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Biomedical subjects

C J Schleupner

Publications and source records attributed to C J Schleupner.

9 recordsLinked to original sources

A study of the etiologies and treatment of nosocomial pneumonia in a community-based teaching hospital.

OBJECTIVE: To compare the frequency of the pathogens of nosocomial pneumonia in a community-based teaching hospital to the frequencies previously published, and to evaluate recommendations for the therapy of nosocomial pneumonia in this setting. DESIGN: Retrospective review of prospectively acquired data accrued during 9 randomized single-blinded and 4 single-agent investigational antibiotic studies for the therapy of pneumonia in hospitalized patients between 1981 and 1989. SETTING: The study was performed at a university affiliated, community-based teaching Department of Veterans Affairs Medical Center. PATIENTS: Patients were hospitalized on the acute medical/surgical and intermediate medicine wards. Informed consent was obtained prior to enrolling patients into the respective antimicrobial studies. Pneumonia was documented radiographically and clinically for each patient. RESULTS: Two hundred thirty-one episodes of nosocomial pneumonia were treated. Overall, 51% of pneumonias were caused by Streptococcus pneumoniae or Hemophilus influenzae with or without other organisms that were not gram-negative bacilli. Gram-negative bacilli, with or without other organisms, accounted for only 26% of all nosocomial pneumonias. Overall, monotherapy with a cephalosporin (usually a broad-spectrum agent) was equally efficacious compared with combination therapy (87% versus 81%, respectively). Cure rates for nosocomial pneumonias from gram-negative bacilli treated with these 2 therapies also were similar (70% versus 60%, respectively). CONCLUSIONS: In nontertiary care settings, gram-negative bacilli may cause fewer episodes of nosocomial pneumonia (26% in this study) than noted by previously published reports, which indicated that these organisms account for 50% of nosocomial pneumonias. Further, S pneumoniae and H influenzae may account etiologically for many of these nosocomial pneumonias. Monotherapy with an extended-spectrum cephalosporin may be more appropriate than combined treatment with a beta-lactam and an aminoglycoside in a nontertiary care setting, thereby reducing potential toxicity in an older, hospitalized patient population.

Adult

Infectious mononucleosis and Epstein-Barr virus. 1. Epidemiology, pathogenesis, immune response.

The evidence linking Epstein-Barr virus causally with infectious mononucleosis is compelling. The disease occurs only in persons who lack antibody to this virus, and serologic findings during the acute illness provide almost certain evidence for its etiologic association. Additional evidence is derived from transformation studies using lymphocytes from persons infected with Epstein-Barr virus. Epidemiologic studies have related the need for close contact with salivary secretions to the low communicability of infectious mononucleosis. The clinically relevant antibodies which develop during the disease, other than heterophile antibody, are those against the viral capsid antigen. Part 2 of this article considers the clinical picture, diagnosis, and management and begins on page 95.

Acute Disease

Infectious mononucleosis and Epstein-Barr virus. 2. Clinical picture, diagnosis, management.

The diagnosis of infectious mononucleosis is confirmed by hematologic, biochemical, and serologic data. An absolute increase in peripheral mononuclear cells to at least 4,500/cu mm is an essential feature. The serologic hallmark of the disease is the presence of heterophile antibody. The age of the patient may affect the clinical presentation and laboratory findings. Therapy is largely supportive, with steroids being used only in the presence of certain severe complications.

Adolescent

Activation of reticuloendothelial cells following infection with murine cytomegalovirus.

Macrophage and reticuloendothelial system function was investigated in adult, female C3H mice during the course of a nonlethal infection with murine cytomegalovirus (MCMV). Peritoneal macrophages harvested from mice infected three to 21 days previously were tumoricidal in vitro for a syngeneic mammary tumor cell line and showed antiviral activity by suppressing replication of vaccinia virus in a fibroblast monolayer. In addition, macrophages harvested from animals on days 7 and 14 after MCMV infection manifested augmented phagocytosis of yeast particles in vitro. Furthermore, enhanced levels of chemiluminescence were emitted during phagocytosis of zymosan particles by macrophages harvested on days 3 and 7 after MCMV infection. Finally, enhanced protection against Listeria monocytogenes was demonstrated in mice on days 7, 14, and 21 after MCMV infection. These findings support the concept of activation of the reticuloendothelial system during viral infection.

