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Biomedical subjects

C D Beaty

Publications and source records attributed to C D Beaty.

7 recordsLinked to original sources

The utility of a single sputum specimen in the diagnosis of tuberculosis. Comparison between HIV-infected and non-HIV-infected patients.

STUDY OBJECTIVES: (1) To assess the utility of a single sputum specimen in the evaluation of HIV-infected patients who are suspected of having tuberculosis (TB). (2) To identify radiographic findings that discriminate between HIV-infected patients with TB and those with pneumonia of other causes. DESIGN: Retrospective cohort analysis. PATIENTS: All patients evaluated at Harborview Medical Center, Seattle, between January 1986 and July 1994 in whom culture of respiratory secretions grew Mycobacterium tuberculosis or Mycobacterium avium-complex. Patients who were coinfected with HIV formed the primary study group. Their chest radiographs were then compared with those of a matched group of patients with pneumonia of other causes. MEASUREMENTS AND RESULTS: We identified 164 patients with TB, 20 of whom were HIV infected. The initial sputum specimen grew M tuberculosis in all HIV-infected patients and 99% of non-HIV-infected patients. Seventy percent of HIV-infected and 71% of non-HIV-infected patients had at least one positive smear. Most of these patients tested positive on their initial smear, and no significant difference was found between HIV-positive and HIV-negative patients (79% and 90%, respectively [p = 0.34]). The addition of a second sputum smear identified all HIV-infected patients and all but one in non-HIV-infected patients who were ultimately determined to be smear positive. A total of 27 HIV-infected patients had a positive acid-fast bacilli sputum smear during the study period, 14 of which were attributable to TB (specificity = 52%). The only radiographic findings that discriminated between HIV-infected patients with TB and those with pneumonia of other causes were the presence of cavitation or a miliary pattern (p = 0.014). CONCLUSIONS: A single sputum specimen was sufficient to establish the diagnosis in all HIV-infected patients with pulmonary TB. A single negative sputum smear made the diagnosis of TB significantly less likely. However, a minimum of two smears were necessary to achieve an acceptable early diagnostic yield. The presenting chest radiograph failed to discriminate between HIV-infected patients with TB and pneumonia of other causes in most cases.

AIDS-Related Opportunistic Infections↗

Lipopolysaccharide-induced cytokine production in human monocytes: role of tyrosine phosphorylation in transmembrane signal transduction.

The signal transduction events that follow the binding of lipopolysaccharide (LPS) to the macrophage cell surface are not well defined. In the current studies LPS was found to induce alterations in phosphorylation of monocyte proteins on tyrosine. Herbimycin A and genistein, inhibitors of tyrosine kinases, markedly attenuated LPS-induced tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) protein and mRNA production. Reciprocally, the tyrosine phosphatase inhibitor sodium orthovanadate enhanced LPS-induced production of TNF-alpha. LPS induced a concentration-dependent increase in tyrosine phosphorylation of several proteins, which paralleled and preceded the onset of LPS-induced TNF-alpha production. LPS stimulation had different but reproducible effects on three members of the src family of tyrosine kinases. Both Hck and Lyn kinase activity increased before the onset of TNF-alpha production, consistent with their participation in the observed LPS-induced tyrosine phosphoprotein accumulation. In contrast, Yes kinase activity was not affected. These observations were made at concentrations of LPS that required serum rich in LPS-binding protein and the monocyte surface antigen CD14 for TNF-alpha production. These data indicate that tyrosine kinases and phosphatases are involved in the signal transduction cascade by which LPS induces production of TNF-alpha and IL-6 by human monocytes, and suggest that Lyn and Hck are candidate participants in this process.

Acute-Phase Proteins↗

Chlamydia pneumoniae, strain TWAR, infection in patients with chronic obstructive pulmonary disease.

TWAR, the only known serovar of Chlamydia pneumoniae, is a newly described bacterium that has been identified as a cause of both epidemics and endemic cases of pneumonia. The role of TWAR infection in patients with chronic obstructive pulmonary disease (COPD) is not known. We conducted a prospective study to establish whether TWAR infection is a common cause of acute exacerbations of COPD. We studied two groups of patients: 44 patients admitted to the hospital with acute exacerbations of COPD, and 65 stable clinic patients with COPD. We found that evidence of acute TWAR infection was infrequent in patients with exacerbations (5%). In contrast, the majority of patients from both groups had serologic evidence of previous TWAR infection (77%). This was not significantly greater than the prevalence found in a small group of patients of similar age and sex without lung disease from the same institution (73%). TWAR was not isolated from the oropharyngeal specimens obtained from 97 subjects, suggesting that it does not colonize the respiratory tract of patients with COPD. This study shows that at the time of low incidence in the community, acute TWAR infection is uncommon in patients with acute exacerbations of COPD. The majority of patients with COPD have, however, been infected with TWAR in the past. The clinical manifestations of these infections are not known and should be the focus of further studies.

Aged↗

Signal transduction in human alveolar macrophages: diminished chemotactic response to FMLP correlates with a diminished density of Gi proteins and FMLP receptors.

Alveolar macrophages (AM) migrate less well in response to chemotactic ligands than do monocytes and neutrophils. The response of monocytes and neutrophils to chemotactic ligands is mediated at least in part by pertussis toxin-sensitive guanine nucleotide binding proteins (Gi proteins). Whether this is also true in AM is uncertain. We hypothesized that decreased chemotaxis by AM was due in part to diminished Gi protein and/or chemotactic receptor density in AM. G proteins are heterotrimers made up of alpha, beta, and gamma subunits; the predominant pertussis toxin-sensitive Gi proteins are those containing alpha i2 or alpha i3 subunits. Pertussis toxin pretreatment (0.5 microgram/ml) significantly reduced AM, monocyte, and neutrophil chemotaxis to N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) and human zymosan-activated serum (P less than 0.05). However, as previously noted, AM chemotaxis was much less than that observed in monocytes and neutrophils. Immunoblots using antibodies that are specific for alpha i2 and alpha i3 showed that AM contained approximately 3-fold less alpha i2 and approximately 10-fold less alpha i3 per microgram of plasma membrane protein than did monocytes or neutrophils. Similar results were obtained in immunoblots made using antibodies to common alpha subunit determinants and to the beta 36 subunit. A comparable approximately 4-fold reduction in density of receptors for [3H]FMLP was found in AM compared to neutrophils. The diminished density of Gi proteins and FMLP receptors was not due to a generally decreased density of plasma membrane proteins in AM, since the density of the membrane-associated tyrosine kinase hck was similar in AM, monocytes, and neutrophils.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Continuous in-line nebulizers complicate pressure support ventilation.

Patients ventilated in the pressure support mode must generate a negative airway pressure before the ventilator will deliver a breath. Inserting a continuous-flow nebulizer between the patient and the sensor in the ventilator makes it more difficult for the patient to generate this negative pressure. We observed two mechanically ventilated patients who were unable to initiate ventilator breaths in the pressure support mode while bronchodilators were being administered through a continuous-flow nebulizer. In neither case did ventilator alarms sound. Using a lung model, we found that when the nebulizer flow rate exceeded the mean inspiratory flow rate of the test lung, the negative pressure necessary to trigger the pressure support ventilator could not be generated. Critical care providers need to be aware of this potential complication, since it may lead to serious underventilation of their patients.

Administration, Inhalation↗