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15. Safety and efficacy of granulocyte colony-stimulating factor in kidney and liver transplant recipients

Author

Turgeon, N., Hovingh, G. K., Fishman, J. A., Basgoz, N., Tolkoff-Rubin, N. E., Doran, M., Cosimi, A. B., Rubin, R. H., and Other departments

Abstract

Leukopenia is not infrequently encountered following solid organ transplantation, most often in the setting of cytomegalovirus (CMV) disease and/or its treatment with ganciclovir. The present study was undertaken to determine the safety and efficacy of granulocyte colony-stimulating factor (G-CSF) in renal and liver transplant recipients with leukopenia. Between 1 June 1991 and 1 June 1998, patients received G-CSF for 2 indications: 1) white blood cell count (WBC)

Published
2000

16. INCREASED FREQUENCY OF REGULATORY T CELLS IN PATIENTS RECEIVING HLA HAPLOIDENTICAL COMBINED KIDNEY AND BONE MARROW TRANSPLANTATION TO INDUCE TOLERANCE

Author

Morokata, T., primary, LoCascio, S. A., additional, Preffer, F. I., additional, Dombkowski, D. M., additional, Andreola, G., additional, Crisalli, K., additional, Kawai, T., additional, Saidman, S., additional, Spitzer, T., additional, Tolkoff-Rubin, N., additional, Cosimi, B., additional, Sachs, D. H., additional, and Sykes, M., additional

Published
2010
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17. TRANSIENT MIXED CHIMERISM, LYMPHOCYTE RECOVERY AND EVIDENCE FOR EARLY DONOR-SPECIFIC UNRESPONSIVENESS IN PATIENTS RECEIVING COMBINED KIDNEY AND BONE MARROW TRANSPLANTATION TO INDUCE TOLERANCE

Author

LoCascio, S. A., primary, Morokata, T., additional, Chittenden, M., additional, Preffer, F. I., additional, Dombkowski, D. M., additional, Andreola, G., additional, Crisalli, K., additional, Kawai, T., additional, Saidman, S., additional, Spitzer, T., additional, Tolkoff-Rubin, N., additional, Cosimi, B., additional, Sachs, D. H., additional, and Sykes, M., additional

Published
2010
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21. ALLORESPONSES IN TOLERANT RECIPIENTS OF COMBINED KIDNEY/BONE MARROW TRANSPLANTATION WITH NON-MYELOABLATIVE CONDITIONING

Author

Fudaba, Y, primary, Shaffer, J M., additional, Kraus, A, additional, Cosimi, A B., additional, Delmonico, F L., additional, Dey, B, additional, Kawai, T, additional, McAfee, S, additional, Preffer, F, additional, Tolkoff-Rubin, N, additional, Sachs, D H., additional, Saidman, S L., additional, Spitzer, T R., additional, and Sykes, M, additional

Published
2004
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22. MECHANISMS OF DONOR-SPECIFIC UNRESPONSIVENESS IN TOLERANT RECIPIENTS OF COMBINED NON-MYELOABLATIVE HLA-MISMATCHED BONE MARROW AND KIDNEY TRANSPLANTATION

Author

Shaffer, J, primary, Kawai, T, additional, Cosimi, A B., additional, Fudaba, Y, additional, Saidman, S, additional, Preffer, F, additional, Dombkowski, D, additional, Delmonico, F, additional, McAfee, S, additional, Tolkoff-Rubin, N, additional, Ballen, K, additional, Dey, B, additional, Spitzer, T R., additional, Sachs, D H., additional, and Sykes, M, additional

Published
2004
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23. COMBINED KIDNEY AND BONE MARROW TRANSPLANTATION FOR INDUCTION OF MIXED CHIMERISM AND RENAL ALLOGRAFT TOLERANCE IN HLA MISMATCHED TRANSPLANTATION

Author

Kawai, T, primary, Sachs, D H., additional, Spitzer, T, additional, Sykes, M, additional, Tolkoff-Rubin, N, additional, Delmonico, F, additional, Saidman, S, additional, Shaffer, J, additional, Dey, B, additional, McAfee, S, additional, Ko, D, additional, Wong, W, additional, Williams, W, additional, Goes, N, additional, Hertl, M, additional, Smith, R N., additional, Colvin, R B., additional, and Cosimi, A B., additional

Published
2004
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41. Epstein-Barr virus infection in renal transplant recipients. Effects of antithymocyte globulin and interferon.

