PubMed Health⌕ Search

Biomedical subjects

F L Delmonico

Publications and source records attributed to F L Delmonico.

At least 91 records · Page 5Linked to original sources
PubMed1984

Evolving use of OKT3 monoclonal antibody for treatment of renal allograft rejection.

OKT3, a monoclonal antibody reactive with a surface glycoprotein present on all postthymic T cells, was used to treat the initial acute episode of rejection in 30 recipients of cadaveric donor renal allografts. The first 16 patients received 1-5 mg daily for a period of 10-21 days during which the azathioprine and prednisone dosages were sharply reduced. Circulating T cells were eliminated within minutes after the first OKT3 infusion. T cells reactive with OKT3 remained depressed throughout the period of treatment, although a significant number of cells reactive with other T cells subset reagents became detectable after several days of OKT3 treatment. In all instances, the established rejection episode was reversed in 2-8 days without the addition of other immunosuppressive measures. Recurrent rejection occurred in 12 of 16 patients, but with further conventional immunosuppression, 50% of the renal allografts remain functional 20-44 months after transplantation. Fever, chills, and, in some instances, dyspnea following the first dose of OKT3 were the only side-effects observed. Most patients developed antiidiotypic or antimouse immunoglobulin antibodies without apparent clinical sequelae. In the subsequent 14 patients, modifications in the protocol included a steroid bolus prior to the first OKT3 infusion, limitation of therapy to 10 days, resumption of maintenance levels of azathioprine and prednisone prior to discontinuing OKT3, and addition of 3 i.v. doses of cyclophosphamide at the termination of treatment. Respiratory symptoms after the first infusion of the reagent have been eliminated. Antibody responses to OKT3 have been reduced, occurring in 38% as compared with 73% of patients treated previously. Recurrent rejection episodes observed in 8 of 14 patients have been reversible in all but one case. Allograft survival is 86% at 6-17 months posttransplantation. In the entire series of 30 OKT3-treated patients, only 4 grafts (13%) have been lost because of recurrent episodes of rejection.

Antibodies, Monoclonal↗
PubMed1983

Effects of interferon-alpha on cytomegalovirus reactivation syndromes in renal-transplant recipients.

We have previously demonstrated that six weeks of prophylaxis with interferon-alpha delays cytomegalovirus excretion and decreases viremia in recipients of kidney transplants. In a double-blind trial to evaluate the effects of a longer course of prophylaxis, we gave either 3 X 10(6) units of interferon or placebo intramuscularly to 42 patients before transplant surgery was performed. After surgery, doses were given three times a week for six weeks and then twice a week for eight weeks (total of 102 X 10(6) units). Clinical signs of cytomegalovirus infection were markedly reduced in interferon recipients. These signs developed in 7 of 22 placebo recipients and 1 of 20 interferon recipients (P = 0.03). Opportunistic superinfections (Aspergillus fumigatus and Pneumocystis carinii) occurred only in patients given placebo. Cytomegalovirus-associated glomerulopathy developed in one interferon recipient and three placebo recipients. Survival of patients and grafts was equivalent in both treatment groups, and minimal toxicity was observed with interferon. In seropositive renal-transplant recipients, interferon-alpha affords effective prophylaxis against serious cytomegalovirus infections.

Adult↗
PubMed1983

Association of herpesvirus infections with T-lymphocyte-subset alterations, glomerulopathy, and opportunistic infections after renal transplantation.

We studied the interrelation among herpes-virus infections, T-lymphocyte subsets, opportunistic infections, and renal histopathology in 28 recipients of renal allografts. All primary or reactivated herpesvirus infections occurring in the first three months after transplantation in recipients of cadaveric grafts accompanied persistent inversions in the ratio of OKT4 (helper/inducer) to OKT8 (cytotoxic/suppressor) lymphocytes. In the less heavily immunosuppressed recipients of organs of living related donors, these inversions were seen only in association with clinically apparent cytomegalovirus infections. Five of seven opportunistic infections occurred in patients with OKT4/OKT8 ratios of less than 1.0. Biopsy specimens from patients with renal dysfunction occurring in association with a low OKT4/OKT8 ratio frequently revealed glomerular damage rather than acute cellular rejection. Monitoring of T-lymphocyte subsets provides early evidence of herpesvirus infections and identifies patients at increased risk for opportunistic infection after renal transplantation.

Biopsy↗
PubMed1983

Immunological monitoring of diabetic and nondiabetic recipients of renal allografts.

