Utility of bronchoscopy with bronchoalveolar lavage in diagnosing pulmonary infection in hospitalized patients with underlying malignancy.

OBJECTIVES: To evaluate the clinical utility of bronchoscopy with bronchoalveolar lavage (BAL) for diagnosing pulmonary infection in patients with underlying malignancy and to evaluate the impact of positive microbiology results on antimicrobial therapy. DESIGN: Retrospective chart review. SETTING: University-affiliated downtown teaching hospital in Toronto. PATIENT POPULATION: All patients who underwent bronchoscopy with BAL from November 1990 to September 1992. RESULTS: One hundred and thirty-nine BALs were performed, of which 82 (59%) were positive for microorganisms. These 82 charts were reviewed. The main underlying diagnosis was hemotogenous malignancy (70 of 82). Primary indiction for bronchoscopy was the presence of pulmonary symptoms with or without radiographic abnormality. Common organisms identified were fungi (n=50), primarily Candida albicans and cytomegalovirus (CMV) (27), and 16 'usual' pathogens. Less common were herpes simplex virus (six), Pneumoncystis carinii pneumonia (PCP) (four), Legionella pneumoniae and Mycoplasma pneumoniae (one each). Eighty-seven per cent of patients were on broad spectrum antibiotics at the time of bronchoscopy. Although antiibiotic therapy was altered postbronchoscopy in 47 of the 82 cases, only 26 instances could be directly attributed to the results of BAL. Pathogens that commonly initiated specific therapy were CMV (16 of 27) and PCP (three of four). Diagnostic yield was highest in allogenic bone marrow transplant recipients (BMT). They comprised only 49% (40 of 82) of the cases but accounted for 85% (22 of 26) of those whose therapy was directly altered by the results of BAL. Of these 22 cases, 20 were attributed to the isolation of CMV. CONCLUSIONS: The overall raw diagnostic yield from bronchoscopy with BAL was high at 59%. Of those with positive BAL cultures, a change in antimicrobial management occurred in 32% of cases. In a patient poulation with underlying hematogenous malignancy, particularly BMT recipients, bronchoscopy with BAL is useful for a specfic diagnosis of pulmonary infection.

Long-term sequelae after recovery from cytomegalovirus pneumonia in allogeneic bone marrow transplant recipients.

The clinical course of cytomegalovirus (CMV) pneumonia in seven consecutive bone marrow transplant (BMT) recipients during a 24-month period was studied. Retrospective analysis of clinical data on the recipients with CMV pneumonia during the illness and prospective follow-up of those who recovered from the pneumonia was performed. Those who had CMV as the sole pathogen and with lymphocytosis in the BAL or the peripheral blood during the illness recovered from the pneumonia. On the contrary, those who had mixed bacterial or fungal infection with peripheral lymphopenia died. Persistent lymphocytosis in the BAL and the peripheral blood, in the absence of CMV infection, was observed in the survivors. Two subsequently developed restrictive lung disease and two had relapse of their primary malignancy. These data suggest that CMV pneumonia in BMT patients is associated with significant long-term sequelae. The phenomenon of persistent lymphocytosis in the BAL and the peripheral blood, in the absence of CMV infection, supports Grundy's hypothesis that CMV pneumonia in BMT recipients is an immunopathologic condition.

Norwalk-like gastroenteritis epidemic in a Toronto hospital.

An epidemic of gastroenteritis in a teaching hospital affected 57 patients and 69 staff over a 26-day period. The index case was a patient admitted with acute abdominal pain and diarrhea two days prior to the outbreak. The epidemic curve indicated person-to-person transmission. The incubation period, duration and types of symptoms were typical of Norwalk gastroenteritis, and Norwalk-like virus particles, serologically different from the prototype Norwalk virus strain, were observed in 17 of 20 fecal specimens examined by immune-electron microscopy.

Clinical evaluation of the Ortho Rubella ELISA Test System.

