Screening donors for xenotransplantation: The potential for xenozoonoses

Xenotransplantation is a potential solution to the current donor shortage for solid organ transplantation. The transmission of infectious agents from donor organs or bone marrow to the recipient is a well-recognized phenomenon following allotransplantation. Thus the prospect of xenotransplantation raises the issue of xenozoonoses-i.e., the transmission of animal infections to the human host. Anticipating an increasing number of baboon to human transplants, 31 adult male baboons (Papio cynocephalus) from a single colony in the United States were screened for the presence of antibody to microbial agents (principally viral) that may pose a significant risk of infection. Antibody to simian cytomegalovirus, simian agent 8 and Epstein-Barr virus, was found in 97% of animals tested. Antibody to simian retroviruses and Toxoplasma gondii was found in 30% and 32% respectively. Discordant results were found when paired samples were examined by two primate laboratories. This was particularly noted when methodologies were based on cross-reaction with human viral antigens. These results highlight the need to develop specific antibody tests against the species used for xenotransplantation. © 1994 Williams & Wilkins

Combined transplantation of the heart and liver

The technique of combined transplantation of the heart and liver is described and illustrated, emphasizing modifications that were used in a successful case. Two other unsuccessful attempts are reported, and the importance of relative size of donor and recipient is discussed. There may be an immunological advantage to transplanting two organs in combination from the same donor

Cardiac transplantation with cyclosporin A and prednisone

Influenced by continuing improvement in results from Stanford, cardiac transplantation was resumed at the University Health Center of Pittsburgh in June 1980. Cyclosporin A (CyA) became available to the authors early in 1981. This report describes the preliminary experience with 21 patients who were treated between March 1981 and April 10, 1982 with cyclosporin A and low-dose steroids. Ages ranged from eight to 53 years, median 46 years. Median age of ten patients disabled because of idiopathic myocardiopathy was 33 years; it was 45 years in the 11 suffering from ischemic heart disease. Sixteen of the 21 patients survived. Eleven have survived for three months, of which six have survived for six months, giving a cumulative survival of 74 and 66%, respectively. Four died perioperatively; one died at six weeks and one at four months. Hyperacute rejection resulted in one death at 12 hours even though the warm and cold lymphocytotoxic crossmatch for T and B cells was negative as evaluated by trypan blue. The two late deaths were related to infection. No late death has occurred because of rejection, and a unique feature is that three recipients with a lymphocytotoxic mismatch did not develop hyperacute rejection. The number of infectious episodes and nonviral infections appears to be less than that associated with the use of azathiaprine and larger doses of steroids. Cyclosporin A (5-10 mg/kg/d) and low-dose prednisone (rapidly tapered in seven days from 200 mg to 15-20 mg/d) is effective in preventing early morbid rejection of the transplanted heart

Liver Allograft: Its Use in Chronic Active Hepatitis with Macronodular Cirrhosis, Hepatitis B Surface Antigen

A patient suffering from chronic active hepatitis with macronodular cirrhosis, positive for hepatitis B surface antigen (HBsAg), was treated with an orthotopic liver allograft. The HBs antigenemia, as measured with several precipitation tests and by complement fixation, became negative after transplantation and remained so for about 2½ months. During the interval, very low titers of the antigen were detectable by radioimmunoassay. At about three months after transplantation, she had an attack of acute hepatitis, at which time HBsAg became detectable by all tests. She recovered, but progressive liver disease developed during the remaining 1½ years of her life. She died of disseminated nocardiosis and candidiasis with deteriorating hepatic function. The homograft at autopsy showed no evidence of rejection, but was the site of chronic active liver disease, although of a different pathologic pattern than that affecting her native liver. The differences in histology may reflect the influence of chronic immunosuppression on the features of chronic active hepatitis. © 1979, American Medical Association. All rights reserved

Liquid chromatography-tandem mass spectrometry - Application in the clinical laboratory

This review provides a concise survey of liquid chromatography tandem mass spectrometry (LCTMS) as an emerging technology in clinical chemistry. The combination of two mass spectrometers with an interposed collision cell characterizes LCTMS as an analytical technology on its own and not just as a more specific detector for HPLC compared with conventional techniques. In LCTMS, liquid chromatography is rather used for sample preparation but not for complete resolution of compounds of interest. The instrument technology of LCTMS is complex and comparatively expensive; however, in routine use, methods are far more rugged compared to conventional chromatographic techniques and enable highthroughput analyses with very limited manual handling steps. Moreover, compared to both gas chromatographymass spectrometry (GCMS) and conventional HPLC techniques, LCTMS is substantially more versatile with respect to the spectrum of analyzable compounds. For these reasons it is likely that LCTMS will gain far more widespread use in the clinical laboratory than HPLC and GCMS ever did. In this article, the key features of LCTMS are described, method development is explained, typical fields of application are discussed, and personal experiences are related

Techniques for combined procurement of hearts and kidneys with satisfactory early function of renal allografts.

Methods for combination of donor nephrectomy with donor cardiectomy are outlined. The satisfactory early function of 29 of 34 transplanted kidneys harvested with these techniques supports their wider application and should encourage their wider acceptance

Factors associated with invasive lung aspergillosis and the significance of positive aspergillus culture after liver transplantation

From January 1981 to December 1990, 2180 patients underwent orthotopic liver transplantation at the University of Pittsburgh. Thirty-two patients (1.5%) were identified with invasive aspergillosis (29 lung, 2 intraabdominal, 1 meningitis). Of 29 patients with invasive lung disease, only 23 (79%) had positive culture (Aspergillus fumigatus, 20; Aspergillus flavus, 3). Forty-eight variables were analyzed and compared in 23 patients with invasive disease with positive cultures and 9 patients with colonization only. The variables associated with pulmonary invasive disease, by univariate analysis, were surgical time (P =.03), presence of laparotomies (P =.02), higher creatinine level at time of Aspergillus isolation (P =.01), and use of OKT3 (P =.02). However, in a multivariate analysis, only the last two (creatinine, OKT3) were associated with invasive lung aspergillosis. Of 4 patients with positive abdominal wound culture, 2 had local invasive aspergillosis. Therefore, positive cultures of Aspergillus organisms from respiratory secretions and wound drainage may represent invasive disease and should not be ignored. © 1992 the University of Chicago