Search PubMed⌕ Search

Biomedical subjects

I Penn

Publications and source records attributed to I Penn.

At least 73 records · Page 4Linked to original sources
PubMed1991

Recent contributions to transplantation at the University of Cincinnati.

1. Clinical investigations at the University of Cincinnati have focused primarily on infection control, methods to increase donor-specific unresponsiveness, improvement in immunosuppression, donor maintenance and evaluation, posttransplant monitoring, and reduced-size livers for children. 2. Donor specific unresponsiveness (DSU) can be achieved frequently in recipients of both cadaver donor and living related donor kidneys by giving a single donor specific transfusion and CsA only 24 hours preoperatively with continuing triple immunosuppressive therapy. 3. Prednisone can be withdrawn from almost all patients with no rejection by 1 year with significant improvement in blood pressure, daily insulin requirement in diabetics, total blood cholesterol, and low density lipoproteins (LDL). 4. Oral ketoconazole 200 mg/day can be used safely to block the hepatic metabolism of CsA and reduce the amount of CsA administered by an average of 77-88%. This is of great economic consequence to lower income patients and patients with poor drug absorption. 5. Eighteen patients with SLE who received 23 kidney transplantations had an increase in graft loss in the first 6 months but the rate of graft loss after 6 months was almost identical to other ESRD patients. 6. The Cincinnati Transplant Tumor Registry has data on about 8,000 patients. Except for those with CNS tumors, patients with active cancers should not be used as donors. However, donors with previous curative procedures should not be excluded automatically. Cancers arising in immunosuppressed transplant recipients that have a higher incidence than the general population (expressed as percentage of treated cancers) are: lymphomas (22% vs 5%), lip cancers (7% vs 0.3%), Kaposi's sarcoma (6% vs less than 0.1%), vulva and perineal cancers (4% vs 0.6%), hepatobiliary cancers (2.5% vs 1.0%) and sarcomas (1.8% vs 0.5%). Other cancers have about the same-distribution. 7. Immunologic monitoring during OKT3 therapy is particularly useful in re-treatment and treatment of pediatric liver patients when increased doses of the drug may be necessary. 8. The MEGX test has been found to be a major predictor of primary non-function of the transplanted liver, and it is also useful in predicting the risks of dying from liver disease. 9. Reduced-size livers have been used in 37 patients, representing almost half of all pediatric liver transplants. Survival with reduced-size grafts (91% at 1 year) compared favorably with survival of whole organs (79% at 1 year). The benefit is particularly dramatic in infants with biliary atresia (100% 1-year graft survival in 24 patients, median age 11 months).(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗
PubMed1991

Efficacy of induction therapy in cadaveric renal transplantation comparing rabbit antithymocyte serum and Minnesota antilymphoblast globulin.

From August 1986 to July 1989, 98 patients receiving primary cadaveric kidney transplants received either RATS (n = 50) or MALG (n = 48) during the induction phase of a quadruple immunosuppressive protocol. Patient groups were well matched. The duration of RATS and MALG treatment and the time of CyA induction were equivalent. Serum creatinine and rejection episodes up to 1 year were not statistically different. Hematologic side effects resulted in dose reduction of MALG in 42% of patients without adverse rejection results. In the RATS group, no dosage reductions were required. One-year patient survivals (96% to 100%), and 1-year graft survival (82% to 85%) were not significantly different in the 2 groups. Infectious complications were 30% higher in the MALG group and a significant factor in 2 deaths. Monitoring of lymphocyte subsets revealed insignificant differences in the percent of decrease of each cell population between MALG and RATS groups during induction.

Adult↗
PubMed1990

HLA and Kaposi's sarcoma in solid organ transplantation.

Of 188 cases of Kaposi's sarcoma arising de novo after transplantation, HLA-A, -B typing was available for 135 and HLA-DR typing available for 67. Compared to the reported HLA phenotype frequencies of renal transplant recipients in the Southeast Organ Procurement Foundation (SEOPF), there is a significantly decreased frequency of HLA-A1 and HLA-B7, and increased frequency of HLA-B5, -B8, -B18, and -DR5. The most striking characteristic of the Kaposi's sarcoma group was its ethnic background. Fifty-six percent of patients were Italian, Greek, Jewish, or Arabic. When this ethnic background is considered, the expected HLA phenotype frequencies are almost exactly the same as in the Kaposi's sarcoma population. The quality of donor-recipient HLA match was evaluable for 106 patients. Only 22% had four or more mismatches, and 59% had at least two antigens matched. This argues against poor donor-recipient matching as a risk factor for developing Kaposi's sarcoma after transplantation.

