Whole-organ Transplantation Research Articles

Pancreas transplantation with pancreatico-duodeno-cystostomy for exocrine drainage: cystographic findings.

Pancreatic transplantation is becoming accepted therapy for a select subset of patients with type 1 insulin-dependent diabetes. At many centers, whole-organ transplants with pancreatico-duodeno-cystostomy for drainage of exocrine secretions is the preferred surgical procedure. We obtained 21 cystograms in nine patients who underwent this procedure who were suspected of having anastomotic leaks and possible abscess. Positive findings included extrinsic bladder compression (nine patients), filling of the transplanted duodenal segment (three patients), edematous bladder wall (four patients), intraperitoneal (two patients) and extraperitoneal (four patients) leaks, and fistulae (two patients). Intraperitoneal extravasation resulted in abscess formation and cutaneous fistulae, and these transplants were subsequently removed. We conclude that cystography is a useful technique in evaluating the site and extent of anastomotic leaks and fistulae.

Long-term endocrine function of duct-ligated pancreas isotransplants in rats.

Duct-ligated pancreas transplants were used to study the long-term B cell function after total acinar atrophy. Vascularized whole-organ pancreas transplantation was performed in 47 streptozotocin-diabetic inbred Wistar rats. Of 31 recipients which survived the first week, 30 were permanently cured of the diabetic state with restoration of normal blood glucose levels within 24 h. Metabolic and morphologic studies were performed for up to 16 months after transplantation, i.e. for most of the normal life span of the rats. The recipients of duct-ligated, heterotopic transplants demonstrated plasma insulin (IRI) values slightly above normal. Median blood glucose values were significantly lower than in the normal controls. Basal and stimulated IRI as well as glucose tolerance tests failed to reveal any reduction in the endocrine capacity of the transplants as compared to nondiabetic control. Light-microscopic examinations of grafts showed total acinar atrophy after the first weeks of duct occlusion. No apparent reduction of islet tissue was noted. The results demonstrate that total occlusion of the exocrine ductal system does not impair B cell function of the rat pancreas. The duct-ligated pancreatic transplant permanently reverses induced diabetes when pancreatitis and immunologic reactions are avoided.

CYCLOPHOSPHAMIDE AND HUMAN ORGAN TRANSPLANTATION

Cyclophosphamide, a drug that has not previously had an important role in whole-organ transplantation, was given as a primary immunosuppressant to one liver and eleven kidney recipients, in combination with prednisone and horse antilymphocyte globulin. One of the patients died despite good renal-graft function. Two kidneys from a common cadaveric donor failed. The other nine patients have excellent function of their homografts after 2-3 months. Cyclophosphamide was substituted for azathioprine in one hepatic and five renal recipients who were suspected of having liver toxicity from azathioprine 3 months to almost 8 years post-transplantation. Graft function was maintained after this change, and the evidence of liver injury subsided.

Experimental renal heterotransplantion. II. Closely related species.

SUMMARY The results of xenogeneic transplantation of tissues in closely related species were compared to those of allografts. A comparative study of transplantation of whole organs, skin grafts, and tritiated thymidine labeled cells into nonsensitized and sensitized recipients was made. Antibody responses were measured. Xenograft and allograft rejection was mediated by cellular mechanisms in nonsensitized recipients. The histologic pattern of rejection was identical. Nonsensitized recipients rejected xenografts slightly faster than allografts. In sensitized recipients, xenografts were rejected wholly by humoral mechanisms, but allografts were rejected both by cellular and by humoral mechanisms. The temporal pattern of rejection was the same in sensitized recipients of allografts or xenografts. In nonsensitized recipients, antibodies to erythrocytes developed more rapidly after xenografting than after allografting, but in sensitized recipients the titers were similar. Cytotoxic antibody was present in sensitized animals that received either xenografts or allografts but the titer was higher in the xenograft recipients. These observations suggest that humoral factors influence the temporal and histologic pattern of rejection. In closely related xenografts, humoral factors are the primary mediators of rejection only after sensitization. However, in sensitized allograft recipients, cellular and probably humoral mechanisms participate.

