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Survival statistics of 163 cadaver and 60 live related donor renal transplants from a single center were analyzed. Survival rates at one, two and three years for 38 first cadaver transplants matched for a haplotype and 34 first live related donor haplotype matched kidneys were virtually the same. In addition, nine, four antigen matched cadaver transplants had a comparable survival rate at one, two and three years to the larger group of 25 HL-A identical live related donor kidneys. When poor risk cadaver recipients were excluded from the entire cadaver group, the graft survival rate approached that of the live related group at one year but declined more rapidly at two and three years than did the live related donor group. Thus, cadaver renal transplantation in this series appears to be an alternative to comparably matched live related donor transplants. An increased effort should be made to identify and use brain death cadaver donors for transplantation. As more donors become available and national sharing systems are improved, a strong case can be made to avoid the use of live related donor kidneys, except in instances of a perfect match.
The cadaver in the Han Tomb No. 1 at Mawangtui near Changsha, Human Province, excavated during the Great Proletarian Cultural Revolution and the movement to criticize Lin Piao and Confucius, is the remains of the wife of Litsang, the Marquis of Tai, the Chancellor of the principality of Changsha in the early Western Han Dynasty. The cadaver, buried underground for more than 2,100 years, is very well-preserved. The results presented in this paper are a part of the multidisciplinary investigations of the state of preservation of the cadaver, which, together with the studies of the pathological changes and the cause of death, and the attempts at unveiling the secret of preservation, constituted the main objectives of the coordinated research activities for the Han cadaver. This paper describes the fine structure of the muscle and other tissues of the cadaver. By an extensive analysis of the electron micrographs of the psoas muscle, by fractionation of various fragments of the same, and by simulation experiments with fresh human muscle incubated with cathepsins, it is possible to show that the muscle fibril assumes the shape of a bamboo shoot and is made up of a stack of alternate layers of two "half A disks" (one wing of the A cylinder minus the H zone) to one Z disk, held together by remnants of the microfilaments and wrapped up in the sarcoplasmic reticulum. The H zone of the A band and the I filaments have preferentially autolyzed. The best preserved portions of the Han muscle still retain antigenicity to a certain extent. The best-preserved of all proteins is collagen, retaining much of the macromolecular, chemical and biochemical characteristics, whereas pancreatic enzymes, cytochrome C and other stable proteins could no longer be detected. The separation of degradative processes into endogenous autolysis and exogenous putrefaction, the synthesis of the factor of macromolecular stability and the factor of autolytic environment, and the disentanglement of the changes occurring soon after death and the long-term gradual changes, have been discussed in an attempt to understand how the corpse changed in the course of time and why it was so well-preserved. The well-preservedness of the cadaver of the Marquise of Tai once again testifies to the creative wisdom of the labouring class of our ancestors.
The long-term function of 110 cadaver kidney transplants preserved by hypothermic perfusion was compared with that of 79 fresh cadaver kidneys. The one-month failure rate was 4 percent in the perfused kidneys in contrast to a 32 percent one-month failure rate reported by one cooperative group. These data were again confirmed in a prospective, paired study comparing perfused and fresh cadaver kidneys from the same donor. Thus, perfusion of kidneys was not harmful for cadaver transplantation. In fact, of 83 first cadaver transplants, less than 30 percent of perfused kidneys failed in the first year. There appears to be no evidence supporting the idea that bloodless hypothermic perfusion permanently damages human kidneys or increases the chances of rejection.
Excellent cadaver allograft survival has been achieved with kidneys from cadaver donors pretreated with high intravenously given dosages of cyclophosphamide and intravenous injections of methylprednisolone. To test the efficacy of this method of pretreating the donor, allograft survival in 21 patients, group A, receiving kidneys from cadaver donors pretreated with 4 grams of cyclophosphamide and 4 to 6 grams of methylprednisolone given intravenously was compared with two other groups of cadaver allograft recipients, 39 patients, 23 group B patients receiving untreated kidneys harvested at the Mayo Clinic and 16 group C patients receiving untreated kidneys harvested elsewhere. Two year actuarial allograft survivors were 16 of 21 in group A, 13 of 23 in group B and seven of 16 in group C. We believe that cadaver donor pretreatment improves allograft survival significantly.