HLA Antigens↗
PubMed1990

Antimurine antibody formation following OKT3 therapy.

OKT3 is an IgG2a murine monoclonal antibody directed against the CD3 antigen receptor of human T lymphocytes. A major concern with OKT3 treatment in solid organ transplant recipients is the development of antimouse antibody, which may preclude retreatment with this agent. We have administered OKT3 on 215 occasions (150 renal, 34 hepatic, 26 cardiac, 5 pancreatic) in 179 patients between April 1982 and December 1988. The mean duration of treatment was 10.5 days (range, 2-22 days). Antimouse antibody data were analyzed on the most recent 133 treatment courses where the antibody status was available pretreatment. Determination of antimouse antibody production was elicited by ELISA technology at days 0, 7, 14, and 28 of OKT3 treatment. Patients were categorized according to the antibody response as follows: (a) absence of antibody; (b) low titer (1:100); or (c) high titer (greater than or equal to 1:1000). Our earlier experience has demonstrated that retreatment with OKT3 is successful in groups a and b. The development of antimurine antibodies was analyzed with regard to the following parameters: (1) The duration of OKT3 treatment; (2) treatment type (prophylactic, primary, or secondary); (3) primary treatment or retreatment; (4) concomitant immunosuppressive regimen (double or triple therapy); (5) dosage of concomitant immunosuppressive drugs; and (6) transplant organ type. The following results were obtained. (1) Duration of treatment had no effect on antibody production (11.0 days in antibody negative and 10.0 days in antibody positive). (2) There was no difference in antibody formation rates for the first treatment of OKT3 when it was used as prophylaxis (26%), primary (19%), or secondary (27%) therapy. (3) Antibody formation rate with first treatment was 29%; with retreatment, patients who were antibody negative following first treatment became positive in 28% of cases, and retreated patients who were low titer positive following first treatment converted to high titer in 57% of cases. (4) Antibody formation was higher in patients receiving double immunosuppressive therapy (36%) than in those receiving triple immunosuppressive therapy (21%) during OKT3 treatment. (5) Concomitant immunosuppression was lower in the antibody-positive group during OKT3 therapy: steroids, 61 mg/day vs. 52 mg/day; azathioprine, 89 mg/day vs. 66 mg/day; CsA, 317 mg/day vs. 186 mg/day. (6) Antibody formation rates were lower in non-renal transplants following first treatment with OKT3 (liver 17%, heart 17%, kidney 28%); this reflects the higher doses of concomitant immunosuppressive therapy used in nonrenal transplants.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Occurrence of cancers in immunosuppressed organ transplant recipients.

The findings in this study emphasize the need for lifetime follow-up of organ transplant recipients. Currently, approximately 6% of organ transplant recipients have developed neoplasms and 1% have died of their tumors. Most deaths have been from high-grade carcinomas of various organs or from NHLs. Fortunately, a high percentage of posttransplant tumors are low-grade malignancies that are readily amenable to treatment. The future holds promise. Attempts are being made to modify the present blunderbuss attack on the immune system with more specific methods of control of certain of its components. Much work is currently being done to induce states of immune unresponsiveness directed specifically, and only, at the foreign antigens of the allograft. Hopefully these efforts will eliminate the need for long-term or intense immunosuppressive therapy and the problem of posttransplant malignancies will be relegated to a footnote in the history of organ transplantation.

Bone Marrow Transplantation↗
PubMed1990

Lymphoproliferative diseases in disorders of the immune system.

