Lung Donation After Controlled Circulatory Determination of Death: A Review of Current Practices and Outcomes.

BACKGROUND: Since the first reported series in 1995, transplantation of lungs recovered through donation after circulatory determination of death (DCDD) has steadily increased. In some European and Australian centers, controlled DCDD accounts for 15% to 30% of all transplanted lungs. Several transplant centers have reported early and midterm outcomes similar to those associated with the use of donors after brain death. Despite these encouraging reports, less than 2% of all lung transplants in the United States are performed using donors after circulatory determination of death. METHODS: An electronic search from January 1990 to January 2014 was performed to identify series reporting lung transplant outcomes using controlled DCDD. Data from these publications were analyzed in terms of donor characteristics, donation after circulatory determination of death protocols, recipients' characteristics, and early and midterm outcomes. RESULTS: Two hundred twenty-two DCDDs were transplanted into 225 recipients. The rate of primary graft dysfunction grade 3 ranged from 3% to 36%. The need for extracorporeal membrane oxygenation support after transplantation ranged from 0% to 18%. The average intensive care unit stay ranged from 4 to 8.5 days and the average hospital stay ranged from 14 to 35 days. Thirty-day mortality ranged from 0% to 11% and 1-year survival from 88% to 100%. CONCLUSION: Under clinical protocols developed and strictly applied by several experienced lung transplant programs, lungs from controlled DCDD have produced outcomes very similar to those observed with brain death donors.

Antigen specificity of antibody responses to Corynebacterium pseudotuberculosis in naturally infected sheep with caseous lymphadenitis.

Constituents of Corynebacterium pseudotuberculosis were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Analysis of sonicated whole bacterial cells and ether-extracted cells revealed more than 35 bands in silver-stained gels. SDS-PAGE analysis of concentrated culture filtrates with exotoxin activity demonstrated more than 15 bands. Sera from sheep with C. pseudotuberculosis-induced disease of variable severity were used to probe immunoblots of electrophoresed ether-extracted cells and culture filtrates. Twenty or more corynebacterial molecules, ranging in molecular weight from 20 to 112 kDa, in ether-extracted cells were recognized by antibodies in the sera of naturally exposed sheep with positive ELISA titers. These sera also recognized up to six molecules, ranging from, 20 to 68.1 kDa, on immunoblots of ammonium sulfate-concentrated culture filtrate. There was no apparent relationship between the stage of disease and the response to specific corynebacterial antigens in these animals.

Antigen specificity and activity of ovine antibodies induced by immunization with Corynebacterium pseudotuberculosis culture filtrate.

Sheep were immunized three times with a vaccine composed of filtrate from a 36 h culture of Corynebacterium pseudotuberculosis and a block polymer adjuvant. Immunization resulted in the development of exotoxin-neutralizing antibody. This corresponded to the recognition of a 31.6 kDa protein on sequential immunoblots of ammonium sulfate-precipitated filtrate. In addition sera from vaccinated sheep recognized at least eight bacterial cellular antigens on immunoblots of ether-extracted C. pseudotuberculosis, including bands of 12, 25.1, 31.6, 36.3, 39.8, 63.1, 70, 75 or 79.4 kDa. Sera from these sheep altered the colony growth characteristics of C. pseudotuberculosis in vitro. These results indicate that immunization with soluble C. pseudotuberculosis in vitro. These results indicate that immunization with soluble C. pseudotuberculosis antigen preparations that have been used in toxoid vaccines induces antibody responses to numerous cellular antigens in addition to exotoxin and suggest that serologically mediated antibacterial effects could be an important component in the protection from disease that has been reported following immunization with C. pseudotuberculosis toxoids.

Differential antibody responses to Corynebacterium pseudotuberculosis in sheep with naturally acquired caseous lymphadenitis.

Enzyme-linked immunosorbent assays (ELISA) with Corynebacterium pseudotuberculosis cell wall and bacteria-free supernatant with exotoxin preparations as antigens, and hemolysis inhibition tests were used to detect antibodies in the sera of adult range sheep with naturally acquired caseous lymphadenitis (CL). The extent and severity of lesions were quantitated on the basis of a lesion score, derived from an examination of the carcass (peripheral lymphoid tissue) and viscera (including internal lymphoid tissue) at the time of slaughter. The overall prevalence of C pseudotuberculosis-positive CL lesions in 104 sheep was 31.7%. The cell wall ELISA detected antibodies in 96.9% (32/33) of sheep with C pseudotuberculosis-positive CL lesions. The exotoxin ELISA detected antibodies in 84.8% (28/33) of positive sheep in the same group. Both ELISA resulted in a high number of apparent false-positives, with 64.7% and 49.2%, respectively, positive optical density (OD) values in sheep with no gross CL lesions and no apparent C pseudotuberculosis infection. There was no significant relationship between the extent of lesion development (lesion score) and OD values in both cell wall (r = 0.472) and exotoxin (r = 0.464) ELISA. Similarly, there was no significant relationship between the titer of antitoxin antibodies, as measured by the hemolysis inhibition test, and the extent of disease. These investigations indicate that those ELISA that use crude C pseudotuberculosis antigens are of questionable utility in the field, where C pseudotuberculosis infection is endemic in many sheep populations. Furthermore, these studies suggest that antibodies that are reactive with components of C pseudotuberculosis and that develop in response to infection may have little impact on the recovery of the host.