The effect of HLA matching on the success of cadaver renal allografts was examined utilizing computerized multifactoral analysis in a large single renal transplant center. One hundred ninety-one consecutive cadaver transplant recipients (from January 1968 to August 1975) were followed from 2 1/2 to 9 years. During the period surveyed we had not utilized the tissue typing results in a prospective manner to select recipients. The data presented attest to the beneficial effect of utilizing well matched cadaver grafts. HLA matching of two or more antigens results in significantly superior 2- and 4-year patient survival and graft function compared to results for cadaver kidneys matched for zero and one HLA antigen. The results are not greatly influenced when age, sex, or time of transplant are controlled. The importance of tissue typing is particularly clear if higher doses of antilymphoblast globulin (ALG) are administered. The risk inherent in advancing recipient age is markedly reduced by better transplant matches. Graft function is also superior in the diabetic patients receiving good HLA matches, but there are too few patients to make these results statistically significant.
The effect of blood transfusion was analyzed in 194 first cadaver renal transplants and 86 living related renal transplants. The association of blood transfusion with HLA genotyping and poor risk recipients was analyzed. Exclusion of poor risk recipients improved graft survival among the transfused group of patients but not in the small subgroup of nontransfused recipients. No effect of blood transfusion was observed in the living related group. Improved graft survival was observed in both the haplotype-matched and nonhaplotype-matched transfused cadaver recipients. The haplotype-transfused recipients had grafts survival rates of 69 and 66% at 1 and 2 years, respectively. The greatest beneficial effect was seen in the double haplotype-transfused cadaver recipients with graft survival rates of 80 and 71% for the same period. The lack of beneficial effect of transfusion in the living related patients is felt to be a result of the fact that the maximum effect had already been achieved by a far superior donor-recipient histocompatibility than is able to be achieved in a large group of cadaver recipients.
Between August 1967 and January 1977, 699 cadaver kidneys were preserved and transplanted in our hospital after continuous perfusion with cryoprecipitated plasma. Overall graft survival of primary transplants was 55 +/- 2 per cent at one year and 41 +/- 2 per cent at four years. The results with ninety-six second transplants were similar. The number of HLA antigens shared and the duration of preservation did not influence graft survival. Patient survival among 426 cadaver graft recipients since September 1972, when lower dose immunosuppression was started, was 91 +/- 1 per cent at one year and 84 +/- 2 per cent at four years, significantly better than survival before then. Survival of fifty-two recipients of cadaver retransplants since September 1972 was 86 +/- 5 per cent at one year and 86 +/- 5 per cent at four years, which was better than before. The incidence of posttransplantation dialysis was 30 per cent and did not correlate with the length of preservation. Primary wound infections, primary ureteral extravasation, and vascular complications each occurred with an incidence of 1.1 per cent or less in patients treated with lower dose immunosuppression. Only four kidneys were lost because of complications, and in no instance was the need for transplant nephrectomy directly related to the method of preservation. Perfusion preservation with cryoprecipitated plasma gives excellent results compared with alternative methods.
Optimal preservation of renal and ureteral structure and function is attempted by maintenance of renal circulation during heart-beating cadaver nephrectomy. Modifications of Ackermann's en bloc procedure for removal of cadaver kidneys are suggested to adapt this procedure to the heart-beating cadaver situation.
This study, based on results of 252 cadaver kidney transplantations, shows that some factors which reflect individual immune response capacity, such as ability to produce anti-HLA antibodies, sex and response to hepatitis B virus, appear, along with HLA compatibility, to markedly influence renal graft survival and leads us to propose the following new guide-line for cadaver kidney recipient selection: For "good responders" (i.e., patients with anti-HLA antibodies, females and HBs Ag negative individuals) a close HLA compatibility with the donor (3 or 4 antigens in common) is necessary, while this need not be observed for "non-responders" (i.e., patients without preformed anti-HLA antibodies, males and HBs Ag persistent carriers). Furthermore, review of recent methods proposed for detecting early cellular and humoral manifestations of rejection leads to proposal of the following immunological monitoring of the transplant recipient. Systematic and frequent testing for circulating cytotoxic cells and antibodies against donor antigens, regular dosage of complement factors and of the nephretic factor, and investigations for the migration leukocyte inhibiting factor and macrophage arming factor, possibly produced in vitro by lymphocytes. Both these protocols for recipient selection and immunological monitoring can henceforth be applied and may contribute to improve cadaver kidney transplantation prognosis.
A one year pilot project conducted at a 2,000 bed medical center involved a unique approach to the retrieval from cadavers of multiple viable organs and tissues. Aspects of the program included a special unit for sterile evaluation and storage of tissue, a computerized registry of potential donors, a nurse to coordinate and expedite retrieval, and a retrospective chart review to define the incidence and location of potential cadaver donors. There were requests for 121 tissues by 39 investigators. Eleven different tissues were needed within 4 hours of death. Forty-two percent of individuals contacted directly enlisted in the donor registry, three of whom were identified on the computer at the time of death. A five-fold increase in cadaver donor evaluation referrals occurred, and one third of referrals resulted in viable tissue retrieval. A review of 728 deaths indicated that 45% could have been potential eye donors, 27% pancreas donors and 2.5% kidney donors. A coordinated program to retrieve multiple viable organs and tissues for transplantation and research appeared to be effective in this initial pilot study.
