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Biomedical subjects

C F Shield

Publications and source records attributed to C F Shield.

At least 73 records · Page 4Linked to original sources
PubMed1989

The reuse of OKT3 after previous rejection or induction therapy in cadaveric renal transplantation.

Twenty-three patients were retreated once and two patients were retreated two times with OKT3 after previous rejection or induction therapy in cadaveric renal transplantation. Retreatment was effective when the initial treatment was for rejection therapy or induction therapy protocols. Rejection reversal was 83% in the rejection group and 90% in the induction group. Long-term allograft function was 42% in the rejection group and 78% in the induction group. It is speculated that the immune response is more adequately controlled in the induction group. The antibody responses to retreatment were no antibody production (n = 9), antibody production on retreatment (n = 2), no change in antibody titer (n = 4), and increase in previously identified antibody titer (n = 3). Two patients with high titered antibodies had treatment failures caused by preformed antimouse antibodies. The only changes in antibody specificity occurred in patients with a change in preformed antibody. Retreatment of allograft rejection in patients previously treated with OKT3 has again been demonstrated to be effective. It is suggested that retreatment after OKT3 induction therapy may be the most effective.

Antibodies, Monoclonal↗
PubMed1988

Recurrence of acute rejection in the absence of CD3-positive lymphocytes.

Allograft rejection is the single largest impediment to successful transplantation. Therapy targeted to lymphocytes has been in practice for many years using polyclonal heteroantisera. These products are generally accepted as being useful for the prevention and treatment of rejection; however, there have been problems with specificity, lot to lot variability, and supply. Therapy with monoclonal antibodies such as OKT3 may circumvent these problems and may allow for refined specificity. OKT3 has been shown to be highly effective at reversing acute renal allograft rejection. The few treatment failures were attributed to anti-mouse antibodies eliminating the OKT3, or to delay of therapy to such a late stage that rejection was irreversible. We present two cases which demonstrate successful reversal of acute rejection in cadaveric renal transplants by OKT3. The reversal was transient, however, in both cases, as both patients experienced recurrence of rejection while still receiving the monoclonal antibody. This occurred despite the absence of CD3-positive cells in the peripheral blood, and the presence of excess OKT3 in the serum. This implies that CD3-negative lymphocytes may under certain circumstances contribute to the rejection phenomenon.

Adult↗
PubMed1988

Early use of OKT3 monoclonal antibody in renal transplantation to prevent rejection.

OKT3 monoclonal anti-T cell antibody was used during the first 2 weeks following cadaveric renal transplantation to prevent rejection. When compared with a control group receiving triple immunosuppression with cyclosporine, azathioprine, and prednisone, the OKT3, azathioprine, and prednisone group had significantly fewer acute rejections during the first month (6% v 50%; P less than 0.01), and the mean time of onset of the first rejection was significantly delayed (day 47 v day 8; P less than 0.01) in the OKT3 prophylaxis group. OKT3 was administered intraoperatively safely and without complications on the day of transplantation. The well-reported first dose reaction to OKT3 was similar in these patients when compared with patients receiving OKT3 for treatment of rejection. Anti-OKT3 antibody development occurred in half of the patients receiving OKT3, and did not prevent the subsequent use of OKT3 in these patients, whose rejections following OKT3 prophylaxis were steroid reversible. There were no deaths among the patients receiving prophylactic OKT3, and during a 15-month follow-up, only three of 34 kidneys were lost for any reason. In addition to its use for primary and steroid-resistant rejection, OKT3 may be useful early after transplantation to prevent rejection.

Antibodies, Anti-Idiotypic↗
PubMed1988

Immunologic monitoring during and after OKT3 therapy.

Immunologic monitoring should be undertaken during and for 6 weeks after OKT3 treatment. CD3 absolute cell determinations should be obtained three times per week during therapy. A progressive increase of the absolute CD3 cell count above 10/microL is suggestive of an inadequate OKT3 serum level, most often due to an early antimurine response. Weekly posttherapy antimurine response should be determined. The presence or absence of an antimurine response can be suggestive of a successful response to a second therapeutic course of OKT3.

Adult↗
PubMed1988

Successful transplantation of blood group A2 kidneys into non-A recipients.

