Demonstration of donor-specific T suppressor lymphocytes in rats accepting orthotopic liver allografts.
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Biomedical subjects
Publications and source records attributed to R Engemann.
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Transplantation of the intrathoracic inferior vena cava into the abdominal inferior vena cava of the recipient was performed in inbred rat strains of the following combinations: Syngeneic F344 leads to F344, RT-1-identical allogeneic LEW leads to F344, and RT-1-different allogeneic CAP leads to F344. In the RT-1-different combination subgroups with presensitization (blood, skin) were formed. The transplanted veins were evaluated at different times, macro- and microscopically. To test humoral immunology reactivity, we used a modified hemagglutination test, to analyse cell-mediated reactivity, subsequent skin grafts. The following results were obtained: 1) Aside from sporadic mononuclear cells caused by the operation technique, syngeneic vein grafts do not show any macroscopically visible and microscopically detectable changes. 2) Weakly allogeneic vein grafts do not lead to microscopically detectable changes in the graft. Strongly allogeneic vein grafts cause temporary mononuclear cell infiltration, which subsides within 21 days, without influencing the morphologic structure of the vessel wall. 3) In the RT-1-identical allogeneic strain combination, only accelerated skin graft rejection time indicates systemic sensitization, in the strongly allogeneic system, the increase of hemagglutinating antibodies also does this. 4) In both the RT-1-identical allogeneic strain combination and the RT-1-different allogeneic one, a proven sensitization does not lead to a permanent morphologic alteration. 5) Only presensitization with strong antigens (skin) leads to a macroscopically visible, as well as microscopically detectable, rejection reaction.
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Liver transplantation is gradually beginning to move from the experimental to the clinical stage. Of the approx. 340 human "transplantation" which have been carried out worldwide, approx. 250 were performed by the transplantation teams in Denver and Cambridge. They were performed orthotopically. The detailed analysis of the indications by Calne ( n = 81) and Starzl (n = 153) is supplemented by analysis of the course of a total of 223 cases. Individual cases, such as a child with a liver transplant which is functioning for 9 1/2 years, show that liver transplantation is possible. Statistically, however, liver transplantation still involves a big question mark. Nevertheless, the Denver team has announced a 1 year survival quota of almost 50%. In the statistics on the causes of death, technical complications are clearly on the decline. The biliodigestive anastomosis constituted a "locus minoris resistentae", recently, however, the complication rate has been lowered considerably by the use of a Roux-Y-loop bypass and an intermediate gallbladder conduit. Infectious complications - bacterial, fungal and viral - caused or at least promoted by immunosuppression are a main problem. The special immunologic situation of the liver in transplantation has as yet not been clarified either experimentally or clinically. Unequivocal evidence of graft rejection is often difficult, because infectious and drug-induced liver intoxications can produce similar symptoms.
(1) Arterial transplants used as arterial replacements induce sensitization of the recipient in the weakly as well as in the strongly allogeneic systems (afferent limb). (2) Venous transplants used as venous replacements induce sensitization of the recipient (afferent limb). (3) Arterial transplants show increasingly severe rejection reactions paralleling the degree of immunogenetic difference (efferent limb). (4) Veins transplanted as venous replacements are tolerated even in the strongly allogeneic systems (efferent limb).
Experimental microsurgical techniques using a magnifying glass and surgical microscope enable nearly all abdominal operations and organ transplantations to be performed in rats. Vascular and prosthetic segment implantations, portocaval anastomoses, heterotopic heart-, kidney-, spleen-, pancreas-, and liver transplantations some with superselective organangiography, are excellently demonstrated. Continuing research in microsurgery has considerably expanded experimental surgery and given new impulse to clinical surgery.
Systemic sensitization is induced by arterial transplants in the high pressure system and by venous transplants in the low pressure system. In aorta transplantation the severity of the rejection corresponds directly to the immunogenetic differences between donor and recipient; the efferent limb is triggered into action. For application of allogeneic veno-venous transplants this is not the case: despite systemic sensitization, even strongly allogeneic venous transplants are maintained over long periods. A threshold value is not reached unless there is presensitization with strong antigens, after which morphologically comprehensible rejection reactions, i.e. round cell infiltration, are demonstrated even in veno-venous transplants.
Controversial results have been reported regarding the importance of the duodenal food passage after total gastrectomy. There are a number of experimental and clinical studies showing an advantage for the jejunal interposition between esophagus and duodenum. Others favor the Roux-en-Y reconstruction, as it is technically less demanding. The purpose of this study was the randomized comparison between two major reconstruction principles after total gastrectomy for gastric cancer (i.e., jejunal interposition with pouch versus Roux-en-Y pouch reconstruction). A group of 120 patients with gastric cancer were randomized and operated on during a 5-year period according to standardized operative protocols, using either a jejunal interposition with pouch (JIP) or the Roux-en-Y reconstruction with pouch (RYP). Endpoints of this study were operation time, intra- and postoperative problems and complications, patients' body weight, functional assessment, and quality of life. Of the 120 patients, 14 had to be withdrawn during the operation because only the Roux-en-Y reconstruction was technically possible. Finally, 53 patients with JIP were compared with 53 patients with RYP for the perioperative course. There were no significant differences between the two procedures (RYP and JIP) regarding complications (24.5% and 26.4%, respectively), mortality (3.8% and 1.9%, respectively), and operation time (4.35 hours and 4.40 hours, respectively). For long-term functional comparison 46 (RYP, n = 26; JIP, n = 20) patients were without recurrence after 3 years of survival. Comparison of body weight, Visick scoring, and the Spitzer Index also did not reveal any significant difference between the two operation methods.(ABSTRACT TRUNCATED AT 250 WORDS)