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Biomedical subjects

L J Perloff

Publications and source records attributed to L J Perloff.

At least 55 records · Page 3Linked to original sources

Studies of the immediately vascularized skin allograft.

In order to evaluate the effect of the nature of revascularization on survival rates of skin allografts, a rat model was devised which provided simultaneous and immediate establishment of arterial and venous blood supply to a composite skin-renal allograft. For 5 days after transplantation the skin portion of the composite grafts appeared normal, with minimal inflammation in 11 recipients. From 6 to 11 days, in 6 rats, active rejection developed with a marked inflammatory reaction of the skin-kidney interface. In 10 rats in which the composite grafts remained in the secondary hosts for 12--21 days rejection of the skin was complete. The renal portion of all composite grafts appeared normal in all three panels and all recipients of composite grafts rejected subsequent orthotopic skin grafts in an accelerated manner, with median survival time of 8.2 +/- 0.3 days compared with 11.5 +/- 0.7 days in untreated Fisher leads to Lewis controls. These results demonstrate that the skin on the composite graft retained its immunogenicity, that immediately vascularized skin allografts between AgB compatible rats will be rejected in a normal time and that anatomical factors are not sufficient to account for the difference in survival times between skin and solid organs.

Animals↗

Inadvertent transplantation of a melanoma.

A cadaver renal allograft recipient with normal function for over 3 years developed metastatic melanoma and died within months despite cessation of immunosuppression and allograft nephrectomy. Two additional immunotherapeutic modalities were attempted when it became obvious that the tumor was not a de novo malignancy but rather an inadvertently transplanted one. Neither reexposure to the allograft antigens nor administration of alloantiserum from the patient who had received and rejected the mate of the kidney from the same donor affected the rapid growth of the melanoma in our patient. Of extreme interest is that a focus of melanoma was found in the allograft removed from the surviving patient.

Adult↗

Relapse of pneumonia caused by cytomegalovirus in two recipients of renal transplants.

Two cases of relapse of pneumonia caused by cytomegalovirus (CMV) in recipients of renal transplants were studied. Between episodes of pneumonia, both patients recovered completely as judged by X-ray clearing and by resolution of fever and respiratory symptoms. CMV was isolated during each episode of pneumonia from lung tissue, pleural fluid, or buffy coat cultures. Serologic studies revealed a rise in titer of antibody, confirming recent infection with CMV during the first epidose of pneumonia in each patient. Intranuclear inclusions consistent with CMV infection were detected in each of the three episodes where lung tissue was obtained. Special stains and cultures for Pneumocystis carinii, fungi, Nocardia, and mycobacteria yielded negative results. The renal allograft continued to function in both patients after they recovered from the first bout of pneumonia, and the relapse was temporally related to reinstitution of aggressive immunosuppressive therapy. The relapse of pneumonia emphasizes the need for caution when immunosuppressive therapy is reinstituted after recovery from serious CMV infection.

Adolescent↗

Lethal post-transplantation calcinosis.

The case studies of four patients with post-transplantation calcinosis are presented. Three of the four patients died of inanition and sepsis secondary to infection of extensive soft tissue ulcers and diffuse cutaneous vascular calcification with gangrene. The fourth patient survived following removal of all four parathyroid glands and autografting of approximately one-half of one gland. Common to the patients was secondary hyperparathyroidism, elevated mean serum calcium levels after transplantation, and radiographic evidence of small and medium vessel calcification. No other differences could be found between these patients and other patients with post-transplantation hyperparathyroidism without calcinosis. In the face of apparently minor complaints of lower extremity discomfort, elevated parathyroid hormone levels (PTH) and positive xerography may indicate subtotal parathyroidectomy regardless of the serum calcium level.

Adult↗

The immediately vascularized skin allograft.

