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Biomedical subjects

F T Thomas

Publications and source records attributed to F T Thomas.

At least 55 records · Page 3Linked to original sources
PubMed1990

Prophylactic therapy for rejection after cardiac transplantation. A comparison of rabbit antithymocyte globulin and OKT3.

The value of prophylactic monoclonal or polyclonal antibody therapy early after cardiac transplantation is controversial. Between Jan. 1, 1987, and July 1, 1988, 32 consecutive patients underwent cardiac transplantation (cyclosporine, azathioprine, and prednisone maintenance therapy) with either early prophylactic rabbit antithymocyte globulin (n = 17) or monoclonal OKT3 (Ortho Diagnostic Systems, Inc., Raritan, N.J.) (10 days) (n = 15). Follow-up was through Sept. 1, 1988, for morbid events and through Jan. 1, 1989, for survival. All patients (100%) survived the study period (follow-up of 6 to 24 months). The efficacy of rabbit antithymocyte globulin and OKT3 prophylaxis was similar regarding median time (days) to first rejection (16 versus 21 days, p = 0.5), number of rejection episodes during first 2 months (1.5 versus 1.3 days, p = 0.8), and freedom from rejection at 2 months (18% versus 27%, p = 0.8). Early infections were slightly less common in the rabbit antithymocyte globulin group than the OKT3 group (median time to first infection: 318 versus 250 days, p = 0.5; freedom from rejection at 2 months: 82% versus 64%, p = 0.21), although differences were likely due to chance. Cytomegalovirus syndrome was common, with one case of cytomegalovirus pneumonia. T-cell markers during OKT3 treatment did not predict subsequent rejection (within 2 weeks after OKT3) as assessed by mean T3-lymphocyte count during OKT3 use (p = 0.3) or T3-lymphocyte count during the last 3 days of OKT3 use (p = 0.4). Inferences: (1) Prophylactic rabbit antithymocyte globulin or OKT3 with triple-drug immunosuppression yields excellent intermediate survival after heart transplantation. (2) These protocols for rabbit antithymocyte globulin and OKT3 provide similar protection against early rejection with a relatively low risk of early infection. (3) T-cell markers do not predict early rejection after OKT3.

Adult↗
PubMed1990

The vascular endothelial cell is central to xenogeneic immune reactivity.

With the demand for organ transplants increasing, xenograft transplantation is being considered. A major obstacle to a solution to fulfilling this demand is xenograft rejection. Histologic evidence indicates that the vascular endothelial cell (VEC) is involved in both humoral and cellular aspects of xenograft rejection. To study this phenomenon murine VEC and splenocytes were used in a mixed lymphocyte/endothelial cell culture and in a mixed lymphocyte culture with human peripheral blood mononuclear cells as responders. The VEC is a much better stimulator than the splenocyte. Removal of macrophages and B cells from the human peripheral blood mononuclear cells has no effect on the response to the VEC. The VEC acts as a target for humoral responses in the complement-dependent cytotoxicity and the antibody-dependent cell-mediated cytotoxicity. The VEC is killed in these two assays, which indicates the importance of the VEC in humoral rejection. These data indicate that the VEC is an important cell in xenogeneic immune reaction and may be pivotal in xenograft rejection.

Animals↗
PubMed1989

Specific unresponsiveness to skin allografts in burns.

We have examined the potential to provide long-term or even permanent wound coverage in a mouse model of a 30% total body surface area burn using skin allografts. Treatment of the recipient mouse with rabbit anti-mouse thymocyte serum (ATS) followed by donor bone marrow infusion induces a state of specific unresponsiveness to the skin allograft without the need for chronic immunosuppression. Specifically, a B6AF1 mouse receives a burn on Day -2 relative to grafting, ATS on Day -1, and Day +2, a skin allograft from a C3H/He mouse on Day 0, and infusion of C3H/He donor bone marrow on Day +6. We studied three groups of burned mice: Group I, allograft control (n = 5); Group II, allograft plus ATS (n = 12); and Group III, allograft plus ATS and bone marrow infusion (n = 15). Mean graft survival was compared using a one-way analysis of variance and a Student-Newman-Keuls post hoc test. There was no statistical difference in animal mortality among any of the three groups, and there was no evidence of infectious morbidity. Mean skin allograft survival was as follows: Group I, 9 days; Group II, 29 days; and Group III, 66 days (P less than 0.05 vs Group I and II). Nine animals in Group III had intact hair bearing grafts at 90 days when the study was terminated. This study suggests the potential use of induced specific unresponsiveness to skin allografts for wound coverage in thermal injury without use of chronic immunosuppression. In our animal study this was accomplished without increased mortality or apparent infectious morbidity.

