Search PubMed⌕ Search

Biomedical subjects

Christian Brun-Buisson

Publications and source records attributed to Christian Brun-Buisson.

58 records · Page 4Linked to original sources

Exacerbation by granulocyte colony-stimulating factor of prior acute lung injury: implication of neutrophils.

OBJECTIVE: Granulocyte colony-stimulating factor is widely prescribed to hasten recovery from cancer chemotherapy-induced neutropenia and has been reported to induce pulmonary toxicity. However, circumstances and mechanisms of this toxicity remain poorly known. DESIGN: To reproduce a routine situation in cancer patients receiving chemotherapy, we investigated the mechanisms underlying granulocyte colony-stimulating factor-induced exacerbation of alpha-naphthylthiourea-related pulmonary edema. SETTING: Laboratory research unit. SUBJECTS: Male specific-pathogen-free Sprague-Dawley rats. INTERVENTIONS: The effects of granulocyte colony-stimulating factor given alone or after alpha-naphthylthiourea used to induce acute lung injury were investigated. MEASUREMENTS AND MAIN RESULTS: Lung injury was assessed based on neutrophil sequestration (myeloperoxidase activity in lung tissue) and influx into alveolar spaces (bronchoalveolar lavage fluid cell quantification) and on edema formation (wet/dry lung weight ratio) and alveolar protein concentration into bronchoalveolar lavage fluid. Tumor necrosis factor-alpha and interleukin-1beta were measured in serum, lung homogenates, and isolated alveolar macrophage supernatants. In control rats, granulocyte colony-stimulating factor (25 microg/kg) significantly elevated circulating neutrophil counts without producing alveolar recruitment or pulmonary edema. alpha-Naphthylthiourea significantly increased the wet/dry lung weight ratio (4.68 +/- 0.04 vs. 4.38 +/- 0.07 in controls, p=.04) and induced alveolar protein leakage. Adding granulocyte colony-stimulating factor to alpha-naphthylthiourea exacerbated pulmonary edema, causing neutrophil sequestration in pulmonary vessels, significantly increasing lung myeloperoxidase activity (12.7 +/- 2.0 mOD/min/g vs. 1.1 +/- 0.4 mOD/min/g with alpha-naphthylthiourea alone; p<.0001), and increasing proinflammatory cytokine secretion. alpha-Naphthylthiourea-related pulmonary edema was not exacerbated by granulocyte colony-stimulating factor during cyclophosphamide-induced neutropenia or after lidocaine, which antagonizes neutrophil adhesion to endothelial cells. Tumor necrosis factor-alpha and interleukin-1beta concentrations in alveolar macrophage supernatants and lung homogenates were significantly higher with alpha-naphthylthiourea + granulocyte colony-stimulating factor than with either agent alone, and anti-tumor necrosis factor-alpha antibodies abolished granulocyte colony-stimulating factor-related exacerbation of alpha-naphthylthiourea-induced pulmonary edema. In rats with cyclophosphamide-induced neutropenia, tumor necrosis factor-alpha concentrations in alveolar macrophage supernatants and lung homogenates were significantly decreased compared with rats without neutropenia. CONCLUSION: Granulocyte colony-stimulating factor-related pulmonary toxicity may involve migration of neutrophils to vascular spaces, adhesion of neutrophils to previously injured endothelial cells, and potentiation of proinflammatory cytokine expression.

Animals↗

Outpatient antibiotic use and prevalence of antibiotic-resistant pneumococci in France and Germany: a sociocultural perspective.

The prevalence of penicillin-nonsusceptible pneumococci is sharply divided between France (43%) and Germany (7%). These differences may be explained on different levels: antibiotic-prescribing practices for respiratory tract infections; patient-demand factors and health-belief differences; social determinants, including differing child-care practices; and differences in regulatory practices. Understanding these determinants is crucial for the success of possible interventions. Finally, we emphasize the overarching importance of a sociocultural approach to preventing antibiotic resistance in the community.

Ambulatory Care↗

Epidemiology of sepsis and infection in ICU patients from an international multicentre cohort study.

OBJECTIVES: To examine the incidence of infections and to describe them and their outcome in intensive care unit (ICU) patients. DESIGN AND SETTING: International prospective cohort study in which all patients admitted to the 28 participating units in eight countries between May 1997 and May 1998 were followed until hospital discharge. PATIENTS: A total of 14,364 patients were admitted to the ICUs, 6011 of whom stayed less than 24 h and 8353 more than 24 h. RESULTS: Overall 3034 infectious episodes were recorded at ICU admission (crude incidence: 21.1%). In ICU patients hospitalised longer than 24 h there were 1581 infectious episodes (crude incidence: 18.9%) including 713 (45%) in patients already infected at ICU admission. These rates varied between ICUs. Respiratory, digestive, urinary tracts, and primary bloodstream infections represented about 80% of all sites. Hospital-acquired and ICU-acquired infections were documented more frequently microbiologically than community-acquired infections (71% and 86%, respectively vs. 55%). About 28% of infections were associated with sepsis, 24% with severe sepsis and 30% with septic shock, and 18% were not classified. Crude hospital mortality rates ranged from 16.9% in non-infected patients to 53.6% in patients with hospital-acquired infections at the time of ICU admission and acquiring infection during the ICU stay. CONCLUSIONS: The crude incidence of ICU infections remains high, although the rate varies between ICUs and patient subsets, illustrating the added burden of nosocomial infections in the use of ICU resources.

Canada↗