Peripheral blood T-lymphocyte populations were monitored sequentially in diabetic recipients of renal allografts. Unfractionated buffy coat preparations were reacted with the murine monoclonal antibodies, OKT3 (all circulating T-cells), OKT4 (helper/inducer/regulatory T-cells), and OKT8 (cytotoxic/suppressor cells). Levels of peripheral blood lymphocyte subpopulations of diabetic patients monitored prior to transplantation revealed no significant abnormalities. Following transplantation, but prior to any therapy for acute rejection, the mean percentage of OKT3, 4, and 8 reactive cells in diabetic recipients closely resembled those observed in nondiabetic recipients. After treatment for acute rejection, a marked decrease in the mean OKT4/OKT8 ratio from normal (1.90 +/- 0.7) was observed in both diabetic (1.04 +/- 0.5), and nondiabetic (1.35 +/- 0.5) allograft recipients. Eleven of thirteen diabetic recipients with long-term functioning allografts were found to have a depressed OKT4/OKT8 ratio (mean 1.03 +/- 0.6). T-cell subset monitoring of diabetics with end-stage renal failure failed to reveal any significant differences from nondiabetic, uremic patients. The high incidence (75%) of allograft rejection noted in these diabetic allograft recipients similarly suggests normal immunocompetence. Following successful completion of rejection therapy, however, reduction in the ratio of OKT4 to OKT8 reactive cells suggests that an alteration in immune responsiveness has occurred. Immunological monitoring of these long-term diabetic recipients with functioning allografts suggests that the observation of a consistently depressed OKT4/OKT8 ratio may (1) be useful in predicting continued allograft function and (2) prompt the more rapid reduction of steroid medication to maintenance dosage since this pattern may be indicative of subclinical viral infection.

Adult↗
PubMed1983

New approaches to donor crossmatching and successful transplantation of highly sensitized patients.

A class I HLA molecule may bear not only a private or unique determinant, but a shared, yet discrete, public epitope. These public determinants occur with a much higher frequency in the random donor population than the associated private determinants--and thus, are encountered more often in random donor blood transfusions and in renal transplantation. Sera from highly sensitized dialysis patients have been reported to contain a restricted number of antibodies to public determinants rather than a diverse array of antibodies directed against the private HLA-AB epitopes. As detailed in this report, comprehensive serum analysis of the public antibodies in highly sensitized transplant candidates has optimized identification of potential crossmatch-compatible donors and has avoided needless crossmatches. During the past two years, the incidence of renal transplantation from cadaveric donors to highly sensitized recipients has doubled at this institution. At 10-25 months following transplantation, 70% of these allografts are functioning. Private HLA class I antigen incompatibility was not a barometer for exclusion in the final donor crossmatch of these highly sensitized recipients. Furthermore, positive donor T cell crossmatches with sera obtained more than six months prior to transplantation may not represent an impediment to successful transplantation. We conclude that the approach of detailed antibody analysis can result in an improved outlook for successful transplantation of more dialysis patients who are highly sensitized to the class I HLA alloantigens.

Antibodies↗
PubMed1983

Monitoring immunosuppression following renal transplantation.

Renal allograft recipients were given azathioprine and prednisone for immunosuppression following transplantation. In addition, pulses of steroids or courses of treatment with antithymocyte globulin (ATG) or PAN.OKT3 were employed to combat acute rejection episodes. Our results support the concept that ATG and PAN.OKT3 are useful in the treatment of acute kidney allograft rejection. In our experience, ATG often reversed acute kidney allograft rejection episodes and then provided relatively long-lasting immunosuppression with stable graft function. In contrast, PAN.OKT3 was more effective in reversing acute rejection, but subsequent rejection episodes occurred more frequently. In patients treated with PAN.OKT3, cells reacting with OKT3, OKT4 and OKT8 were removed from the circulation within minutes following the initial treatment, and the levels of these cells remained dramatically depressed during the first few days of treatment. Subsequently, peripheral blood cells which reacted with OKT4 or OKT8, but not OKT3, could be detected in most patients, even though treatment continued and excess circulating PAN.-OKT3 was present. Experiments in which these cells were cultured for 24 or 72 hr indicated that antigenic modulation by OKT3 had occurred in vivo. These results raise interesting questions about the mode of action of PAN.OKT3, and suggest that the combination of PAN.OKT3 with an agent which can establish long-lasting immunosuppression may be more effective than either agent given alone.

Antibodies, Monoclonal↗
PubMed1982

Experience with pyeloureterostomy in renal transplantation.

Pyeloureterostomy was used as the preferred method of urinary tract reconstruction in 260 of 371 consecutive renal allograft procedures performed between September 1967 and December 1980. Initially chromic catgut suture was used for the anastomosis in 96 patients with ten complications developing (10.4%). Because of the high incidence of anastomotic leakage (8.3%) with chromic catgut suture, the next 101 pyeloureterostomies were constructed using 7-0 Tevdek. Although urinary leakage occurred in only five of these patients (4.9%), late stone formation occurred along the suture material in three patients (2.9%), influencing the conversion to 7-0 Prolene for this anastomosis. With this suture material, only two complications have occurred in 63 subsequent pyeloureterostomies (3.1%), neither related to the anastomosis. In comparison, eight complications developed in 111 patients who underwent reconstruction with the Politano-Leadbetter method of ureteroneocystostomy (7.2%). The currently recommended method for pyeloureterostomy, as described, when combined with meticulous attention to technical details has made pyeloureterostomy a safe and effective method of urinary tract reconstruction in renal transplant recipients, with morbidity indistinguishable from that of ureteroneocystostomy.