Clinical and immunologic response of cattle to administration of a vaccine containing modified-live bovine respiratory syncytial virus.

Healthy yearling beef and dairy cattle were inoculated with a vaccine containing modified-live bovine respiratory syncytial virus (ML-BRSV), and sequential changes in clinical signs of disease, blood leukocyte subsets, BRSV-specific antibody titer, and in vitro lymphocyte blastogenic responses were monitored. Vaccination with ML-BRSV did not cause pyrexia, local or systemic hypersensitivity reaction, or respiratory tract disease. Episodes of leukopenia, abnormalities in lymphocyte subsets, or depression of phytomitogen-induced blastogenic responses were not observed subsequent to vaccination. Exposure to ML-BRSV resulted in at least a 16-fold increase in serum neutralizing antibody titer, with no increase seen in nonvaccinated contact controls. Significant BRSV-specific lymphocyte blastogenic responses were not detected, using one dose of several BRSV antigen preparations in a whole blood culturing system.

T lymphocyte subset alterations following bluetongue virus infection in sheep and cattle.

To determine potential mechanisms of differential disease expression in ruminants infected with bluetongue virus (BTV), clinically normal, BTV-seronegative, yearling sheep and cattle were infected subcutaneously with a standardized insect-source inoculum of BTV serotype 17 (BTV-17) (three infected and one contact control each) or animal adapted BTV serotype 10 (BTV-10) (three sheep only). BTV was isolated from peripheral blood cell components of infected sheep and cattle and all infected animals showed evidence of seroconversion by 14 days post infection (PI). Sheep infected with both serotypes of BTV developed pyrexia, oral lesions, and leukopenia which were most severe on days 7-8 PI. Analysis of peripheral blood mononuclear leukocytes with specific monoclonal antibodies and flow cytometry revealed panlymphocytopenia on day 7 PI. This response was further characterized by an increase in the CD4/CD8 ratio (greater than 3) resultant from a greater decrease in absolute numbers of circulating SBU-T8(CD8+) ("cytotoxic/suppressor") lymphocytes compared to SBU-T4 (CD4)+ ("helper") lymphocytes. SBU-T19+ lymphocytes were also decreased below baseline values on days 5-14 post infection. On day 14 PI there were increased CD8+ lymphocytes and decreased CD4/CD8 ratios (approximately 0.6) in these sheep. Clinical and hematologic changes in cattle infected with BTV-17 were minimal and consisted of mild pyrexia (rectal temperature 103 degrees F) on day 9 PI in two of three infected animals and mild leukopenia on several days PI in one animal. This leukopenia was the result of a pan T lymphocytopenia with CD4/CD8 ratios in the expected range (1-2). Similar to infected sheep, infected cattle did have a shift (decrease, approximately 0.8) in the peripheral CD4/CD8 ratio associated with an increase in circulating BoT8 (CD8)+ lymphocytes on day 14 post infection. Lymphocytes in the peripheral blood of all sheep and cattle infected with BTV-17 proliferated in vitro in response to purified BTV-17. These results confirm and extend those of previous studies that indicate species differences in the hematologic response to an equivalent BTV infection in domestic ruminants.

Flow cytofluorimetric analysis of lymphocyte subset alterations in cattle infected with bovine viral diarrhea virus.

Clinically normal, bovine viral diarrhea virus (BVDV)-seronegative, 7 to 9-month-old steers were inoculated intranasally with NY-1, a noncytopathic strain of BVDV, or exposed intramuscularly to killed BVDV. Indirect immunofluorescence staining with monoclonal antibodies specific for bovine leukocyte subsets followed by flow cytometric analysis was used to monitor subsequent hematologic alterations. Infection with BVDV resulted in a transient leukopenia which was characterized by decreases in the absolute numbers of circulating T lymphocytes, including BoT4+ ("helper") and BoT8+ ("cytotoxic/suppressor") subsets, B lymphocytes, and neutrophils. There was no significant variation in numbers of non-T, non-B ("null") lymphocytes or monocytes. Exposure to inactivated BVDV in a combination vaccine did not cause significant alteration in the circulating numbers of any major leukocyte subset; however, significant variation was seen in the BoT4/BoT8 ratios and in the numbers of cells expressing major histocompatibility complex (MHC) class II antigens.