Animals↗
PubMed1984

The Greenville gastric bypass. Progress report at 3 years.

Two hundred and ten morbidly obese patients underwent a standardized gastric bypass procedure between February 1980 and November 1983. We conclude, based on 100% follow-up, that the operation is safe (operative mortality--1%, significant complications--10%) and effective (reoperation rate--4%). Only one patient failed to lose more than 25% of preoperative weight. The operation produced a mean weight loss in the group from 289 pounds (202-505) before surgery to 176 pounds (118-308) at 18 months after surgery. Stated as "per cent of ideal weight," patients lost from a preoperative mean of 214% (153-350) to 130% (88-189) at 18 months. Maximum weight loss was reached by 18 months after the procedure and was maintained during 36 months of observation in over 95% of patients. When patients were divided into four groups according to preoperative weight, weight loss occurred at a roughly similar rate, but heavier patients, although they lost more weight, plateaued at a higher weight than patients originally less obese. Striking and objective benefits were seen in patients with diabetes, hypertension, heart disease, and pulmonary insufficiency.

Adolescent↗
PubMed1983

Long-term incompatible kidney survival in outbred higher primates without chronic immunosuppression.

Transplantation between non-identical humans has been limited by the requirement for chronic immunosuppression (CI). This study demonstrates in a nonhuman primate model that long-term acceptance of incompatible kidney allografts can be achieved without the use of CI. Following incompatible kidney transplantation, rhesus monkey recipients were given a 5-day course of clinical rabbit antithymocyte globulin (RATG). On day 12, unfractionated donor bone marrow (BM) was infused intravenously. Recipients were monitored for T-cell levels and T-cell subset levels with monoclonal antibodies and for responses in one way MLR. Graft survival in untreated control animals was 9.2 +/- 2.8 days. In six animals given RATG only, all died of rejection at a mean 35.8 +/- 5.7 days. Of five animals given RATG and donor BM (mean 2.5 RhLA mismatches, mean MLC 12.7), four are alive at 150 days, 248 days, 342 days, and 401 days (median 248 days). The ATG-BM infused group showed a prolonged imbalance of their OKT4/OKT8 cell ratio and cellular suppression of MLR responsiveness. The long-term survival obtained in these outbred primates is apparently due to a synergistic immunoregulatory effect induced by the RATG and donor BM. The model described is apparently the first report of long-term survival of outbred higher primates without CI and may represent a technique for producing tolerance without CI in the human.

Animals↗
PubMed1983

A prostaglandin-dependent immunoregulatory mechanism activated by in vivo administration of antithymocyte globulin.

The mechanism responsible for the profound and enduring immunosuppressive action of antithymocyte globulin (ATG) is not well understood. In a primate model, we found that a 5-day rabbit ATG (RATG treatment course activates a prostaglandin (PG)-dependent suppressor cell mechanism that persists for several months. Groups of normal rhesus monkey skin allograft recipients, kidney allograft recipients, or nontransplant control animals received either RATG or no immunosuppression. The peripheral blood mononuclear cell (PBMC) population was longitudinally monitored for (1) percentage of total T cells, helper cells, and suppressor/cytotoxic T cell subsets with the monoclonal antibodies Leu-5, OKT4, and CKT8, respectively, and (2) phytohemagglutinin (PHA)-induced lymphocyte proliferative responses (LPR). The nonimmunosuppressed control groups showed no significant changes in any of these parameters. In contrast, PBMCs from all RATG-treated monkeys developed a persistent imbalance in the ratio of OKT4+ and OKT8+ subsets. Their PBMCs became unresponsive to PHA and remained unresponsive (less than 20% of control level) for at least 3 months, although total T cell counts recovered within 2 to 3 weeks after cessation of RATG. Addition of PG synthetase inhibitors indomethacin. RO-20-5720, and tolmetin caused a significant, dose-dependent recovery of LPR that was completely inhibited by exogenous PGE2 at 1 X 10(-8) M. PBMCs from RATG-treated monkeys caused a dose-dependent suppression of the normal PHA response, and this suppressor cell activity was blocked by indomethacin. PHA responses of nonimmunosuppressed control groups were not increased significantly in the presence of PG synthetase inhibitors, were less sensitive to suppression by PGE2, and did not exhibit suppressor cell activity. These data suggest that the prolonged depression in LPR after RATG treatment is due to an active PG-dependent suppressor cell mechanism and provide a new concept to explain the immunosuppressive action of RATG.

Animals↗
PubMed1982

The effectiveness of gastric bypass over gastric partition in morbid obesity: consequence of distal gastric and duodenal exclusion.