The ABO subgroup A2 has been reported to be less reactive with the anti-A1 antibody naturally occurring in the serum of group O and B recipients and to occur in approximately 20% of group A individuals. Between March 1986 and February 1987, the Midwest Organ Bank (MOB) in Kansas City, screened all group A renal donors for the A2 subgroup. A total of 190 cadaverdonor kidneys were retrieved during this time, of which 68 were subgroup A1 and 16 were subgroup A2 (incidence of A2 = 19% of As and 8.5% of all donors). Of the subgroup A2 kidneys, 13 were transplanted into 9 group O and 4 group B recipients. One group O recipient received an HLA-identical A2 living-related graft. Recipients were not preselected or modified by splenectomy, plasmapheresis, or other means, and were treated with cyclosporine, steroids--and, in most cases, azathioprine, after transplantation. There was one hyperacute rejection and there were 5 acute cellular rejection episodes, 3 of which were reversed. One additional patient died at 2.5 months with a functioning graft. Including the successful living-related graft, 10 of 14 patients (71%) have functioning grafts, with a follow-up of 5 to 14 months, and a mean creatinine of 1.7 mg/dl. We find that the A2 subgroup represents a small but important minority of A donors, and that transplantation into non-A recipients can generally, but not universally, be safely accomplished. We recommend the screening of A donors for the A2 subgroup in both the cadaver-donor and living-related groups, and suggest that the utilization of A2 donors in non-A patients may contribute to the transplantation of group O and highly sensitized patients--and, in some cases, improve the degree of HLA matching.

ABO Blood-Group System↗
PubMed1988

Effectiveness of a second course of OKT3 monoclonal anti-T cell antibody for treatment of renal allograft rejection.

A second course of OKT3 monoclonal anti-T cell antibody was given to 21 recipients of kidney transplants. Rejections reversed in 43% of patients in whom 95% of rejections had reversed with their initial OKT3 course. Reversal was highly dependent upon the timing of rejection, anti-OKT3 antibody production, and T cell CD3 modulation. Rejections treated greater than 90 days after transplantation were resistant to OKT3 reversal. High-titer anti-OKT3 antibodies prevented OKT3 reversal of rejection, and effective CD3 (the cell surface target of OKT3) modulation was necessary for successful OKT3 reversal of rejection. Reexposure to OKT3 further stimulated anti-OKT3 antibody production and broadened the specificity of the antibodies produced. OKT3 can effectively and safely be used a second time for treatment of early T cell-mediated renal allograft rejections if high-titer anti-OKT3 antibodies have not been made.

Adolescent↗
PubMed1987

Therapeutic use of OKT3 monoclonal antibody for acute renal allograft rejection.

OKT3, a murine monoclonal anti-T-cell antibody, was used to treat acute renal allograft rejection crises in 140 patients. When used for primary treatment of initial rejections, it was effective in all 20 recipients of related-donor (RD) grafts and in 70 of 74 recipients of cadaver-donor (CD) grafts. OKT3 was also used for resistant rejection unresponsive to conventional antirejection drugs and was effective in 11 of 13 RD and in 26 of 33 CD recipients. Rerejection occurred in 58% of patients in the OKT3 primary treatment group and in 35% of patients in the OKT3 rescue group. Fifty-nine percent of the patients produced anti-OKT3 antibodies. Nearly all recipients experienced a flu-like syndrome following the first and second daily doses of OKT3. Two-year actuarial patient survivals were 100 and 96% for RD and CD recipients, respectively. In the OKT3 primary treatment group, two-year actuarial RD and CD graft survivals were 91 and 76%, respectively. In the OKT3 rescue group, the two-year actuarial RD and CD graft survivals were 85 and 55%, respectively. A proposed immunosuppressive effect of OKT3 is T-cell inactivation by blocking antigen receptors linked to OKT3-reactive molecules. Reuse of OKT3 for recurrent rejection or subsequent organs may be hampered by anti-OKT3 antibody production. OKT3 is an effective steroid-sparing treatment for renal allograft rejection.

Antibodies, Anti-Idiotypic↗
PubMed1987

Comparison of antimouse and antihorse antibody production during the treatment of allograft rejection with OKT3 or antithymocyte globulin.

