild to moderate CAP, and should be limited to patients with PSI grade IV or V CAP unless a specific risk factor for pathogens resistant to the empiric therapy is present.

Adolescent↗
PubMed2001

Increasing threat of Gram-negative bacteria.

The widespread use of broad-spectrum antibiotics has led to emergence of antibiotic-resistant strains of many Gram-negative organisms. This problem is particularly serious in critically ill patients, especially those with ventilator-associated pneumonia. Extensive antibiotic resistance has developed in Gram-negative bacteria, due both to innate resistance in some species and the fact that they are highly adept at acquiring antibiotic-resistant determinants from each other. Antibiotic resistance develops through the following three basic mechanisms: alteration of the drug target, prevention of drug access to the target (including actively removing the drug from the bacteria), and drug inactivation. Certain Gram-negative microorganisms are particular problems in the intensive care unit, including Pseudomonas aeruginosa, Acinetobacter spp., Stenotrophomonas maltophilia, and the Enterobacteriaceae. The combination of an increasing population at risk, and the natural virulence and adaptability of Gram-negative bacteria guarantees that critical care physicians will face a persistent and increasing challenge from these pathogens.

Cross Infection↗
PubMed2001

Septic shock and respiratory failure in community-acquired pneumonia have different TNF polymorphism associations.

Genetic factors are likely to contribute to the variable presentation of community-acquired pneumonia (CAP). The purpose of this prospective cohort study was to determine whether the LTalpha+250 (TNFbeta+250) and TNFalpha-308 gene polymorphisms are associated with different presentations of CAP. Septic shock (SS) was defined using American College of Chest Physicians/Society of Critical Care Medicine (ACCP-SCCM) criteria. Type I respiratory failure (T1RF) was defined as an O(2) saturation on room air of < 90% with a normal PCO(2). A total of 280 patients were genotyped; 31 had SS, 80 had T1RF. Genotype proportions are given in the order of AA/GA/ GG. The proportion of patients in each genotype developing SS was as follows: LTalpha+250 0.19/0.07/0.09 (p = 0.01 AA versus non-AA); TNFalpha-308 0.16/0.06/0.12 (p = NS). Carrying at least one AA (tumor necrosis factor [TNF] high secretor) genotype had an 18.0% risk of SS versus 6.8% (p = 0.006). GG homozygotes (TNF low secretors) at both loci had only a 2.9% risk of SS. Septic shock was associated with the LTalpha+250:TNFalpha-308 A:G haplotype but not the A:A haplotype, suggesting that LTalpha+250 is a marker, rather than a causative polymorphism. Carriage of the G:G haplotype had a significant protective effect against the development of septic shock (p = 0.011). T1RF was not associated with LTalpha+250 AA genotype. In the absence of septic shock, there was a significant trend to greater T1RF in patients with LTalpha+250 GG (TNFalpha hyposecretor) genotype (p = 0.03). Our finding of different genotype associations for SS and T1RF has important implications for immunotherapy in both CAP and sepsis, as well as for the definition of the systemic inflammatory response syndrome (SIRS).

Adolescent↗
PubMed2000

Reducing electrostatic charge on spacer devices and bronchodilator response.

AIMS: Plastic spacers are widely used with pressurized metered dose inhalers (pMDI). Reducing electrostatic charge by washing spacers with detergent has been shown to greatly improve in vitro and in vivo drug delivery. We assessed whether this finding is associated with an improved bronchodilator response in adult asthmatics. METHODS: Twenty subjects (age 18-65 years) with a known bronchodilator response inhaled in random order salbutamol from a pMDI (Ventolin) through an untreated new spacer (Volumatic) and through a detergent washed spacer. Patients received the following doses of salbutamol via pMDI at 20 min intervals: 100 microg, 100 microg, 200 microg, 400 microg, 800 microg. Spirometry, heart rate and blood pressure were checked prior to each dose and 20 min after the last dose. RESULTS: There were no differences between baseline forced expiratory volume in 1 s (FEV1) using either spacer (2.61+/-0.56 and 2.52+/-0.45 l, untreated and treated with detergent, respectively; mean +/- s.d.). The provocation dose required to cause a clinically significant improvement of 10% in FEV1 (PD10) was significantly lower when the detergent treated spacer was used (1505 +/-1335 and 430+/-732 microg, untreated and treated, respectively, P<0.002). CONCLUSIONS: We have demonstrated an improvement in bronchodilator response, in adult asthmatics, after reducing the electrostatic charge in a spacer device by washing it with ordinary household detergent. This finding stresses the importance of an optimal choice of delivery device for asthma medication.

Adolescent↗
PubMed1999

Pulmonary capillaritis associated with the antiphospholipid antibody syndrome and rapid response to plasmapheresis.

OBJECTIVE: Pulmonary capillaritis is an uncommon complication of antiphospholipid antibody syndrome but has important therapeutic implications. CASE REPORT: A patient with antiphospholipid antibody syndrome presented with haemoptysis and respiratory failure. Investigation including open lung biopsy, demonstrated vasculitis as the underlying pathology, rather than thrombosis. The patient responded promptly to methylprednisolone, cyclophosphamide and plasmapheresis. CONCLUSION: Plasmapheresis has not previously been described in this setting and the rapid response suggests that it should be considered in severe disease.

Antiphospholipid Syndrome↗
PubMed1999

The impact of blood cultures on antibiotic therapy in pneumococcal pneumonia.

INTRODUCTION: The cost-effectiveness of blood cultures in community-acquired pneumonia (CAP) has been questioned. Although penicillin-resistant Streptococcus pneumoniae is an increasing problem, penicillin therapy, where appropriate, reduces cost and may reduce antibiotic resistance. Blood cultures, however, can only reduce cost if physicians are prepared to alter therapy based on the results. We reviewed our experience to determine how often physicians changed management based on blood culture results positive for S pneumoniae. METHODS: Retrospective chart review was performed of all CAP admissions between January 1996 and December 1998 with blood culture results positive for S pneumoniae. RESULTS: Seventy-four patients out of 1,805 patients admitted with CAP during this period had pneumococcemia. Penicillin resistance was identified in 15 cases (20.3%; high grade in 4 cases) with cephalosporin resistance in 4 of these cases (1 high grade). Fifty-one patients had initial empiric therapy with a third-generation cephalosporin, and 58 patients had empiric coverage of atypical organisms; no patient received empiric penicillin therapy. Blood culture results altered management in 31 patients (41.9%), but in only 2 cases was this due to antibiotic resistance. Fifty-one patients without penicillin allergy grew penicillin-sensitive pneumococci; only 11 patients (21.6%) were changed to penicillin therapy. Thirteen of 35 patients (37.1%) who were given an additional antibiotic for atypical coverage had this antibiotic ceased. CONCLUSION: Despite evidence of penicillin-sensitive pneumococcal CAP, physicians were reluctant to narrow antibiotic therapy, potentially adding to treatment cost and reducing the impact of blood culture results on management. The impact of penicillin resistance was reduced by the usual empiric choice of a third-generation cephalosporin. While positive blood culture results can clearly be useful in the management of patients with CAP, their cost-effectiveness needs to be assessed in prospective clinical trials.

Blood↗