Author

Cheeseman, Sarah H., Henle, Werner, Rubin, Robert H., Tolkoff-Rubin, Nina E., Cosimi, Benedict, Cantell, Kari, Winkle, Susan, Herrin, John T., Black, Paul H., Russell, Paul S., Hirsch, Martin S., Cheeseman, S H, Henle, W, Rubin, R H, Tolkoff-Rubin, N E, Cosimi, B, Cantell, K, Winkle, S, Herrin, J T, and Black, P H

Subjects
GLOBULINS, INTERFERONS, EPSTEIN-Barr virus, KIDNEY transplantation, THERAPEUTIC use of interferons, ANTILYMPHOCYTIC serum, CLINICAL trials, COMPARATIVE studies, DEAD, HOMOGRAFTS, IMMUNOSUPPRESSION, RESEARCH methodology, MEDICAL cooperation, PLACEBOS, RESEARCH, T cells, VIRAL antibodies, EVALUATION research, RANDOMIZED controlled trials, VIREMIA, THERAPEUTICS
Abstract

We studied Epstein-Barr (EB) virus excretion and antibody in 41 renal transplant recipients enrolled in a placebo-controlled trial of human leukocyte interferon. Half the patients were also treated with antithymocyte globulin. Epstein-Barr virus excretion occurred more often in recipients of cadaver kidneys (P = 0.03) and those receiving antithymocyte globulin (P = 0.04) and less often in patients given interferon (P = 0.08). Antibody to viral capsid antigen increased fourfold or more in 12 of 22 patients treated with antithymocyte globulin and in none of the non-antithymocyte globulin-treated group (P = 0.0002). Antibody to the restricted component of early antigen rose fourfold or more in eight patients and appeared related to the occurrence of syndromes similar to those attributed to cytomegalovirus in transplant recipients. We conclude that increasing immunosuppression augments the rate of EB virus reactivation and that EB virus may be an important pathogen in heretofore ill-defined syndromes. [ABSTRACT FROM AUTHOR]

Published
1980
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44. Myeloma Responses and Tolerance Following Combined Kidney and Nonmyeloablative Marrow Transplantation: In Vivoand In VitroAnalyses

Author

Fudaba, Y., Spitzer, T.R., Shaffer, J., Kawai, T., Fehr, T., Delmonico, F., Preffer, F., Tolkoff-Rubin, N., Dey, B.R., Saidman, S.L., Kraus, A., Bonnefoix, T., McAfee, S., Power, K., Kattleman, K., Colvin, R.B., Sachs, D.H., Cosimi, A.B., and Sykes, M.

Abstract

Six patients with renal failure due to multiple myeloma (MM) received simultaneous kidney and bone marrow transplantation (BMT) from HLA-identical sibling donors following nonmyeloablative conditioning, including cyclophosphamide (CP), peritransplant antithymocyte globulin and thymic irradiation. Cyclosporine (CyA) was given for approximately 2 months posttransplant, followed by donor leukocyte infusions. All six patients accepted their kidney grafts long-term. Three patients lost detectable chimerism but accepted their kidney grafts off immunosuppression for 1.3 to >7 years. One such patient had strong antidonor cytotoxic T lymphocyte (CTL) responses in association with marrow rejection. Two patients achieved full donor chimerism, but resumed immunosuppression to treat graft-versus-host disease. Only one patient experienced rejection following CyA withdrawal. He responded to immunosuppression, which was later successfully withdrawn. The rejection episode was associated with antidonor Th reactivity. Patients showed CTL unresponsiveness to cultured donor renal tubular epithelial cells. Initially recovering T cells were memory cells and were enriched for CD4+CD25+cells. Three patients are in sustained complete remissions of MM, despite loss of chimerism in two. Combined kidney/BMT with nonmyeloablative conditioning can achieve renal allograft tolerance and excellent myeloma responses, even in the presence of donor marrow rejection and antidonor alloresponses in vitro.

Published
2006
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45. New strategies for the control of viral infection in organ transplantation

Author

Tolkoff‐Rubin, N. E. and Rubin, H.

Abstract

Control of viral infection in organ transplant recipients requires attention to the following interventions: prevention, whenever possible of viral acquisition; the proper deployment of active and passive immunization, with hyperimmune globulin preparations directed against cytomegalovirus, hepatitis B, varicella, and, perhaps, respiratory syncytial virus, offering significant benefit when used appropriately; and the prescription of antiviral agents at critical points in the post‐transplant course. Two important principles should be kept in mind when approaching this problem: prevention is the goal, as treatment of established infection is fraught with difficulty; and effective preventative strategies must be linked to the intensity of the immunosuppressive program being employed. To achieve these goals, the addition of pre‐emptive therapy (therapy geared to a laboratory marker of impending disease or to escalation in the immunosuppressive program) to standard prophylactic regimens represents a significant advance.

