Search PubMed⌕ Search

Biomedical subjects

R L Kirkman

Publications and source records attributed to R L Kirkman.

At least 55 records · Page 3Linked to original sources
PubMed1989

Prophylactic use of monoclonal anti-IL-2 receptor antibody in cadaveric renal transplantation.

In vivo administration of an anti-interleukin-2 (anti-IL-2) receptor monoclonal antibody is a potential new therapy for prevention of allograft rejection of a freshly transplanted organ. Such an approach is more selective than targeting all T cells, or even the CD4 or CD8 major subsets, because only the very recently activated cells should be affected. A clinical trial of anti-Tac monoclonal antibody is in progress in which 20 mg of the immunoglobulin G 2a (lgG2a) antibody is administered intravenously daily for 10 days after cadaveric renal transplantation. Combinations with and without azathioprine, and with varying doses of cyclosporine with prednisone, are being evaluated in a randomized trial. Results to date show a significant immunosuppressive effect of anti-Tac, as measured by a reduced incidence and later onset of acute rejection episodes compared with cyclosporine plus prednisone or cyclosporine plus azathioprine plus prednisone. Removal or cytodestruction of IL-2-receptor positive cells from the peripheral blood does not occur to any major degree, even though serum levels of the antibody are always detectable. In addition, functional studies of MLR, CML, and suppressor cell generation 4 days after cessation of anti-Tac administration show no significant difference between treated and control groups The effect of anti-Tac seems, therefore, to be limited to inhibition of IL-2-mediated T-cell growth during the period of administration, with recovery after a few days' lag period.

Antibodies, Monoclonal↗
PubMed1989

The role of a primate model of renal transplantation in the development of new monoclonal antibodies.

In recent years, a detailed understanding of the cellular and molecular basis of the immune response has been achieved. These advances, coupled with the technology for producing monoclonal antibodies, have made possible to consider highly specific and potentially powerful methods of immunosuppressive treatment. This promise of potent and specific treatment has not been entirely fulfilled on clinical practice. A preclinical nonhuman primate model of renal transplantation is described. The model has been used to investigate two monoclonal anti-IL-2 receptor antibodies, one of which was found to be effective. Anti-Tac, an lgG2a mouse antihuman monoclonal antibody, prolongs graft survival in cynomolgus monkeys from 12 to 19 days. The role of such a model in bringing new monoclonal antibodies to the clinic is described.

Animals↗
PubMed1987

Use of cytomegalovirus immune globulin to prevent cytomegalovirus disease in renal-transplant recipients.

We undertook a prospective randomized trial to examine whether an intravenous cytomegalovirus (CMV) immune globulin would prevent primary CMV disease in renal-transplant recipients. Fifty-nine CMV-seronegative patients who received kidneys from donors who had antibodies against CMV were assigned to receive either intravenous CMV immune globulin or no treatment. The immune globulin was administered in multiple doses over the first four months after transplantation. The incidence of virologically confirmed CMV-associated syndromes was reduced from 60 percent in controls to 21 percent in recipients of CMV immune globulin (P less than 0.01). Fungal or parasitic superinfections were not seen in globulin recipients but occurred in 20 percent of controls (P = 0.05). Only 4 percent of globulin recipients had marked leukopenia (reflecting serious CMV disease), as compared with 37 percent of the controls (P less than 0.01). There was a concomitant but not statistically significant reduction in the incidence of CMV pneumonia (17 percent of controls as compared with 4 percent of globulin recipients). A significant reduction in serious CMV-associated disease was observed even when patients were stratified according to therapy for transplant rejection (P = 0.04). We observed no effect of immune globulin on rates of viral isolation or seroconversion, suggesting that treated patients often harbored the virus but that clinically evident disease was much less likely to develop in them. We conclude that CMV immune globulin provides effective prophylaxis in renal-transplant recipients at risk for primary CMV disease.

Adult↗
PubMed1987

Metabolic aspects of small bowel transplantation in inbred rats.

An inbred rat model of small bowel transplantation was used to study the metabolic consequences of systemic venous drainage of the graft. Lewis rats received either Lewis (isograft) or Lewis X Brown Norway F1 (allograft) small bowel grafts. Venous drainage of the isografts was to either the portal vein or the inferior vena cava. Allograft recipients underwent systemic venous drainage and were treated with a 4-week course of tapering cyclosporine. Ammonia levels in systemically drained isografts (108 +/- 5 microM/100 ml) were more than twice those in portally drained isografts (38 +/- 3, P less than 0.001), while amino acid analysis showed significant elevations in glycine, serine, asparagine, histidine, phenylalanine, and tyrosine. Ammonia levels decreased and amino acid alterations were generally corrected when animals were fed a modified protein diet low in aromatic and high in branched chain amino acids. Recipients of both systemically and portally drained isografts grew normally, while weight gain in allograft recipients was impaired. We conclude that systemic venous drainage of small bowel grafts results in altered ammonia and amino acid levels that resemble those found in models of hepatic encephalopathy; these changes can be significantly ameliorated by dietary modification; and the compromised growth seen in systemically drained allografted animals results from chronic rejection and/or cyclosporine rather than the partial porto-systemic shunt.

Amino Acids↗