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Biomedical subjects

W P Homan

Publications and source records attributed to W P Homan.

At least 19 recordsLinked to original sources
PubMed1981

Canine intestinal intussusception following renal and pancreatic transplantation.

In 138 mongrel dogs given renal transplants, 10 developed postoperative intussusceptions. The sites were jejunojejunal (seven), ileo-ileal (two) and ileocolic (one). In 30 puppies given intrasplenic autografts of dispersed pancreatic fragments after total pancreatectomy, five developed jejunojejunal intussusceptions. Presenting signs included vomiting, failure to eat, periodic attacks of pain, straining with the passage of bloodstained mucous, dehydration, weight loss, abdominal wall rigidity and an abdominal mass. The majority of dogs presented within the first seven days following transplantation, occasionally as late as the third week. Early operative intervention was essential to save the dogs and at laparotomy eight of nine intussusceptions were successfully reduced manually; one small bowel resection was performed for irreducibility. Recurrence was not observed in this series but reoperation in the puppies was invariably fatal. Factors contributing to the development of intussusception in the puppies included round worm infestation, recent dietary change following weaning, malabsorption and diarrhoea due to pancreatic insufficiency following pancreatectomy and respiratory infections suggesting an infective origin for the intussusceptions.

Animals↗
PubMed1981

Prolongation of cardiac xenograft survival in rats receiving cyclosporin A.

The effect of cyclosporin A was tested in a heterotopic cardiac xenograft model, in which hamster hearts were implanted into LEW rats. Despite the presence of low titers of rat anti-hamster lymphocytotoxic antibodies immediate rejection of the hamster hearts did not occur, suggesting that this model represented a xenogeneic barrier of moderate strength, compatible with the close relationship of the two species. Cyclosporin A, in doses approaching toxic levels of 35 or 50 mg/kg/day for 14 days, prolonged function of the cardiac xenografts for median survival times of 21 and 11 days, respectively, in contrast to the median survival of 2 days in untreated recipients. The lymphocytotoxic antibody response of the LEW rats to the cardiac xenograft was suppressed, even in doses that did not prolong graft survival. Only the dose of 50 mg/kg/day produced any significant alteration in the histological features of rejection in the cardiac xenografts. Although cyclosporin A markedly prolonged survival of cardiac xenografts between these two closely related species, the requirement of virtually toxic levels of the drug for an effect do not suggest that this drug will be of value in transplantation of vascularized organ xenografts.

Animals↗
PubMed1981

Prolongation of renal allograft survival in the rat by pretreatment with donor antigen and cyclosporin A.

Pretreatment of LEW rats with cyclosporin A (10 mg/kg/day orally for 14 days) plus 10(8) DA or (DA X LEW)F1 spleen lymphocytes on two occasions markedly prolonged the survival of subsequent DA renal allografts. The lymphocytotoxic antibody response was suppressed completely and renal biopsies showed a marked mononuclear cell infiltrate, but no other manifestations of rejection. Neither pretreatment with cyclosporin A alone nor pretreatment with splenic lymphocytes alone had any effect on the subsequent immune reaction. The immunosuppressive effect generated was dependent upon the dose of lymphocytes given, because pretreatment with 10(7) cells on two occasions plus cyclosporin A was relatively ineffective at prolonging renal allograft survival. Pretreatment with 10(8) (DA X LEW)F1 spleen cells plus cyclosporin A was also an effective combination, and ruled out the possibility that graft-versus-host (GVH) disease was responsible for the observed immunosuppression. This pretreatment protocol exhibited specificity in terms of rejection of a third-party (PVG) renal allograft, but not in terms of the lymphocytotoxic antibody response to this graft. Chimerism was not detected in long-term surviving animals using a 51Cr release assay. When pretreatment was performed in LEW rats with a DA skin allograft plus cyclosporin A, a subsequent DA renal allograft was rejected normally, in combination with the skin graft. These findings suggest that clonal deletion had not occurred in these pretreatment protocols, but that a shift in immunoregulatory mechanisms was responsible for the long survival. There are possible clinical implications for the use of pretreatment schedules using donor antigen and cyclosporin A.

Animals↗
PubMed1981

A technique for transplanting pancreatic islets as a vascularized graft and prevention of rejection with cyclosporin A.

Transplants of isolated allogeneic pancreatic islets behave as if extremely immunogenic but vascularized segmental pancreatic allografts do not evoke such a rapid rejection of islet tissue. We have transplanted rat pancreatic islets as a vascularized graft by implanting isolated islets under the renal capsule of a syngeneic diabetic rat and, after successful reversal of diabetes, a composite graft of kidney and islets was transplanted into an allogeneic diabetic host. Cyclosporin A was used to suppress rejection of the allografts in doses that have previously been shown to completely suppress rejection of renal allografts and delay rejection of vascularized segmental pancreatic allografts. This strategy produced indefinite survival of the allogeneic isolated pancreatic islets.