Eighty-seven morbidly obese patients were prospectively randomized to two operations: gastric bypass was performed on 42 and gastric partition on 45. Gastric bypass proved to be more effective; gastric bypass patients lost 15% more of their original weight at 12 months and 21% more at 18 months. There were no failures in the gastric bypass group; 28 of the 45 operations failed in the gastric partition group. An additional 60 patients underwent gastric bypass since the completion of the study. In the total series of 147 patients who underwent gastric bypass or gastric partition, there was no mortality, and the surgical complication rate was 12%. Because the gastric pouches and the anastomoses were similar in the two operations, the superiority of the gastric bypass may well be due to a heretofore unexplained effect of distal gastric and duodenal exclusion.

Adult↗
PubMed1982

Suppressor cells in rhesus monkeys treated with antithymocyte globulin.

Treatment of rhesus monkey skin allograft recipients with a brief course of rabbit antithymocyte globulin (ATG) produces an enduring immunosuppressive effect on the cellular immune system. Despite early recovery of circulating T cells, in vitro mitogen-induced lymphoproliferative responses of peripheral blood mononuclear cells (PBMCs) remain abnormally depressed for months. In this study we show that depressed mitogen-induced lymphoproliferative responses in these animals are attributable to regulatory effects of adherent PBMCs. Removal of the adherent fraction of PBMCs on Sephadex G-10 produced a significant restoration of the mitogen-induced lymphoproliferative responses in ATG-treated monkeys. Addition of the prostaglandin synthetase inhibitor indomethacin to cultures of unfractionated PBMCs from these animals also caused a significant recovery of the lymphoproliferative response. Indomethacin did not enhance the response of control animals or the response of the nonadherent PBMC fraction of ATG-treated animals. These data suggest that a prostaglandin-dependent mechanism is involved in the suppressive action of the adherent cells. PBMCs from ATG-treated monkeys cocultured with normal cryopreserved autologous cells induced a dose-dependent suppression in the response to both concanavalin A (Con A) and phytohemagglutinin (PHA). The suppressive activity depended upon the adherent cell fraction and was found to be resistant to low-dose gamma irradiation. These data indicate that administration of rabbit ATG induces nonspecific suppressor cells in the rhesus monkey. Preliminary characterization studies suggest the involvement of suppressor monocytes. The possible role of this suppressor cell system in the immunosuppressive action of rabbit ATG is discussed.

Animals↗
PubMed1979

Improved immunosuppression for cardiac transplantation: immune monitoring and individualized modulation of recipient immunity by in vitro testing.

These studies demonstrate that immune monitoring and individualized modulation of recipient immune reactivity using a quality-controlled preparation of rabbit antithymocyte globulin can improve results of cardiac transplantation. The most valuable assay in individualizing drug doses was the serial measurement of T-cell levels using a complete lymphocyte profile technique and monitoring with phytohemagglutinin to rule out false low T-cell levels. Using this system, the incidence and severity of early rejections were markedly reduced and no grafts were lost to rejection in the first month. The recent first-year graft survival has been about 60%, an improvement largely related to a reduction in early rejection and infection. This technique of immunosuppression appears quite promising for improving the results of future cardiac transplantations.

Antilymphocyte Serum↗
PubMed1979

Immunological monitoring as a guide to the management of transplant recipients.

Immunological monitoring assays are of current value in the management of transplant recipients. These assays allow the pre-transplant quantitation of both donor-recipient histocompatibility and recipient "responder status." In addition, these assays allow the individualization of immunosuppression, permitting a more uniform and effective immunosuppression in the difficult early post-transplant period. Individualized modulation of recipient immune reactivity avoids the documented pitfalls of conventional stereotyped suppression and permits better abrogation of acute rejection responses and lesser rates of serious infections consequent to excessive immune suppression. Immunological monitoring of long-surviving recipients permits early detection of immune reactivity which often culminates in clinical chronic rejection, as well as permits the quantitation of immune facilitory mechanisms (reduced capability to generate anti-donor cytotoxic T cells and/or cellular suppressor mechanisms) that indicate an immune milieu conductive to long-term graft survival. The primary limitations to the more widespread use of immunological monitoring assays at present are the need for more consensual validations of the utility of these assays in different laboratories, more standardization and better controls of techniques, and improvement in the technology of the assays to permit rapid, reproducible, and accurate results with a lesser expenditure of laboratory time and money and greater economy in demands for recipient blood and donor tissue. Finally, immunological monitoring assays are notable for the great promise they offer in terms of immunobiological probes to dissect mechanisms of rejection, mechanisms of graft facilitation, mechanisms of action of immunosuppressive agents, and mechanisms by which empirical technology of recipient pre-treatment may condition the host to better acceptance of an incompatible graft.

Animals↗