Pneumocystis carinii pneumonia in patients with primary brain tumors.

All histologically documented episodes of Pneumocystis carinii pneumonia in adult patients with primary brain tumors treated at Memorial Sloan-Kettering Cancer Center, New York, NY, since 1981, were retrospectively reviewed. Pneumocystis carinii pneumonia was histologically documented 11 times in 10 patients. During the same 8-year interval, approximately 587 adults were seen at the center for a brain tumor, 90% of whom received ongoing therapy. Therefore, in at least 1.7% (10/587) of our patients with brain tumors, P carinii pneumonia developed. The median duration of dexamethasone therapy at the onset of P carinii pneumonia symptoms was 2.75 months. Symptoms began during tapering of steroid therapy in eight episodes. Bronchoscopy was diagnostic in the eight cases in which it was performed. Four episodes (40%) were fatal. Trimethoprim-sulfamethoxazole prophylaxis may be indicated in some patients with brain tumors, especially during tapering of steroid therapy.

The incidence and significance of Staphylococcus aureus in respiratory cultures from patients infected with the human immunodeficiency virus.

This study assessed the incidence and clinical significance of recovery of Staphylococcus aureus from the respiratory tract of patients infected with the human immunodeficiency virus (HIV). In a retrospective review of 129 consecutive episodes of respiratory disease in HIV-seropositive patients where respiratory tract cultures were obtained, S. aureus was recovered in 30 (23%) of the episodes. Twenty-nine of these were evaluated in this study, and the recovery of S. aureus was found to represent pneumonia in 8 cases (28%), to be of indeterminate significance in 18 cases (62%), and to represent colonization in 3 cases (10%). Episodes of S. aureus pneumonia were usually community-acquired (seven of eight episodes) and had an acute or subacute clinical presentation. Fever and physical signs of pneumonia were present in all patients. Chest radiographic presentations varied, but local infiltrates were seen in seven of eight episodes. Concomitant pulmonary disorders were common (seven of eight episodes). All patients were appropriately treated; five patients recovered and three died, giving a mortality rate of 38%. We conclude that S. aureus is a frequent isolate from respiratory tract cultures of HIV-seropositive patients referred for evaluation of pulmonary disease. It can cause a pneumonia with a high mortality rate, as it did in 6% of all episodes of pulmonary disease reviewed in this study. Clinicians should be aware that HIV-seropositive patients may develop respiratory disease secondary to S. aureus infection and that when this organism is suspected, appropriate antibiotic therapy should be instituted.

Bacterial and fungal pneumonias.

Bacterial pneumonias occur with increased frequency and can be associated with increased morbidity in the HIV-infected population compared with normals. The pathogens that most frequently cause community-acquired pneumonias are S. pneumoniae, H. influenzae, and occasionally S. aureus. These pneumonias usually respond to appropriate antibiotic therapy; however, patients diagnosed with bacterial pneumonias are at increased risk for subsequent episodes. Nosocomial pneumonias, by contrast, are usually caused by gram-negative organisms and have a high mortality. Fungal pneumonias also have an increased incidence in AIDS patients, and usually occur in the setting of disseminated disease. Infections caused by C. neoformans, H. capsulatum, and C. immitis often recur despite a good initial response to amphotericin B. Maintenance therapy with an antifungal agent is therefore recommended.

Hydrogen peroxide release by alveolar macrophages from sarcoid patients and by alveolar macrophages from normals after exposure to recombinant interferons alpha A, beta, and gamma and 1,25-dihydroxyvitamin D3.

We measured H2O2 release by human alveolar macrophages (AM) from normals and sarcoid patients in suspension immediately after bronchoalveolar lavage in the presence and absence of the triggering agent, phorbol myristate acetate (PMA). AM from 11 sarcoid patients produced a mean (+/- SE) of 21.7 +/- 2.3 and 5.9 +/- 3.4 nmol H2O2/10(6) macrophages in the presence and absence of PMA, respectively. By contrast, AM from normals (n = 6) produced 9.8 +/- 1.7 and 1.6 +/- 0.7 nmol H2O2/10(6) macrophages with and without PMA, respectively. Macrophage activation, as monitored by H2O2 production, did not correlate with the angiotensin-converting enzyme levels, the result of gallium-67 scans, or the percent of lymphocytes in the bronchoalveolar lavage. To determine whether AM from normals could be stimulated to increase their H2O2 production to the level seen in patients with sarcoid, we measured H2O2 released by adherent AM after incubation in each of four potential activating agents: recombinant interferons alpha A, beta, gamma (rIFN alpha A, rIFN beta, and rIFN gamma, respectively), and 1,25-dihydroxyvitamin D3. H2O2 release in the range seen in sarcoid patients could be induced in PMA-triggered AM from normals by rIFN gamma in a time- (t1/2 approximately 1 d) and dose-dependent fashion (threefold increase, EC50 5 antiviral U/ml) and by rIFN alpha A and rIFN beta at higher concentrations, but not by 1,25-dihydroxyvitamin D3.

Compartmentalized regulation of macrophage arachidonic acid metabolism.

We show that downregulation of arachidonic acid (20:4) metabolism which occurs following i.p. injection of C. parvum can occur in a single, localized macrophage population, and is therefore unlikely to be mediated solely by a systemic factor.

The alveolar macrophage.

The alveolar macrophage is one of the few tissue macrophage populations readily accessible to study both in the human and in animals. Since harvesting of these cells by bronchoalveolar lavage was first described in 1961, alveolar macrophages have been extensively investigated. This population is the predominant cell type within the alveolus, and undoubtedly serves as the first line of host defense against inhaled organisms and soluble and particulate molecules. Early studies focussed on this endocytic role and delineated the cells' phagocytic and microbicidal capacities. More recent investigations demonstrated an extensive synthetic and secretory repertoire including lysozyme, neutral proteases, acid hydrolases and O2 metabolites. In addition, the complex immunoregulatory role of the macrophage has also been appreciated. These cells have been shown to produce a wide variety of pro- and anti-inflammatory agents including arachidonic acid metabolites of the cyclooxygenase and lipoxygenase pathways, cytokines which modulate lymphocyte function and factors which promote fibroblast migration and replication.

Human alveolar macrophages produce leukotriene B4.

Human alveolar macrophages obtained by bronchoalveolar lavage were labeled overnight with [3H]arachidonic acid. The cells were stimulated with calcium ionophore A23187, and the 20:4 oxygenated metabolites released into the culture medium were identified by reverse-phase HPLC. Leukotriene B4 was the major 20:4 metabolite produced by these cultures. Leukotriene B4 was identified by its reverse-phase HPLC elution time, its UV spectrum, and its chemotactic and chemokinetic activities for neutrophils. In addition, the macrophage- and neutrophil-derived leukotriene B4 free acids and methyl esters were found to have identical HPLC retention times.