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Biomedical subjects

C F Barker

Publications and source records attributed to C F Barker.

At least 199 records · Page 11Linked to original sources

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↗

Successful islet transplantation in spontaneous diabetes.

Optimism for islet transplantation is based on reversal of diabetes artificially induced in animals by pancreatectomy or beta cell toxins. In naturally occurring diabetes, implanted islets might be destroyed by the etiologic agent of the original disease; e.g., virus infection, genetic factors, or autoimmunity. Genetically determined diabetes in obese mice, in fact, is resistant to islet transplantation. Since these mice are hyperinsulinemic and not similar to human juvenile onset diabetes (JOD), more appropriate models were sought, "BB" rats spontaneously develop a syndrome remarkably similar to human JOD. We have studied 279 BB rats. In 31 rats the sudden onset of severe hyperglycemia was observed. Sinc BB rats proved to be AgB2 on serological typing, WF (AgB2) donors were selected. Six hundred Wistar-Furth isolated islets were transplanted intraportally in 10 BB diabetic rats immunosuppressed with antilymphocyte serum. All 10 recipients became normoglycemic, remaining so for 1 to 6 monts. An additional animal model studied was virus-induced diabetes in mice, since viral etiology of human diabetes seems likely. DBA mice receiving encephalomyocarditis virus became severely and persistently diabetic. Eight received syngeneic fetal pancreas to the renal subcapsule and became normoglycemic. Removal of the graft 30 days later demonstrated viable islets histologically and resulted in recurrent diabetes. That virally induced murine diabetes and one spontaneous syndrome in rats which is similar to human JOD responded to beta cell implantation argues that this treatment will be effective in man.

Animals↗

Femoropopliteal vein grafts for claudication. Analysis of 100 consecutive cases.

One hundred consecutive femoropopliteal venous grafts in 85 patients with claudication were followed for five years. At this time, three limbs had been amputated, approximately one quarter of the patients had expired, and 70% of the grafts in surviving patients remained patent. It is concluded that this operation does not appear to increase the risk of amputation and in fact, may lessen it. Moreover, it is associated with minimal risk and generally provides long term relief of claudication, thus enhancing the quality of life in most patients.

Adult↗

Results of 100 consecutive femoropopliteal vein grafts for limb salvage.

One hundred consecutive patients with femoropopliteal autogenous vein grafts for limb salvage were reviewed five years later. In this group 40% died and 30% of the limbs had been lost at the end of five years. Limb survival correlated best with adequacy of distal run-off, but not with the presence or absence of diabetes. Forty-seven per cent of the grafts were still patent among surviving patients, and when combined with the limbs that were viable despite failure of the original graft, 70% of the limbs were salvaged among the survivors at five years. Temporary graft patency was effective in preserving ischemic tissue by facilitating healing of ulcers or limited amputations. Femoral-popliteal bypass grafting in the presence of advanced ischemia is capable of improving the quality of life for many of these patients.

Adult↗

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↗

An unusual variant of membranous nephropathy with abundant crescent formation and recurrence in the transplanted kidney.

A patient with what initially appeared to be a typical membranous nephropathy had a progressive course to renal failure, nephrectomy, and transplantation. The nephrectomy specimen revealed abundant glomerular crescents and capsular synechiae. Post-transplantation the patient again developed a membranous nephropathy with florid crescents. Radioimmunoassay and indirect immunofluorescence tests failed to reveal anti-glomerular basement membrane antibody in the serum or kidney. It appears that there is a form of membranous nephropathy with crescent formation, unrelated to anti-GBM antibody, which has the capacity to recur after transplantation.

Adult↗

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↗