Antimouse antibody is produced from 40 to 68% of the time after administration of Orthoclone OKT3. In patients treated with OKT3, however, if the concomitant immunosuppression is not decreased, the incidence of the antibody production is reduced to 40%. Similarly, 33% of patients developed antihorse antibody after the initial antithymocyte globulin (ATG) administration. Most of the time, the antibody production is low-titered for both OKT3 and ATG.

Animals↗
PubMed1986

OKT3 monoclonal antibody plasma levels during therapy and the subsequent development of host antibodies to OKT3.

OKT3 levels and the presence of human antibodies to OKT3 were determined in the plasma of 66 patients receiving OKT3 monoclonal antibody (5 mg i.v. daily) for the treatment of acute renal allograft rejection. Plasma 24-hr trough levels of OKT3 rose over the first three days and then remained in a steady state over the remainder of the 14-day period of OKT3 therapy, with a mean level of 902 +/- 71 ng/ml (mean + SEM). On termination of OKT3 therapy plasma levels of OKT3 dropped to very low levels after 3 days. Host antibodies, usually of low titer, developed in a number of patients, usually 2-3 weeks after the start of OKT3 therapy. 37/43 patients (86%) who received OKT3 alone developed IgG anti-OKT3 antibodies; 9/23 patients (39%) who received Cytoxan in addition to OKT3 developed IgG anti-OKT3 antibodies, a significantly lower (P = 0.0002) incidence. The present regimens permitted maintenance of adequate levels of circulating OKT3 for 2 weeks, a sufficient time to reverse acute renal allograft rejection in most patients.

Antibodies, Anti-Idiotypic↗
PubMed1986

The association of antivascular endothelial cell antibody with hyperacute rejection: a case report.

Early graft loss almost always occurs when recipients of a renal allograft develop antibody directed against antigens specific for donor vascular endothelial cells (VECs) and peripheral blood monocytes. In studies involving recipients of human leukocyte antigen identical, living-related grafts exhibiting preformed antibody to the VEC antigens of their donors, the median onset of rejection was 3 days after transplantation. Although preformed antibody to VEC antigens has been related in numerous articles to early graft loss, there has never been a published report of anti-VEC antibody leading to hyperacute rejection. We report a patient who hyperacutely rejected a renal allograft after undergoing a donor-specific transfusion protocol with her mother in which the kidney was removed in less than 24 hours. Nine months later the patient had a retransplantation with an allograft from a cadaveric donor. The cadaveric graft was again hyperacutely rejected, and this kidney was removed immediately. Anti-VEC/monocyte antibody directed against both donors was detected in the patient's pretransplant sera. With the exception of a positive B-lymphocyte crossmatch with her mother, all the standard crossmatches were negative.

Adolescent↗
PubMed1985

Renal transplant perfusion during aortoiliac aneurysmectomy.

Aortic surgery in recipients of renal transplants requires a method of maintaining intraoperative graft perfusion. A case is presented in which a temporary shunt from the suprarenal aorta to the ipsilateral common femoral artery was used to perfuse a renal transplant during aortoiliac aneurysmectomy. Other methods of renal graft perfusion are discussed.

Aneurysm↗
PubMed1984

Acute diverticulitis. Comparison of treatment in immunocompromised and nonimmunocompromised patients.

The clinical course and required treatment of diverticulitis were reviewed in 76 nonimmunocompromised patients and 10 immunocompromised patients. The immunocompromised patients presented with either minimal or no symptoms and findings. Therefore, to make the diagnosis of acute diverticulitis in this group, a high index of suspicion must be maintained. The required treatment varied considerably between the two groups. In 45 nonimmunocompromised patients (76 percent), medical therapy was successful. Medical treatment failed in the other 14 patients (24 percent). However, the compromised group had no patients in whom medical therapy was successful (100 percent failure rate). Thirty-one of the nonimmunocompromised patients (41 percent) required an operation, whereas 100 percent of the immunocompromised patients with acute diverticulitis required an operation. By relating postoperative complications, we were unable to determine the initial operative procedure of choice in the nonimmunocompromised group; however, in the immunocompromised group, colostomy and resection had fewer surgical complications than colostomy and drainage. The immunocompromised patient with acute diverticulitis requires operation. We believe the operation of choice is colostomy and resection of the involved segment.

Acute Disease↗