A model for immediate vascularization of skin was devised to examine one of the possible explanations for the differential survival rates of transplants of freely grafted skin and organs, i.e., the increased vulnerability of skin to early ischemic necrosis prior to revascularization. Female Fischer (F) rat skin was transplanted beneath the kidney capsule of tolerant female Lewis (LEW) recipients. This skin healed in and initially appeared to be normal grossly and microscopically. In 27 rats, after 30 days, the composite grafts were excised, and immediately transplanted by means of vascular anastomosis into normal LEW recipients (syngeneic to the kidney portion of the graft and allogeneic to the skin). For 5 days after transplantation of the composite graft, the skin appeared to be normal with minimal or no inflammation in a panel of 11 recipients. From the 6th to 11th day, an active rejection reaction developed at the skin-kidney interface in a panel of six rats. In 10 rats, in which the composite grafts remained in their secondary hosts for 12 to 21 days, rejection of the skin was complete. The renal portion of all composite grafts appeared to be normal histologically. All recipients of composite grafts rejected subsequent orthotopic F skin grafts in an accelerated manner, with median survival times of 8.2 +/- 0.3 days compared to 11.5 +/- 0.7 days in untreated F leads to LEW controls, demonstrating that the skin on the composite graft was fully immunogenic. These results demonstrate that immediately vascularized skin allografts between rats compatible at the major Ag-B1 locus will still be rejected within 2 weeks compared to survivals of up to 48 weeks in renal allografts in the same histocompatibility combinations, suggesting that anatomical factors are not sufficient to account for the differences in survival times between skin and solid organs.

Animals↗

Live cytomegalovirus vaccination of renal transplant candidates. A preliminary trial.

Significant morbidity and mortality are associated with primary cytomegalovirus infections in renal-transplant recipients. In the hope that immunity to cytomegalovirus could safely be established before transplantation, we vaccinated 12 seronegative renal-transplant candidates with the Towne 125 strain of live human cytomegalovirus. Before transplantation, there were no significant reactions except for erythema and induration at the site of inoculation. All vaccinees seroconverted, and the three patients tested acquired a cytomegalovirus-specific cellular immune response. Ten vaccinees underwent transplantation: Nine have completed at least 3 months of follow-up, and eight retain functioning allografts up to 1 year later. Although cytomegalovirus was isolated from six patients after transplantation, the restriction endonuclease patterns of the viral DNA of four of these isolates differed significantly from those of the vaccine strain. Therefore, it appears that the vaccine strain did not become latent in the host, at least in a form that could be reactivated.

Cytomegalovirus↗

Influence of histocompatibility and transplant site on survival.

Suggestions that endocrine tissue is privileged, in that it may not be as severely damaged by the allograft reaction, provided the stimulus for an evaluation of thyroid transplantation across various histocompatibility barriers and into a number of different recipient sites. Results of allografting reveal that Ag-B compatibility allows for prolonged survival of thyroid tissue (much longer than skin in the same histocompatibility combinations) in the following sites: intramuscular, intradermal, renal subcapsular, and anterior chamber. Only the intrasplenic site, however, did not allow survival of even weakly incompatible grafts. In addition, all recipients of thyroid allografts rejected subsequent donor strain skin grafts in an accelerated manner, attesting to the normal antigenicity of thyroid. This finding, that thyroid is a "relatively privileged" tissue, has not been reported previously and is encouraging, since it suggests the potential success of clinical transplantation of other endocrine tissue less easily replaced than thyroid by administration of naturally occurring of synthetic analogues. Further, mild immunosuppression may serve to prolong survivals of allografts of endocrine tissue such as parathyroid or pancreatic islets, especially if an immunologically privileged site is employed.

Animals↗

Studies of the modified venous allograft.

Segments of rat inferior vena cava were modified by proteolytic digestion and dialdehyde starch tanning in an attempt to alter their antigenic nature and increase their tensile strength. These tissues were found to retain their ability to sensitize allogeneic recipients in both the intradermal and intra-aortic positions in all 50 experimental animals. Furthermore, these grafts had a very high aneurysm formation (100%), and aneurysm rupture (54%) rate even in isogeneic recipients, suggesting that the modification procedure so damages the structural integrity of venous tissue that its use in clinical situations may have disastrous consequences. Histologic evidence of intimal thickening, elastic disruption, and often severe acute and chronic inflammation supported the gross evidence of mechanical and immunologic damage and suggests that a mild brief course of immunosuppression may be indicated in clinical trials in situation in which autogenous saphenous vein in unavailable. Although the use of prosthetic mesh support for the graft may help to avoid structural changes, the introduction of synthetic materials may offset the theoretical advantages of the venous tissue.

Aldehydes↗

Successful renal vein reconstruction with bovine arterial heterografts.

Extensive damage to a short right renal vein complicated transplant surgery in two patients. The use of a segment of modified bovine arterial heterograft permitted successful transplantation in both cases. These results are in contrast to the reported inability of bovine arterial heterografts to remain patent elsewhere in the systemic venous system.

Adult↗