Acute rejection of experimental lung allografts: characterization of intravascular mononuclear leukocytes.

Leukocytes interacting with endothelia of lung allografts probably play a seminal role in acute rejection, but have not been characterized before. Transplantation was performed in the Lewis to Lewis and in the Dark Agouti to Lewis rat strain combinations. DNA replication was detected in T-cells on day 2 after pulse-labelling in vivo with 5-bromo-2'-deoxyuridine (BrdU). On day 5, leukocytes were isolated by intensive perfusion the graft, subject to flow cytometry and to quantitative RT-PCR. About 34 million leukocytes accumulated in allograft vessels, but only 10 and 6 million cells in isografts and control lungs, respectively. During rejection, IFN-gamma, IL-1beta and IL-10 mRNA expression increased, IL-12 mRNA decreased, whereas IL-2, IL-6, TNF-alpha, and TGF-beta mRNA did not change. The phenotype of graft monocytes was partially activated and intravascular T-cells proliferated. In conclusion, during rejection, monocytes with unusual properties accumulate and T-lymphocytes are activated in lung allograft blood vessels.

Macrophages in experimental rat lung isografts and allografts: infiltration and proliferation in situ.

Alveolar macrophages (AMs) and peribronchial/perivascular macrophages are probably involved in lung allograft damage. We investigate leukocyte infiltration into graft tissue and address the question whether proliferation in situ contributes to macrophage homeostasis and accumulation. Lung transplantation was performed in the Lewis (LEW)-to-LEW and in the Dark Agouti-to-LEW rat strain combination. Graft infiltration by ED1+ and ED2+ (CD163) macrophages was analyzed by immunohistochemistry (IHC) and compared with infiltration by lymphocytes. Cells in the S-phase of the cell cycle were pulse-labeled with BrdU and detected immunohistochemically. Finally, the donor or recipient origin of AMs was determined by IHC and in situ hybridization. ED1+ AMs in allogeneic transplants increased by more than 25-fold from Days 1 to 5. In addition, large, peribronchial/perivascular infiltrates developed containing numerous ED1+ cells. Although AMs in normal rat lungs are CD163-, AMs up-regulated CD163 between Days 4 and 5, reaching maximum values on Day 6. Lymphocytes were less numerous than macrophages. About 16% of the AMs and 10% of the peribronchial/perivascular macrophages were in the S-phase of the cell cycle on Day 2 post-transplantation. No differences in the frequency of BrdU+ macrophages were obvious between isografts and allografts. AMs of donor origin increased in number considerably during allograft rejection. In conclusion, the cellular infiltrate in lung allografts is dominated by macrophages, which exhibit an unusual phenotype and a strong capacity for mitotic self-renewal.

Impact of inadequate surgical antibiotic prophylaxis on perioperative outcome and length of stay on ICU in general and trauma surgery. Analysis using automated data collection.

Within surgical departments, a large amount of antibiotics is used for perioperative prophylaxis. Despite the existence of several guidelines and recommendations for administering antibiotic prophylaxis, mistakes still do occur and have an unknown impact on outcome severity. Based on the electronic anaesthesia records of 4304 patients undergoing defined surgical procedures requiring perioperative antibiotic prophylaxis, a matched pairs approach was used to evaluate the impact of inadequate antibiotic prophylaxis on hospital mortality and prolonged length of stay on intensive care. Stepwise regression models were developed to predict the impact of inadequate antibiotic prophylaxis on outcome measures. An inadequate antibiotic prophylaxis was found for a total of 877 cases. 77.9% of cases were successfully matched, leading to 683 cases and controls each. The crude mortality ratio of cases to controls was 1.5 (cases = 21 versus controls = 14; P = 0.19). The case group had a significantly (P < 0.01) prolonged stay on ICU when analysed as a metric variable. Using logistic regression analysis, we could determine that inadequate antibiotic prophylaxis had no impact on either hospital mortality or prolonged length of stay on ICU (>1 day; yes or no).