The Ortho Rubella ELISA Test System (Ortho Diagnostics Canada Ltd., Toronto, Ontario) is an enzyme-linked immunosorbent assay (ELISA) for the determination of IgG antibodies to rubella virus. Comparison of the Ortho Rubella ELISA with a commercial hemagglutination inhibition (HAI) test revealed that the ELISA is well suited for routine use as a qualitative screening test for rubella immune status or the demonstration of seroconversions. Quantitation of rubella antibodies by the Ortho Rubella ELISA, however, requires that ELISA endpoint determination be made on serial serum dilutions.

Presumed respiratory syncytial virus pneumonia in three immunocompromised adults.

Three cases of presumed respiratory syncytial virus (RSV) pneumonia in immunocompromised adults are described. Two patients had symptoms of cough, fever, and malaise, following completion of a course of combination chemotherapy for the treatment of acute lymphoblastic leukemia. The third patient, a juvenile onset diabetic, developed similar symptoms while hospitalized for severe hyperglycemia. Chest roentgenograms showed lower lobe infiltrates in both leukemic patients and a bilateral non-confluent bronchopneumonia in the diabetic patient. All patients had a marked rise in complement-fixing antibody titres to RSV, suggesting a concurrent infection with the virus. Extensive microbiological investigations failed to reveal any other etiologic agent. Nosocomial infection was considered possible. RSV is not considered a cause of pneumonia in compromised adults. Our three cases suggest that there may be a higher incidence of RSV pneumonia in compromised patients, than previously recognized.

DNA binding of a nonstructural reovirus protein.

The specific early inhibition of DNA synthesis in reovirus-infected cells suggests that the cell nucleus is a target for virus-induced damage. We have now examined the affinity of reovirus proteins for DNA, postulating that such affinity could provide a mechanism for the inhibition. Cytoplasmic and nuclear extracts of cells labeled with [35S] methionine from 6 to 8.5 h after infection at high multiplicity was subjected to chromatography on denatured DNA - cellulose columns. Fractions from both cytoplasm and nucleus eluted with 0.6 N NaCl contained a protein with the same electrophoretic mobility of polyacrylamide slab gels as the nonstructural (NS) reovirus protein of the sigma size class. The protein also exhibited affinity for native DNA - cellulose and denatured DNA - agarose. Electrophoretic analysis is tube gels of cell extracts labeled for 48 h before infection with [14C] leucine and from 6 to 8.5 h after infection with [3H] leucine showed increased 3H label in this protein indicating it is reovirus specific. Small amounts of mu proteins also had DNA affinity. Purified virus did not bind strongly to DNA, suggesting that the binding protein is not a structural protein of the sigma size class on the outer surface of the virus. Our results provide evidence that the sigma NS protein binds to DNA. This affinity could interfere with chromosome function in the infected cell.

DNA and histone synthesis in reovirus-infected cells.

Reovirus infection inhibits the incorporation of 3H-thymidine into cellular DNA. We have now investigated several aspects of this inhibition in L-929 cells early (8 h) after infection at high multiplicity (200 to 250 p.f.u./cell). Using equilibrium sedimentation analysis of DNA sequentially labelled with density and radioactive analogues of thymidine, we find a 52% reduction in the amount of DNA synthesized with no change in rate of replication fork movement in infected cells. Gel electrophoresis of histones labelled with 3H-lysine shows that infection inhibits their synthesis by 76% several hours before overall cellular protein synthesis is inhibited. There is also a reduction of nearly 50% in the size of the thymidine triphosphate pool, as measured by enzymic assay. The proportion of exogenous nucleotide in the pool is the same as in uninfected cells since there is no change in the buoyant density of DNA labelled during a short pulse with 3H-bromodeoxyuridine. The uptake of thymidine is reduced, but its phosphorylation to thymidine triphosphate is normal. The findings provide direct evidence that DNA synthesis is inhibited early in infection. This inhibition is accompanied by other derangements of thymidine and chromatin metabolism suggesting that there is an early and specific attack by reovirus on nuclear function in infected cells.