One hundred fifteen consecutive patients received first transplants from cadaver donors at the University of Minnesota between January 1, 1968, and May 31, 1973. All patients have been followed for at least two years. The two-year survival rate is 70 per cent and the two-year transplant function rate is 58 per cent. Considerable improvement in both patient survival and transplant function has been noted since 1971. The success of transplantation appears to depend to a large degree on the age of the transplant recipient, the number of HLA antigens matched between donor and recipient, and the dose of antilymphoblast globulin (ALG) administered to the recipient during the first two weeks after transplantation. Each of these factors appears to be important even when the other factors are controlled, and when patients with diabetes, suffering technical failure or hyperacute rejection, are excluded. The results utilizing well-matched cadaver kidneys plus large doses of ALG appear to be equivalent to those obtained with the use of mismatched kidneys from relatives, but further analysis will be required to draw a definite conclusion. Patients receiving poorly-matched cadaver kidneys do far less well than patients receiving mismatched related grafts, however, even when ALG is utilized.
1. A rapid and sensitive semi-micro method for the determination of hippuric acid formation by tissue samples in vitro is described and applied to the determination of the post-mortem survival of hippuric acid formation in rat and human cadaver tissue samples. 2. Hippuric acid formation survived in rat and human cadaver liver for at least 72 h when corpses were stored at 4 degrees. 3. Hippuric acid formation was detected in human cadaver liver and kidney samples and was absent from brain, intestine, heart and lung. 4. Post-mortem liver samples from a case of acute pancreatitis failed to form hippuric acid as did kidney samples from a case of systemic lupus erythematosus with renal involvement.
The authors have investigated 17 kinds of findings of 34 cadavers in the water and 17 newborn-infant cadavers in liquid feces-urine mixture in privies which had remained at known postmortem interval and had been subjected to medico-legal autopsies in our laboratory. The conclusions are as follows: The progress of the cadaveric phenomena in the water and liquid feces-urine mixture is slower than in the air. The time ratio of the progress of the phenomena in the media to those in the air is not the same for all kinds of the findings, and hence it is not possible to apply the criterion of the estimation of the postmortem interval for the cadavers in the air to those in the water and liquid feces-urine mixture by any correction.
Perfusion of cadaver kidneys up to 48 hours did not adversely affect the long-term renal allotransplant function and did not result in an increased rate of rejection. In fact, cadaver kidneys perfused for longer periods of time had a slightly better functional survival rate than did kidneys perfused for shorter periods. From 100 perfused cadaver kidneys, we can conclude that the length of perfusion had little if any effect on the immunogenicity of the renal allograft in the immunosuppressed transplant patient.
The effects of cadaver storage on endothelial survival are assessed by the temperature reversal effect in rabbit eyes. Eyes removed at death show little deterioration after one week of refrigerator storage. Eyes left in the cadaver from one to four hours after death show increasing deterioration with time in the body; the deterioration becomes more pronounced as the days of refrigerator storage increase. The sooner an eye is removed from the body, the more reliably it will survive refrigerator storage.
To determine the prevalence of potential cadaver kidney, eye, and research-tissue donors in a tertiary referral hospital, the charts of 718 patients who died were studied. We found a potential kidney-donor rate of 2.4 per 100 hospital deaths, a potential eye-donor rate of 45.4 per 100 deaths, and a potential pancreas-donor rate of 26.5 per 100 deaths. In the study year, 20 potential cadaver kidney donors were projected, theoretically meeting the needs of the transplantation center. Recognized potential eye and pancreas donors were remarkably numerous. Effective education, surveillance, and procurement programs are necessary to salvage these potential donor tissues.
1. The generally poor state of soft tissue preservation that complicates observations by gross dissection and light microscopy posed no hindrance to scanning electron microscopic (SEM) studies of bone surface, because all of the soft tissues are chemically removed. 2. Specific and identifiable surface patterns representing locations of periosteal and fibrous muscle attachments can be readily observed in cadaver tissue with the SEM. 3. SEM observations confirmed earlier literature concerning the extent of periosteal and intraosseus attachments of the masseter muscle. The masseter muscle attached periosteally on the lateral surface of the mandible and along the inferior border. Just above the inferior border, a ridge of intraosseous attachment was noted. 4. The correlation of SEM observation of bone surface patterns with gross dissection and light microscopy demonstrated that SEM can be useful in determining the extent of muscle attachments in cadaver tissue even when the soft tissue is poorly preserved.