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Biomedical subjects

A J Matas

Publications and source records attributed to A J Matas.

At least 397 records · Page 22Linked to original sources
PubMed1975

Chronic antigenic stimulation, herpesvirus infection, and cancer in transplant recipients.

An increased incidence of malignancy has been reported in transplant recipients. The pathogenesis of this increase was originally attributed to immunosuppressive therapy. However, not all tumours are increased in proportion to their occurrence in the general population-75% of reported tumours are lymphorproliferative or carcinoma of the skin, lip, or cervix. This cannot be explained by impaired immunosurveillance, and alternative hypotheses must be considered. 90% of transplant recipients develop clinical or serological evidence of herpesvirus infection. Herpesviruses have been implicated in the pathogenesis of lymphorproliferative tumours and carcinoma of the skin and cervix. They can remain in latent form and be reactivated by allogeneic stimulation and/or immunosuppression. These viruses localise to skin, cervix, and neural tissue-i.e., exactly those sites where cancer develops in transplant patients. Herpesvirus infections in association with the presence of an allogeneic graft in an immunosuppressed patient may be responsible for the increased incidence of both lymphoproliferative tumours and carcinoma of the skin, lip, and cervix in the transplant recipient.

Antibodies, Viral↗
PubMed1975

Increased incidence of malignancy during chronic renal failure.

The incidence of cancer in 646 dialysis/transplant patients before uraemia developed, during the period of progressive uraemia, and post-transplantation was compared. 10 tumours (3 breast, 2 kidney, 1 leukaemia, 1 lung, 1 insulinoma, 1 thyroid, 1 cervix in situ) developed in 9 patients during the period of progressive uraemia, a significant increase over the expected number in the age-matched general population. 6 of these patients have received transplants and have no evidence of recurrent disease 6 months to 4 years post-transplantation. 11 de-novo tumours have developed in 530 transplant recipients (4 cervix in situ, 2 skin, 2 reticulum-cell sarcoma, 1 lip, 1 dysgerminoma, 1 colon)--a significant increase over the age-matched general population. The cancers in the uraemic patients are relatively common types of mesenchymal tumours while the cancers in the transplant recipients are epithelial and lymphoproliferative. This difference may reflect the presence of the graft in the transplant patient or may be due to different patterns of immunosuppression in these two populations.

Adolescent↗
PubMed1975

Successful renal transplantation in patients with prior history of malignancy.

Eleven selected patients with a history of cancer have received renal transplants. In three patients the malignancies were diagnosed and treated before renal failure developed. Two patients underwent bilateral nephrectomies for the treatment of bilateral renal malignancy. In six patients the malignancy developed while they were uremic, and they received transplants after treatment of the tumor. Recurrent tumor developed in only one of the 11 (9 per cent) patients after receiving the transplant. Thus, patients with a history of malignancy can receive a transplant without accelerating growth of the tumor. We recommend a minimum period of one year between tumor treatment and transplantation to observe for tumor recurrences or metastases. A longer period of observation may be necessary in patients who have tumors with a poorer prognosis.

Adult↗
PubMed1975

Lethal complications of bilateral nephrectomy and splenectomy in hemodialyzed patients.

Routine bilateral nephrectomy and splenectomy (BNS) in uremic patients before transplantation are relatively safe procedures except when there is pre-existing sepsis, diabetes, or severe hypertension. A review of 421 patients undergoing routine pretransplantation BNS reveals that death before transplantation occurs in two definable groups of patients. In our series, the first group, those with juvenile onset diabetes, have a 15.4 per cent pretransplantation mortality (9.6 per cent operative and 5.8 per cent nonoperative) while being maintained on hemodialysis and awaiting transplantation. The second group, nondiabetic patients with other preoperatively definable risk factors such as severe hypertension and infected kidneys, had a 3.25 per cent pretransplantation mortality (1.9 per cent operative and 1.25 per cent nonoperative) while on hemodialysis. Paradoxically, these same factors are used as absolute criteria for pretransplantation nephrectomy at institutions where this operation is not a routine part of the pretransplantation regimen.

Cardiovascular Diseases↗
PubMedDate not supplied

Pre-emptive renal transplantation.

We report our experience with pre-emptive renal transplantation and review the literature. While eliminating the cost, complications and inconvenience of dialysis, transplantation prior to dialysis therapy can be performed safely and effectively as it does not pose any additional immunological hazards to allograft outcome. It is safe regardless of the immunosuppressive agents employed and is successful without early rejection even in the nonuremic state.

Blood Transfusion↗
PubMedDate not supplied

Cardiac xenografting in the pig-to-rhesus monkey model: manipulation of antiendothelial antibody prolongs survival.

Transplantation of immediately vascularized grafts across species barriers in which preformed cytotoxic antibodies exist, otherwise known as discordant combinations, has uniformly resulted in hyperacute rejection. We studied how well plasma exchange and perfusion through organs removes preformed immunoglobulin M cytotoxic antibodies and prolongs survival of a porcine heart heterotopically transplanted into a rhesus monkey. With the use of plasma exchange or absorption of antibodies by porcine kidney perfusion with or without immunosuppression, graft survival was prolonged, although antibody-mediated rejection ultimately occurred. In one case in which plasma exchange, kidney perfusion, and immunosuppression were combined, a functioning pig heart survived in a rhesus monkey for 8 days without evidence of rejection. The animal was killed on day 8 according to protocol because of a wound dehiscence. With this animal we were able to demonstrate that circulating antibodies against graft endothelium had bound to the graft endothelium without inducing rejection, a process referred to as accommodation. In this case, despite the presence of antiendothelial antibodies, complement did not appear to be activated, and fibrin thrombi did not form. Although we have achieved this rejection-free survival only in one animal, this case suggests that it may be possible to maintain xenotransplants in discordant species without rejection if preformed antibodies are appropriately lowered or altered during the initial period of graft implantation.

Animals↗
PubMedDate not supplied

Safe and effective plasma exchange to remove antibodies prior to xenogeneic heart transplantation in small primates.

The ability of an on-line, rapid plasma exchange (PE) system to remove circulating antibodies in preparation for xenogeneic heart transplantation was studied. Plasma exchanges were performed 27 times on 13 rhesus monkeys weighing from 6.5 to 12.0 kg, using systemic heparinization, without untoward effects. Blood flow rates of 22-72 ml/min resulted in plasma collection rates of 7-22.5 ml/min. Serum immunoglobulin levels were decreased by more than 90%, and specific antiendothelial xenoreactive IgM was completely removed after two plasma exchanges. Transferrin levels were decreased 85-95%, and complement levels fell by greater than 80%. Platelets were partially conserved, with removal rates of 18-60%. All factors returned to normal ranges within 48 hours and no bleeding complications were encountered. When antiendothelial antibodies were removed in this manner, survival of a pig heart transplanted into a rhesus monkey was extended to 12 hours, from a baseline of 2 hours, without treatment.

Animals↗