Heart preservation utilizing hyperbaric oxygen and hypothermia

HE F E A S I B I L I T Y OF WHOLE ORGAN Ttransplanta t ion has awakened an interest in certain areas of investigation and crystalized attention to the magnitude of certain problems. Early transplantation work involved cells and small portions of tissues; however, the problems now have advanced to the stage of transplantation of whole organs. The problem areas are rather well defined: the surgical technique of whole organ transplantation, immune or rejection response and the organ availability or organ preservation. Of t h w problems, two are now receiving paramount attention and one is solved. The technical problems of whole organ tramplantation have been studied and overcome, and the s u c d u l surgical exercises are now a reality in many centers. The immune-rejection response is a formidable problem and is now under investigation but will require extensive research into cell metabolism and the transference of the immune mechanism. The yielding of the surgical technical problems to experimental solution has brought forth the paramount problem of having an organ suitable for implantation when needed. Since it is imposible to produce the organ for implantation, the organ must be obtained from another human subject at a given time when the subject has succumbed to either accidental death or disease, and the organ must be obtained in a viable oxygenated stage and pmSCrved until the recipient is prepared for implantation. This vital need s thus stimulating the search for means of maintaining the whole organ viable for a period of one or more days until the redpient can be hmpitalized, evaluated and

Homologous lung transplantation (experiences in the dog)

The feasibility of whole-organ transplants has received a great deal of impetus by the successful homotransplantation of the kidney in the human. 1 Ever since Carrell 2 described in 1908 the technical feasibility and biological aspects of such transplants, many investigators have tried to produce successful transplants. The replacement of a whole lung would be beneficial in many disease entities. The first attempt of lung transplantation using pulmonary lobes was made by Standacher and associates. 3 In 1951, Juvenelle et al. 4 reported the successful autologous transplantation of the right rung in the dog. After this, Neptune et al. 5 Hardin et al. 6 and Davis et al. 7 independently reported successful homotransplantation of the left lung in the dog. Hardin and Kittle 9 reported 2 survivals following left lung homotransplantation in the dog with contralateral pneumonectomy. The actual function of the homotransplant was not discussed by any of these

The homograft response to whole-organ transplantation of the canine spleen

Summary o 1. A one-stage technique of canine spleen transplantation has been developed which leaves the transplanted spleen in normal anatomic position with the splenic vessels united by end to end anastomosis. 2. Using this technique, 43 homotransplantations and 12 autotransplantations of the spleen have been carried out. Many operations failed to achieve prolonged vascularization of the spleen owing to suture line thrombosis; but 22 homografts and 6 autografts showed excellent vascularization at reexploration. Subsequent histologic changes were followed by periodic biopsies of the spleen. 3. Homotransplanted spleens usually show destruction of the splenic architecture with widespread necrosis by the end of one week. There is a transient early phase of striking follicular activity in the homotransplanted spleen which may represent an immune response of the graft against its new host. This is quickly obliterated by a far greater reaction of the host against the graft. Histologically, the reaction directed against the graft is quite analogous to renal homograft rejection. 4. Autotransplanted spleens show essentially normal follicular activity and survive indefinitely

Homologous lung transplantation. Experiences in the dog.

The feasibility of whole-organ transplants has received a great deal of impetus by the successful homotransplantation of the kidney in the human. 1 Ever since Carrell 2 described in 1908 the technical feasibility and biological aspects of such transplants, many investigators have tried to produce successful transplants. The replacement of a whole lung would be beneficial in many disease entities. The first attempt of lung transplantation using pulmonary lobes was made by Standacher and associates. 3 In 1951, Juvenelle et al. 4 reported the successful autologous transplantation of the right rung in the dog. After this, Neptune et al. 5 Hardin et al. 6 and Davis et al. 7 independently reported successful homotransplantation of the left lung in the dog. Hardin and Kittle 9 reported 2 survivals following left lung homotransplantation in the dog with contralateral pneumonectomy. The actual function of the homotransplant was not discussed by any of these

Experimental whole-organ transplantation of the liver and of the spleen

Moore, F. D.; Wheeler, H. B.; Demissianos, H. V.; Smith, L. L.; Balankura, O.; Abel, K.; Greenberg, J. B.; Dammin, G. J.