Published
1995
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46. DIAGNOSIS OF TUBULAR INJURY IN RENAL TRANSPLANT PATIENTS BY A URINARY ASSAY FOR A PROXIMAL TUBLAR ANTIGEN THE ADENOSINEDEAMINASE-BINDING PROTEIN

Author

Tolkoff-Rubin, N. E., Cosimi, A. B., Delmonico, F. L., Delmonico, P. S., Thompson, R. E., Piper, D. J., Hansen, W. P., Bander, N. h., Finstad, C. L., Cordon-Cardo, Klotz, L. H., Old, L. J., and Rubin, R. H.

Abstract

Two murine monoclonal antibodies (URO-4 and URO-4a)—which detect different epitopes of a proximal tabular cell glycoprotein antigen the adenosine-deaminase-binding protein (ABP)—have been formatted into sandwich enzyme immunoassay for detection of ABP in the urine. Serial urine samples from 34 renal transplant patients during the first six months posttransplant were analyzed to determine the correlation of this test with clinical rejection and cyclosporin (CsA) nephrotoxicity.

Published
1986

47. Single-dose amoxicillin therapy of acute uncomplicated urinary tract infections in women

Author

Tolkoff-Rubin, N E, Wilson, M E, Zuromskis, P, Jacoby, I, Martin, A R, and Rubin, R H

Abstract

Of 210 women who were experiencing dysuria, frequent urination, pyuria, and significant bacteriuria and who were treated with a single 3-g dose of amoxicillin, 165 (79%) were cured of their original infections. Patients with infections that were negative by antibody-coated-bacteria assay were cured at a significantly higher rate than those with infections that were positive by antibody-coated-bacteria assay (90 versus 59%; P less than 0.001). Similarly, those with infections caused by amoxicillin-susceptible organisms were cured at a significantly higher rate than those with infections caused by resistant organisms (85 versus 50%; P less than 0.001). Of 27 patients who had infections caused by amoxicillin-susceptible organisms and who had relapses after single-dose therapy, 14 (52%) had relapses again after a conventional 10-day course of therapy, although all responded to a 6-week course. An additional 27 patients experiencing dysuria, frequent urination, and pyuria but who had a lower number of uropathogens in the urine (10(2) to 10(4.5)/ml of urine) were treated with single-dose therapy, with a 100% eradication of organisms and an 89% rate of symptomatic relief.

Published
1984
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48. Pharmacokinetics of intravenous amdinocillin in healthy subjects and patients with renal insufficiency

Author

Patel, I H, Bornemann, L D, Brocks, V M, Fang, L S, Tolkoff-Rubin, N E, and Rubin, R H

Abstract

Five healthy volunteers and 31 patients with various degrees of renal impairment received a 10-mg/kg intravenous dose of amdinocillin by infusion over 15 min to establish the disposition profile of the drug in plasma and urine. Both clearance from plasma and elimination rate constant showed a linear relationship with creatinine clearance. It was noted that in subjects with creatinine clearances of greater than 50 ml/min, the elimination half-life remained relatively constant; however, as the creatinine clearance decreased from 50 to 5 ml/min, there was a progressive rise in the elimination half-life. Despite the removal of the drug by hemodialysis (32 to 72% of the dose), concentrations of amdinocillin in plasma remained in the therapeutic range. In patients undergoing peritoneal dialysis, less than 4.0% of the infused dose was removed by dialysis during the hourly exchanges over a 14- to 18-h period. Although the clearance from plasma and the half-life of amdinocillin were altered up to fourfold in patients with creatinine clearances of less than 15 ml/min, the amdinocillin dosage per se may not need to be reduced for these patients if the frequency of dosing is reduced from six to three or four times daily. This is based on drug accumulation estimates of 56% from a regimen of 10 mg/kg every 8 h in these patients as compared with less than 10% from a regimen of 10 mg/kg every 4 h in subjects with normal renal function. In addition, supplemental doses may not be necessary during or at the end of hemodialysis for patients undergoing hemodialysis.

Published
1985
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49. Urinary tract infection: significance and management

Author

Tolkoff-Rubin, N E and Rubin, R H

Subjects
Adult, Male, Pyelonephritis, Age Factors, Middle Aged, Anti-Bacterial Agents, Pregnancy, Recurrence, Urinary Tract Infections, Humans, Female, Pregnancy Complications, Infectious, Child, Research Article, Aged
Published
1986

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