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Biomedical subjects

R H Kerman

Publications and source records attributed to R H Kerman.

At least 109 records · Page 6Linked to original sources

The influence on pretransplant blood transfusions from random donors on immune parameters affecting cadaveric allograft survival.

The number of pretransplant blood transfusions (BT) from random donors influences the recipient's immune response status and suppressor cell number and function, as well as allograft survival. The 54% one-year survival rate for 104 cadaveric renal allograft recipients treated with azathioprine and prednisone was divisible into two groups: 74.5% in 51 patients receiving greater than 5 BT and 34% for 53 patients with less than 5 BT (P less than 0.02). Transfusions enhanced the benefit of HLA A, B, and DR compatibility on graft survival: 33 recipients of well-matched grafts (less than 2 A, B, and 0-1 DR mismatches) had a one-year survival rate of 94% when pretreated with greater than 5 BT, compared with 38% when receiving less than 5 BT (P less than 0.05). The graft survival of 73% (36/49) displayed by patients determined preoperatively to be weak immune responders was significantly better than the 36% survival (20/55) demonstrated by strong immune responders (P less than 0.01). The transfusion history correlated with immune responder status: 76% (39/51) of patients receiving greater than 5 BT were weak immune responders, whereas 81% (43/53) of patients receiving less than 5 BT were strong immune responders (P less than 0.001). Ninety-two percent (12/13) of patients with greater than 5 BT, but only 58% (10/17) of patients with less than 5 BT, had a normal number of OKT8+ T suppressor cells. Only 1 X 10(5) mononuclear cells from patients with greater than 5 BT rather than 4 X 10(5) cells from patients with less than 5 BT caused 50% suppression of a third-party MLC. Thus, patients receiving greater than 5 BT are more likely to display weak immune responses, normal numbers of OKT8 cells, strong suppressor function in vitro, and prolonged allograft survival.

Antibodies, Monoclonal↗

Suppression of mixed leukocyte culture using leukocytes from normal individuals, uremic patients, and allograft recipients.

The suppressor cell function of peripheral blood mononuclear leukocytes (MNLs) from normal individuals, renal failure patients, and allograft recipients was evaluated using a suppressor cell assay wherein putative suppressors were added at the initiation of a third-party, one-way mixed leukocyte culture (MLC). MNLs from renal allograft recipients displayed the greatest suppressive activity (P less than 0.05): 50% suppression was achieved with 0.5 x 10(5) MNLs from allograft recipients, 2 x 10(5) MNLs from end stage renal disease patients, or 4 x 10(5) MNLs from normal individuals. The frequency of tests displaying positive MLC suppression using 1 x 10(5) MNLs was 90% (383 of 426) for allograft recipients compared with 60% (83 of 138) for renal failure patients and 28.2% (29 of 103) for normal individuals (P less than 0.01). The suppression displayed by 1 x 10(5) MNLs from potential allograft recipients receiving more than five pretransplant blood transfusions (BTs) was equal to that of 4 x 10(5) MNLS from patients receiving less than five BTs (P less than 0.05). Moreover, the frequency of positive MLC suppression from patients treated with more than five versus less than five BTs was 80% versus 40% (P less than 0.001). Although suppression of MLC appeared to be mainly dependent on an esterase (+)-adherent cell, there was no significant difference between the percentage of esterase (+) cells in unfractionated MNLs from the three groups of individuals, suggesting that MLC suppression was attributable to the functional performance rather than the number of suppressor MNLs. Preliminary data suggest a relationship between the level of MLC suppressive activity detected pretransplant and the outcome of the allograft at 6 months.

Blood Transfusion↗

Serial measurement of nonspecific immune parameters in chronically hemodialyzed renal failure patients.

Nonspecific immune monitoring of the percentage active T (A-T) rosette-forming cells (RFC) and spontaneous blastogenesis (SB) appear to be useful indexes of host reaction toward allografts. In order to assess the significance of the observed changes, renal failure patients were serially evaluated before and after hemodialysis for the percentage of total T (T-T) and A-T RFC and for peripheral blood leukocyte metabolic activity measured by a whole blood spontaneous blastogenesis (SB) assay. Renal failure patients had a significantly lower (P less than 0.05) percentage of T-T RFC than normal persons, while the percentage A-T RFC and SB remained stable. A hemodialysis treatment did not change the mean values of any of the three parameters. On the other hand, serial patient evaluation over 3 months revealed significant fluctuations in the percentage T-T RFC, but not the percentage A-T RFC and SB. Since the percentage A-T RFC and SB are relatively constant measures of immune status in ungrafted patients, significant changes in these nonspecific immune probes may reflect allograft rejection.

Female↗

Correlation of nonspecific immune monitoring with rejection or impaired function of renal allografts.

Two nonspecific immunological assays were combined with radionuclide scanning to monitor 113 patients thrice weekly following allotransplantation. The nonspecific immune assays included measurement of the percentage of active T rosette-forming cells (% A-T RFCs) and spontaneous blastogenesis (SB). An increase in SB and decrease in % A-T RFCs (greater than 1 sd of normal controls) constituted an immune event. The immune parameters were correlated with thrice weekly radionuclide studies which were computer analyzed for glomerular and tubular function. Alteration of the immunological and radionuclide parameters significantly correlated (P less than 0.001) with 90 rejection episodes displayed by 72 nonantithymocyte globulin (ATG)-treated renal allograft recipients during the first 30 postoperative days. In the absence of clinically defined rejection, changes in immune parameters correlated with (1) decline of radionuclide parameters and (2) alterations in weight, temperature, creatinine clearance, and serum creatinine, suggesting subclinical events. As a result of the effects of ATG on lymphocytes, a similar comparison could not be made for 41 other patients treated with this immunosuppressive drug. The incidence of false positive tests was 12.7%. Thus, the combination of two nonspecific immune parameters, % A-T RFCs and SB, with computerized analysis of radionuclide scans may afford a reliable index to diagnose early rejection or impaired function of renal allografts.

Diagnosis, Differential↗

Improved allograft survival of strong immune responder-high risk recipients with adjuvant antithymocyte globulin therapy.

The pretransplant cellular immune responsiveness of 90 renal failure patients was correlated with subsequent allograft survival. Patients were subdivided in two bases: whether the pretransplant immune parameter values were above (strong responder) or below (weak responder) the group median, and whether they were responsive or anergic to recall skin test antigens. In a group of 72 cadaveric renal allograft recipients, treated with only Imuran and prednisone, the overall 1-year graft survival was 48%. Pretransplant immunocompetence correlated with graft survival: factors predicting longer allograft survival (P < 0.01) included: percentage of active T rosette-forming cells (A-T RFCs) < 36.5%, anergy to microbial skin test (ST) antigens, in vitro spontaneous blastogenesis (SB) < 14,600 cpm, and response to a panel of five donors in mixed lymphocyte culture (PMLC) < 28,000 cpm. In the two groups, weak and strong responders, the 1-year graft survival rates differed: 63% versus 32% when segregated by the A-T RFC parameter, 63% versus 33% for ST, 57% versus 36% for SB, and 63% versus 35% for PMLC. There were no significant differences in the number of HLA mismatches between the two groups. An additional group of 18 patients was treated with adjuvant immunosuppressive therapy by prophylactic administration of antithymocyte globulin (ATG; Upjohn Co.). Strong, but not weak, responders treated with ATG displayed a significantly improved (P < 0.01) 1-year graft survival over that of the untreated group. Thus, pretransplant immunological assessment may guide the selection of adjuvant immunosuppressive therapy to improve renal allograft survival in strong immune responders at high risk of rejection.

Antilymphocyte Serum↗