Humans↗
PubMed1982

Monoclonal antibodies to human T cell subsets: use for immunological monitoring and immunosuppression in renal transplantation.

Sequential monitoring of peripheral blood T cell populations was performed in normal control individuals and in 55 renal allograft recipients. In addition, 66 patients exhibiting prolonged renal allograft survival were each evaluated at least once with the same monoclonal antibodies. A normal or elevated OKT4:OKT8 ratio, especially in the presence of rising numbers of OKT4+ cells was predictive of possible future graft rejection. This observation, when followed by rising serum creatinine values coupled with biopsy evidence of glomerulopathy, was found in at least 15% of graft recipients. In a small number of patients, graft rejection episodes were successfully suppressed by administration of therapeutic doses of OKT3 antibody. However, production of anti-OKT3 antibodies was observed and may be expected to limit administration of this agent to a single short course in each patient.

Acute Disease↗
PubMed1981

Use of monoclonal antibodies to T-cell subsets for immunologic monitoring and treatment in recipients of renal allografts.

Using monoclonal antibodies and flow cytometry, wer serially monitored lymphocyte subpopulations in renal-allograft recipients treated with either conventional immunosuppression or a monoclonal antibody. In 29 patients given conventional suppression, highly significant correlations between changes in T-cell subsets and rejection were noted. Normal or elevated ratios of OKT4 (helper/inducer) to OKT8 (suppressor/cytotoxic) cells were associated with rejection unless the donor was HLA identical or the total number of T cells was extremely low. In patients with low ratios, rejection seldom occurred. Two patients treated with OKT3 monoclonal antibody for acute rejection had rapid disappearance of OKT3-reactive cells from the peripheral blood and prompt reversal of rejection. The use of monoclonal antibodies allows the precise determination of changes in T-cell subsets and promises the development of therapeutic protocols that can be designed to manipulate selected lymphocyte populations.

Antibodies↗
PubMed1981

Treatment of acute renal allograft rejection with OKT3 monoclonal antibody.

Eight cadaver donor renal allograft recipients, who had received azathioprine and prednisone from the day of transplantation, were treated with OKT3 monoclonal antibody (reactive with all mature peripheral blood T cells) at the time of diagnosis of acute rejection. In all cases, loss of essentially all detectable peripheral blood OKT3-reactive cells was noted within minutes after the initial 1- to 5-mg i.v. infusion. Chills and fever invariably occurred following the first or second infusion of monoclonal antibody, but were not noted during the subsequent, 10- to 20-day course of therapy, suggesting rapid cell lysis as the etiology of this toxicity. The established rejection episode was reversed in all cases within 2 to 7 days without addition of any therapy other than OKT3 antibody and despite continued lowering of the steroid dosages. During the subsequent 3- to 12-month follow-up period, further rejection episodes occurred in five of these patients, two of these were irreversible with conventional therapy so that six of the eight allografts continue with excellent renal function. These preliminary observations suggest that homogeneity, limited dosage requirements, and ease of in vitro monitoring of dosage effects should markedly simplify the use of monoclonal antibody to T cell populations in human allograft recipients. This second generation of antilymphocyte preparations offers the potential for not only increased effectiveness but also the possibility of manipulating specific T cell subsets.

Antibodies, Monoclonal↗
PubMed1981

Temporary skin transplantation for the treatment of extensive burns.

Survival of the extensively burned patient depends upon rapid excision of necrotic tissue, and skin grafting to obtain wound closure. When a sufficient supply of autogenous skin is not available to provide wound coverage, allograft skin has been successfully substituted. Although burn patients have been noted to be immunologically hyporesponsive, their immune response to skin allografts has necessitated the administration of immunosuppressive therapy, to assure the retention of the allografts until sufficient autogenous skin can be utilized. The temporary transplantation of skin allografts has proved successful in the treatment of extensively burned children.

Antilymphocyte Serum↗
PubMed1978

Impact of blood transfusion on renal transplantation.

The relationship between transfusion of different preparations of blood, sensitization to HLA antigens and survival of subsequent kidney transplants was investigated in 90 consecutive recipients. HLA lymphocytotoxins in transplant candidates precluded or greatly delayed receipt of an allograft (p less than 0.0005). Furthermore, only 17% of such sensitized recipients had functioning grafts one year after transplantation compared to 57% survival for nonsensitized recipients (p less than .02). A small number of nonsensitized patients who were never transfused had surprisingly poor one year graft survival (25%). If frozen blood is used for transfusion rather than whole/packed RBC, the incidence of patient sensitization can be markedly reduced without subsequent compromise in transplant survival (51%). It is concluded that as a consequence of avoiding HLA sensitization by transfusion of frozen blood (processed by agglomeration), the period of hemodialysis required for potential graft recipients will be shortened and an increased proportion of potential recipients will be successfully treated by transplantation.

Blood Transfusion↗