Organ and Bone Marrow Transplants.

s1 May 1961Organ and Bone Marrow Transplants.J. W. Ferrebee, M.D.J. W. Ferrebee, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-54-5-1051_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTransplants of bone marrow have been found to restore hematopoiesis in animals rendered aplastic by lethal exposure to radiation. Animals so restored have been found to accept transplants of other tissue from their marrow donors. Efforts to expand this information to the point of clinical usefulness in either the treatment of radiation casualty or the transplantation of whole organs have revealed certain problems. Clearly immunologic tolerance can be acquired. The difficulty has been to make the methods of its acquisition clinically acceptable. Investigation has revealed several methods of promise: the use of fetal rather than adult hematopoietic tissue to restore... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Cooperstown, N. Y. (ML) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1961Volume 54, Issue 5Page: 1051-1052KeywordsBone marrowHematopoiesisTransplantation Issue Published: 1 May 1961 PDF downloadLoading ...

The postmortem survival of tissues: The effect of time and temperature on the survival of liver as measured by glucose oxidation rate

Summary 1. The measure of glucose oxidation rate by radio-carbon dioxide production from glucose C-14 in a standard incubation system has been employed as a method of studying the viability of liver tissues after death of the host, under varying conditions of time and temperature preservation, and by hepatic function following transplantation. 2. The rate of oxidation of glucose to CO2 is a measure of liver functional capacity that, when normal, demonstrates an entirely intact liver associated with normal histology, normal liver architecture and normal glycogen content. Levels of glucose oxidation rate that are significantly below normal are compatible with intact whole liver function after transplantation. 3. The ideal of maintenance of normal glucose oxidation rate upon incubation provides an objective toward which tissue preservation methods may be directed. 4. The use of hypothermia is effective in maintaining intact this measure of liver function. 5. Spontaneous cadaver cooling or cadaver cooling in still air in a deep freeze is unsatisfactorily slow. 6. Cooling by peritoneal lavage with or without short periods of hepatic cold perfusion is satisfactory in maintaining an intact organ histologically and an intact glucose oxidation rate. Short periods of postmortem normothermia even as transient as 30 minutes act significantly to the detriment of the tissue preservation. 7. Rapid and immediate postmortem perfusion cooling would be the clinical ideal; using this technique, in experiments of this type, we do not yet know the time limit of acceptable preservation. 8. Livers that exhibit glucose oxidation rates significantly below normal will, after whole-organ transplantation, demonstrate survival, maintain the life of the animal, and resume clinically intact liver function.

Experimental Whole-Organ Transplantation of the Liver and of the Spleen°

Moore, Francis D. M.D.; Wheeler, Brownell H. M.D.°°; Demissianos, Harry V. M.D.°°°; Smith, Louis L. M.D.†; Balankura, Okas M.D.††; Abel, Keith M.B., B.Ch.†††; Greenberg, Jonathan B. M.D.; Dammin, Gustav J. M.D. Author Information