Animals↗
PubMed1980

Interaction of cyclosporin A with antilymphocyte serum and with enhancing serum for the suppression of renal allograft rejection in the rat.

The interactions between antilymphocyte serum (ALS) and cyclosporin A and between enhancing serum cyclosporin A were investigated in a DA to Lewis rat renal allograft model. Subtherapeutic doses of cyclosporin A (2 mg/kg/day), when combined with enhancing serum, produced no consistently beneficial effect in animal survival. A short course of cyclosporin A in therapeutic doses (5 mg/kg/day for 4 days) with enhancing serum was also no better than either agent used alone in prolonging rat survival. Subtherapeutic doses of ALS along with subtherapeutic doses of cyclosporin A (2 mg/kg/day) showed a favorable interaction, prolonging animal survival to a median of 59 days. Combination of immunosuppressive agents did not improve the histological picture of allograft rejection when compared to that seen when the agents were used individually. That cyclosporin A plus ALS show a favorable interaction, whereas cyclosporin A plus enhancing serum does not, may indicate that cyclosporin A and enhancing serum operate on the same portion of the immune response.

Animals↗
PubMed1980

Studies on the immunosuppressive properties of cyclosporin a in rats receiving renal allografts.

The immunosuppressive effects of cyclosporin A were tested in a DA (RT-1a) to Lewis (RT-1(1) rat renal allograft model, which represents a very strong histocompatibility barrier. Dose-response studies established that oral doses of 5 mg/kg/day or higher gave complete suppression of rejection, while oral doses of 2 mg/kg/day or lower were without effect. Intravenous administration of the drug approximately doubled its potency. Time studies showed that the period of administration was also critical, with a 7- or 14-day treatment course with 5 mg/kg/day orally giving prolonged graft survival, while a 4-day course was without effect. Large doses (up to 25 mg/kg/day orally) from day 4 after transplantation did not prolong graft survival, suggesting that cyclosporin A has no effect on an established rejection response. It was found that the lymphocytotoxin response to the graft was markedly suppressed by doses of cyclosporin A which maintained normal graft function, while lower doses had little or no effect on the lymphocytotoxin response. A cell-mediated immunity assay showed a substantial response, but one that was lower in amplitude from that of control animals. Histological study of 7th day allograft biopsies demonstrated essentially normal kidneys, except for a mild mononuclear cell infiltrate, at higher doses of cyclosporin. Lower doses of cyclosporin gave a picture of rejection no different from that seen in untreated controls. The LD50 of cyclosporin was found to lie between 50 and 100 mg/kg/day orally. Even the higher of these doses did not cause nephrotoxicity as determined biochemically and histologically.

Animals↗
PubMed1980

Effect of cyclosporin A upon second-set rejection of rat renal allografts.

With the use of a DA to LEW rat renal allograft model, the ability of cyclosporin A to influence a second-set rejection was investigated. Sensitization of LEW rats was accomplished by performing DA to LEW skin grafts 4 to 5 weeks before kidney allografting. Cyclosporin A was given to sensitized rats in doses of 10 or 25 mg/kg/day for 14 days from the time of renal transplantation. Neither dose was nearly as effective in prolonging kidney graft survival in sensitized rats as the 10 mg/kg/day dose was in prolonging kidney graft survival in unsensitized rats. In the 25 mg/kg/day dose, cyclosporin A was capable of suppressing antibody formation to the graft in sensitized recipients despite the presence of donor-specific antibodies at the time of renal transplantation. The 10 mg/kg/day dose of cyclosporin A did not, however, suppress antibody formation after renal transplantation in sensitized recipients. In both sensitized and unsensitized rats cyclosporin A was effective in ameliorating the histological findings of arterial fibrinoid necrosis and glomerular necrosis in the renal allografts. In neither sensitized nor unsensitized rats did cyclosporin A effect the mononuclear cell infiltration of the renal allograft.

Animals↗
PubMed1980

Studies on the effects of cyclosporin A upon renal allograft rejection in the dog.

Dose and time response studies of the new immunosuppressive agent, cyclosporin A, have been performed in a dog renal allograft model. Rejection of a renal allograft only occurred in one of six dogs receiving 20 mg/kg/day continuously, but in 10 of 11 dogs receiving 10 mg/kg/day. Doses of 10 or 20 mg/kg/day given for 2 or 3 weeks delayed rejection, but rejection occurred in all animals when the drug was stopped. This suggests that the drug does not produce clonal deletion of the lymphocytes engaged in the immune reaction against the graft, but merely their suppression. The histological picture of rejection was markedly improved by therapeutic doses of cyclosporin A. No consistent histological or biochemical evidence for heptatoxicity or nephrotoxicity was found even in the higher doses tested. One fatal and four non-fatal infectious complications were seen in 29 dogs receiving doses of 5 mg/kg/day or higher.

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