Three-day hypothermic storage of canine lungs.
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Biomedical subjects
Publications and source records attributed to R M Condie.
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101 first transplants were done in patients with end-stage renal disease using kidneys from parents or offspring. All patients were followed up for at least two years, and the absolute two-year patient-survival rate was 88% and the two-year functional-kidney rate was 79%. Actuarial statistics at four years were 82% for survival and 67% for function in the parent-to-child group. In the child-to-parent group absolute patient survival was 83% and transplant function was 79% at two years; these results were unchanged at four years. Thus, transplants from parents to children or from children to parents are much the same despite differences in age. There is some advantage in parent-to-child transplants from being female but no advantage in being diabetic, receiving higher or lower doses of antilymphocyte globulin, or sharing more than two HLA antigens with the donor. Mismatched sibling transplants survived approximately as well as did grafts from parents to children and children to parents. These results, taken in concert with the poor results of cadaver transplantation, the relative safety of donation, the high personal motivation to donate in these groups, and the personal satisfaction derived by the donor, strongly support the policy of informing potential recipients of the benefits of parental or offspring kidney donation.
Antibody of the IgGab type can be isolated from horses immunized with cultured human lymphoblasts plus complete Freund's adjuvant. The essential steps for the production of a safe, potent anti-human lymphoblast globulin (ALG) are: A) the use of early bleedings after immunization to reduce the titer of antibodies which react with red blood cells and platelets; B) careful absorption with human red blood cell stroma and platelets; C) stabilization with non-crystalline silica dioxide; D) chromatography through QAE sephadex to remove pyrogens, microaggregates and possible inhibitors of ALG activity; E) careful safety testing in animals for toxicity and pyrogenicity; and F) testing in vitro for sterility. Such a purified horse ALG (IgGab) can be administered safely intravenously to patients to supplement a standardized immunosuppressive regimen incorporating azathioprine and prednisone. Under these circumstances, allergic reactions are very rare, antibodies to horse IgG do not develop, skin tests to horse IgG remain negative, and immune elimination of circulating horse IgG from the human circulation cannot be demonstrated. The overall results of ALG patient survival and transplant function after 184 consecutive first cadaver transplants at the University of Minnesota demonstrate a statistically significant improvement in both parameters accompanying increases in ALG dose while rigidly utilizing standardized doses of azathioprine and prednisone. There is a significant reduction in the number of grafts lost to rejection; significant reduction in the number of rejection episodes; significant delay in the onset of rejection episodes; but there is no increase in septic loss of patients or kidneys. These efforts could be seen in the gross data or when subgroups controlling for patient age, tissue typing were analyzed. Excluding patients at high risk did not alter the results. The beneficial effects of ALG were particularly striking in good matches. In the highest doses, ALG may be dangerous for older patients with poor matches who develop an increased incidence of septic loss of kidney and/or life. Thus, ALG appears to be a useful adjunct in the early management of cadaver transplants by reducing the incidence and frequency of rejection episodes. The dose should probably be reduced in the older patients who receive kidneys from badly mismatched donors. One cannot conclude from this study that ALG manufactured in other centers by this or other techniques, will accomplish the same results since the multiplicity of factors involved in the success and failure of transplants must be controlled so that the influence of intravening variables in the assessment of ALG effectiveness can be assessed.
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Passively acquired hemagglutinating antibodies may be detected in the serum of patients receiving horse anti-lymphoblast globulin (ALG) or anti-thymocyte globulin (ATG). Thirty-seven patients receiving ALG following renal transplantation were studied. Eight patients monitored daily all developed positive direct antiglobulin tests (DAT) and positive red cell antibody screening tests. Fifteen of 32 recipients developed red cell antibodies reactive at room temperature in saline, 4 of 32 in albumin at 37 degrees C, and 33 of 37 in the antiglobulin test. Horse globulin was detected on the red cells of all six recipients tested with rabbit anti-horse globulin. Ether eluates prepared from the red cells of 20 patients showed no specificity for common red cell antigens. Anti-human globulin (AHG), absorbed with ALG-coated red cells to remove the component in the AHG which was crossreacting with horse globulin, was used successfully for antibody screening and identification, direct antiglobulin testing, and/or the antiglobulin crossmatching of 27 ALG and ATG recipients, including five with red cell alloantibodies.
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