Radiation and Borrowed Tissues

The first four papers in this issue of Radiology, originally presented as a Symposium on Bone Marrow Transplants and General Immunological Problems, at the Forty-fifth Annual Meeting of the Radiological Society of North America, in November 1959, discuss exciting new lines of thought in radiology. They deal with the transplantation of bone marrow and other tissues into individuals who have received lethal or near-lethal doses of radiation. The potential for the saving of human lives from radiation accidents is enough to stimulate us. Beyond this, however, are the implications of therapeutic application associated with radiation given purposefully to near-lethal dosages. This might be expressed as the concept of intentional approach to the brink of radiation disaster followed by heroic rescue through another's tissues. Spectacular medical advances may be achieved by this means. I t is possible that a cure for leukemia may be offered by such high-dosage whole-body irradiation, with cell repopulation from a donor's healthy marrow. The treatment of testicular tumors and other malignant neoplasms might be notably improved. A means may be offered for safe transplantation of whole organs from one human being to another. These hopes are not likely to be achieved easily. The combined efforts of the radiobiologist, geneticist, and immunologist have already paved the way. The reports given here are encouraging, but they also bear witness to the many problems that are yet to be surmounted. We do not know how high the levels of radiation dosage can be pushed, nor what is required for the suppression of such human disease as leukemia. Much remains to be explored in the immunological phenomena of acceptance or rejection between host and transplant. The late unfavorable sequelae are still an unsolved problem. But these difficulties should not cloud the remarkable achievements already attained. To have successfully effected the removal of a kidney into a new host and to have observed it functioning there—a living chimaera—gives high promise for a new era in medicine. What should be the radiologist's role in these new developments? Clearly, this is not a suitable activity for the casual amateur, but rather for highly integrated units of specialists. We can all be interested in the challenge of this research endeavor and inform ourselves concerning its progress. In the near future, however, few of us are likely to be directly involved in this endeavor, and this is as it should be. A comprehensive mastery of special radiobiological background by the radiologist is required. This must be closely allied to a cooperative effort by radiobiologists, radiological physicists, and other pertinent medical and biological specialists. All of these must be fully informed of the current state of similar work elsewhere.

Experimental Whole-Organ Transplantation of the Liver and of the Spleen

Moore, Francis D. M.D.; Wheeler, Brownell H. M.D.°°; Demissianos, Harry V. M.D.°°°; Smith, Louis L. M.D.†; Balankura, Okas M.D.††; Abel, Keith M.B., B.Ch.†††; Greenberg, Jonathan B. M.D.; Dammin, Gustav J. M.D. Author Information

Transplantation of kidneys, experimentally and in human cases

CUTE renal failure has been treated successfully in a fair number of cases by use of the artificial kidney.' Still this method of treatment has not a very useful application in the treatment of chronic kidney disease. With the marked prevalence of chronic renal disease it was thought worth while to undertake studies on transplantation of kidneys, hoping that a method of survival might be provided for the sufferers from chronic kidney diseases. It was realized that a great amount of experimental work has been done in this field, which on the whole has yielded very little evidence of a hopeful nature that the principle could be applied to human beings. It was suggested by much of the work done that there is little likelihood of survival of transplanted tissue from one animal or one patient to another . An analogy from skin grafting where very complete and careful studies could be carried out regarding the survival and final disintegration of the graft within four to six weeks was taken as some proof of what would happen in transplanted organs. It was agreed that if sections, or slices of organs, or cells of organs were transplanted, the analogy might be fairly closely applied . However, in the authors' opinion the grafting of an intact organ might involve entirely different principles . Undoubtedly, when skin or other cellular tissue is applied from one animal or patient to a large denuded area of the recipient, the whole mass of tissue is exposed to the cellular reaction, tissue fluid reactions, probably immune reactions and so on that can develop from such contacts . To the authors, however, it seemed quite a different problem in relation to the transplantation of whole organs . In severe toxemias such as uremia, septicemia and the like, exsanguination transfusions, as carried out by many investigators and clinicians, has shown some evidence of benefit . ods were, therefore, investigated to discover by Philosophically, therefore, the question arises what means the cells could best be protected

BERLIN

<h3>Annual Session of the German Surgical Society</h3> TWENTY YEARS OF TRANSPLANTATION RESEARCH At the annual session of the German surgical society, held as usual in Berlin the middle of April, the main topic under discussion was Twenty Years of Transplantation Research. Professor Lexer of Freiburg stated that the field of transplantation has been greatly extended. However, homoplasty, operative replacement of lost parts or tissues by similar parts from individuals of the same species, has been frequently unsuccessful. Our endeavor must be to discover the conditions under which homoplastic transplantation can be successful. Bier's articles on regeneration, published a few years ago in the<i>Deutsche medizinische Wochenschrift</i>, emphasized that tissues, to be suitable for transplantation, must regenerate to remedy a gap or defect. The transplantation of whole organs has been disappointing. The regenerative processes may be merely the result of parenteral proteotherapy. Suggestion and resorption may simulate a successful outcome, but