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Biomedical subjects

R Y Calne

Publications and source records attributed to R Y Calne.

At least 271 records · Page 15Linked to original sources

[Action of cyclosporin A and cytimun on the survival time of accessory heart transplants (author's transl)].

The new immunosuppressive substances Cyclosporin A (group A = 15 mg) and Cytimun = ASTA 5122 (group B = 15 mg, group C = 5 mg) were tested in rats that received accessory cervical heart transplants. A syngeneic (DA leads to DA) and a strongly allogeneic (PVG leads to DA) strain combination served as controls of operative and immunogenetic parameters. Whereas Cyclosporin A (group A) brought about a local transplant tolerance in 90% of cases, at a dosage of 15 mg/kg per day (group B), Cytimun led in 88% of cases to lethal intoxication of the recipients. At a dosage of 5 mg/kg per day (group C), 67% of the animals survived; however, they showed electrocardiographic evidence of possible temporary rejection crises between the 5th and the 13th day.

Animals↗

Cyclosporin A initially as the only immunosuppressant in 34 recipients of cadaveric organs: 32 kidneys, 2 pancreases, and 2 livers.

34 patients treated with cyclosporin A received 36 cadaveric organ allografts (32 kidneys, 2 pancreases, and 2 livers), 26 kidneys are still supporting life, 3 after more than a year; the pancreases and livers are also functioning. 20 patients are not receiving steroids, and 15 of these have not had any additional immunosuppressive agents. In these patients infectious complications have not been severe, but a gastroduodenal lymphoma has developed in 1 patient. 6 patients were given 'Cytimum' (a cyclophosphamide derivative) and steroids in addition to cyclosporin A: 5 of these died of infections and 1 also had a lymphoma. 11 patients received additional steroids: 1 of these died from septicaemia and lymphoma. Nephrotoxicity can be avoided by perioperative hydration and forced diuresis. Cyclosporin A is effective on its own and is a very potent immunosuppressive drug. Additional immunosuppressive agents may lead to severe complications.

Adult↗

Use of partial cardiopulmonary bypass during the anhepatic phase of orthotopic liver grafting.

Femoro-femoral partial cardiopulmonary bypass has been used in two patients under going orthotopic liver allografting who had severe cardiovascular disturbances on trial clamping of their venae cavae. Flows of 2-3 litres/min resulted in satisfactory cardiovascular control during the anhepatic phase in each ase. A third patient who tolerated caval clamping withstood the grafting without bypass. Having bypass available for use in critical cases could increase the safety of orthotopic liver transplantation.

Adult↗

The treatment of major liver trauma by primary packing with transfer of the patient for definitive treatment.

Four patients are reported in whom massive haemorrhage from severe hepatic trauma was managed initially by conservative surgery and packing. The patients were then transferred by ambulance to Addenbrooke's Hospital where further treatment involved elective surgery and removal of packs. All 4 patients were discharged from hospital and have made full recoveries. It is felt that the management of liver trauma should be to do the minimum that is necessary to staunch bleeding, by suture, arterial ligation, lobectomy, resectional debridement or simply by packing. This allows the patient's haemodynamic state to be restored to normal before further surgery is attempted.

Adolescent↗

Technique of organ removal and fate of kidney grafts from liver donors.

The fate of 42 kidney grafts taken from heart-beating, ventilated donors at the same time as removal of the liver for allografting is reported, and is compared with 50 kidney grafts taken from heart-beating, ventilated donors whose ventilators were electively switched off either during or immediately before kidney removal. The fate of 32 kidney grafts taken from donors classified as "dead on arrival" at the admitting hospital is also reported. Onset of life-supporting graft function was significantly earlier among kidneys from the "liver donor" group. Consequently, immediate postoperative dialysis requirements were significantly less in recipients of this group of kidneys. Early graft survival, the incidence of graft primary nonfunction, failure of first and second kidney grafts, and recipient survival were not significantly different when comparing liver donor and "ventilator switch off" kidneys. No constant relationship was apparent in any donor group between graft fate and the anoxic and ischaemic times the graft was exposed to during organ removal and reimplantation.

Adolescent↗

Pharmacological immunosuppression in clinical organ grafting. Observations on four agents: cyclosporin A, Asta 5122 (cytimun), lambda carrageenan and promethazine hydrochloride.

In this article I have attempted to summarize experiments on four agents investigated for immunosuppressive activity in experimental and clinical organ grafting. The difficulty of finding a suitable laboratory model relevant to man has been demonstrated in this experience. A cyclophosphamide-derivative, Asta-5122 (cytimun), has only a marginally superior immunosuppressive activity in a dog with a renal allograft compared with cyclophosphamide and is much inferior to azathioprine. This agent, however, appears to be valuable in clinical practice in patients with liver grafts. A combination of lambda carrageenan, promethazine hydrochloride and imuran has profound immunosuppressive activity in the same canine model, but proved to be both ineffective and potentially toxic in a limited trial in man. The fungal cyclic peptide, cyclosporin A, has been shown to be an extremely powerful immunosuppressive agent and remarkably non-toxic in dogs with renal allografts and pigs with orthotopic heart grafts. This agent is currently being investigated as an immunosuppressant in patients with organ grafts.

Adult↗

Orthotopic liver transplantation in the rat. Technique using cuff for portal vein anastomosis and biliary drainage.

In orthotopic liver transplantation in the rat, cuff techniques have been developed for anastomoses of the portal vein and bile duct. These techniques have shortened the clamping time of the portal vein and have resulted in fewer biliary complications improving survival of the liver graft. Eighty-three per cent of the grafted animals have survived for 1 week and several animals have survived for more than 6 months. We believe that use of the cuff method technically simplifies microvascular anastomoses. It may be particularly useful for anastomosis of the portal vein after machine preservation of the donor rat liver.

Animals↗