Animals

Enhancement of resistance to murine osteogenic sarcoma in vivo by an extract of Brucella abortus (Bru-Pel): association with activation of reticuloendothelial system macrophages.

The administration of an aqueous-ether extracted residue of Brucella abortus (Bru-Pel) inhibits development of transplanted osteogenic sarcomas in mice as evidenced by a decrease in mortality. At least one mechanism through which Bru-Pel modulates host resistance is activation of macrophages of the reticuloendothelial system. Peritoneal macrophages harvested from mice receiving Bru-Pel were cytotoxic for osteogenic sarcoma cells in vitro, limited the replication of vaccinia virus in cell cultures, and demonstrated enhanced emittance of chemiluminescence during phagocytosis of zymosan particles of Candida albicans. The concept of reticuloendothelial system activation was further supported by the evidence that administration of Bru-Pel enhanced resistance of mice to challenge with a lethal inoculum of Listeria monocytogenes. These observation support the hypothesis that Bru-Pel shares a number of characteristics with recognized immunomodulating agents and that one mechanism by which it modulates host resistance to tumors, to virus infections, and to challenge with L. monocytogenes is through activation of macrophages.

Animals

Severity of underlying disease as a predictor of nosocomial infection. Utility in the control of nosocomial infection.

In a prospective study, we determined that severity of underlying disease at time of admission indicates medical patients at unusual risk of nosocomial infection. The nosocomial infection rate was 23.6% in patients with fatal underlying disease, 9.6% in those with ultimately fatal disease, and 2.1% in those with nonfatal disease. After an awareness program that promoted the use of established methods for prevention of nosocomial infections was established, there was a decline of overall incidence of endemic nosocomial infections from 9.2% to 4.8% (P less than .001) within an eight-month period. With subsequent discontinuation of the program, the infection rate rose to 8.1%. Reinstitution of the program resulted in a decline to 5.2% (P = .05).

Cross Infection

Peritoneal macrophage activation indicated by enhanced chemiluminescence.

A number of studies have demonstrated the ability of various bacterial preparations, protozoa, and chemicals to activate macrophages and concomitantly to enhance host resistance to both tumors and infections. Recently, viral infections have been shown to have a similar effect upon macrophage function. To better define the metabolic state of activated macrophages, we have evaluated the ability of peritoneal cells (PC) from vaccinia virus- or murine cytomegalovirus-infected or Corynebacterium parvum-treated mice to emit chemiluminescence (CL) during phagocytosis of zymosan particles or yeasts. PC from C. parvum-treated mice (1,400 microgram intraperitoneally) emitted enhanced CL over controls on days 3, 6, 14, and 21 after treatment, thereby establishing the emission of CL as a correlate of metabolic activation. Previous evidence for activation of PC from vaccinia virus-infected mice (10(8) plaque-forming units) was confirmed by demonstration of enhanced levels of CL on days 3, 6, and 13 after murine infection. Likewise, PC from mice infected with murine cytomegalovirus (10(5) plaque-forming units) 3, 6, or 13 days previously demonstrated augmented levels of CL over controls. Opsonized virus particles (vaccinia virus or murine cytomegalovirus) failed to induce the emission of CL with PC from mice infected with the isologous virus. Our data further demonstrate the immunomodulationinduced by virus infections and suggest that the detection of CL is an easily quantitated correlate of macrophage activation which may be helpful in defining metabolic alterations induced during activation.

Animals

Activation of reticuloendothelial system macrophages and enhancement of host resistance to a transplantable osteogenic sarcoma in mice by an extract of Brucella abortus.

An aqueous-ether extract of Brucella abortus, Bru-Pel, enhanced resistance of mice to a transplantable osteogenic sarcoma (OGS). The results presented in this report suggest that Bru-Pel is an effective immunomodulator and that one mechanism through which it enhances host resistance is activation of phagocytic cells of the reticuloendothelial system. Peritoneal macrophages from mice inoculated with Bru-Pel 14 days previously were cytotoxic for OGS cells in vitro, limited the multiplication of vaccinia virus in cell cultures, and demonstrated increased chemiluminescence during phagocytosis. Furthermore, Bru-Pel enhanced host resistance to Listeria monocytogenes, in addition to viral infections and a transplantable tumor. These results support the hypothesis that Bru-Pel shares a number of characteristics with other recognized immunomodulating agents and suggest that further studies are warranted to better define the potential of Bru-Pel for immunotherapeutic regimens in man.

Animals