Severe immunodeficiency diseases are complicated by the development of malignancies of the immune system itself, mainly non-Hodgkin's lymphoma (NHLs). These occur in immunosuppressed organ allograft recipients; in cancer chemotherapy patients; in patients with primary immunodeficiency diseases; in chronic dialysis patients; in victims of the Acquired Immunodeficiency Syndrome (AIDS); and in persons with various autoimmune diseases either untreated or given immunosuppressive therapy. Most of these NHLs are reticulum cell sarcomas or immunoblastic sarcomas. Immunologically, most are of B-cell origin. Most tumors are extranodal in distribution. They show a remarkable predilection for the brain. Possible causes of the NHLs include oncogenic viruses; disturbed immune surveillance; chronic antigenic stimulation; impaired immunoregulation; carcinogenic effects of immunosuppressive, cytotoxic or other drugs; and genetic susceptibility to lymphomagenesis.

Humans↗
PubMed1989

Successful retreatment of allograft rejection with OKT3.

OKT3 is a murine monoclonal antibody to the CD3 antigen of human T lymphocytes. The production of human antimurine antibodies after treatment with OKT3 has been perceived as a major limitation to its extended use and reuse. Treatment of 142 patients with 168 courses of OKT3 resulted in the development of antimouse antibody in 28% of the patients. Twenty-six patients (16 kidney, 6 liver, 3 heart, 1 pancreas) have been retreated with 27 courses of OKT3. Eighteen patients had no antimurine antibodies present, and the rejection reversal rate was 83% (15/18). Six patients had a low-titer antimurine antibody present, and rejection reversal occurred in 5 (83%). Rejection was not reversed in 2 patients with a high-titer antibody. Development of antimurine antibody was more frequent in renal transplant recipients (33%) than in hepatic (12%) or cardiac transplant recipients (18%). We believe that this reflects the fact that concomitant immunosuppressive therapy is more likely to be reduced during OKT3 therapy in renal transplant recipients than in hepatic or cardiac transplant recipients. Retreatment of patients with no anti-OKT3 antibody resulted in depletion of CD3+ cells from the peripheral blood, but it took longer than in patients being treated with OKT3 for the first time. Similarly, serum OKT3 levels rose more slowly in retreated patients compared to first treatment. In retreating patients with a low-titer antimurine antibody, it often was necessary to increase the dose of OKT3 in order to achieve adequate serum OKT3 levels and to deplete CD3+ cells. De novo antimurine antibody developed in 4 of the 18 (22%) antibody-negative patients who were retreated. In conclusion, retreatment with OKT3 should not be considered unless the antibody status of the patient is known. Development of low-titer antibodies does not preclude successful retreatment with OKT3; however, alternate antirejection therapy should be used in patients with high-titer antimurine responses.

Antibodies, Anti-Idiotypic↗
PubMed1989

Prophylactic use of OKT3 in immunologic high-risk cadaver renal transplant recipients.

Prophylactic OKT3 was administered to 27 immunologic high-risk cadaver renal transplant recipients (multiple transplant and/or panel reactive antibody greater than 50%) as part of a sequential immunosuppressive protocol consisting of OKT3, prednisone, azathioprine, and cyclosporine. The first dose of OKT3 was administered intraoperatively. Patient survival was 100% with a mean follow-up period of 13 months. Graft survival at 1 year was 70% (19 of 27). Eight grafts were lost during the first 6 weeks. Causes of graft loss were hyperacute rejection or primary nonfunction (4), irreversible rejection (2), and technical (2). After the first month, single rejection episodes occurred in four patients and multiple rejection episodes in three patients; all were successfully reversed, and no further graft losses were encountered. Mean serum creatinine level at 1 month posttransplant was 141 mumol/L (1.6 mg/dL), and the average serum creatinine has remained at that level during the follow-up period. No serious infections were encountered. Prophylactic OKT3 administration resulted in depletion of CD3+ lymphocytes from the peripheral circulation throughout therapy, as well as the development of therapeutic serum OKT3 levels. Five of the 27 (22%) patients developed antimurine antibodies during or after OKT3 therapy; four of these patients had low-titer antimurine antibody, and one had high-titer antimurine antibody. First-dose reactions were generally mild in this group of patients. Prophylactic use of OKT3 in this patient population resulted in superior graft survival when compared with a similar group of patients not receiving OKT3.

Adult↗