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R Munda

Publications and source records attributed to R Munda.

At least 37 records · Page 2Linked to original sources
PubMed1993

Bacterial translocation: a potential source for infection in acute pancreatitis.

Infections from enteric bacteria are a major cause of morbidity and mortality during acute pancreatitis (AP), but the pathways by which these organisms reach distant organs remains speculative. Experiments were conducted to determine if bacterial translocation could be a mechanism for infection during this disease. AP was induced in Lewis rats by i.v. infusion of caerulein (experiment I) or ligation of the head of the pancreas (experiment II). In a third experiment, rats were gavaged with 1 x 10(8) 14C-radiolabeled Escherichia coli and pancreatitis was induced with caerulein. Results in all three experiments showed that AP increased the number of viable bacteria recovered in peritoneal fluid, mesenteric lymph nodes (MLN), liver, lungs, and pancreas. Radionuclide counting indicated that AP enhanced the gut permeability to 14C E. coli. To estimate the impact of AP on the magnitude of translocation and on the ability of the host to clear bacteria, the nuclide and colony-forming units (CFU) ratios were calculated between animals with and without AP. Blood, peritoneal fluid, and MLN had the highest nuclide ratio. During AP, these tissues may be the principal routes for bacterial spreading from the gut lumen. Peritoneal fluid, pancreas, and lung were the tissues with the highest CFU ratio. Bacterial killing ability of these tissues is likely impaired during AP.

Acute Disease↗
PubMed1992

The induction of immunologic hyporesponsiveness by preoperative donor-specific transfusions and cyclosporine in human cadaveric transplants. A preliminary trial.

A prospective randomized preliminary trial was performed in patients undergoing cadaveric renal transplantation to determine the potential benefits, disadvantages, and logistic problems associated with the administration of donor-specific transfusions and cyclosporine initiated 24 hr before transplantation. Ten patients received DST followed by continuous intravenous CsA approximately 24 hr before cadaveric renal transplantation from the same donor. Twelve patients receiving sequential therapy with Minnesota antilymphoblast globulin, azathioprine, and steroids with subsequent conversion to CsA served as controls. Patient demographics and the donor characteristics were evenly matched in the two groups. While the study group had longer cold ischemia time and more evidence of renal dysfunction within the first two weeks, subsequent renal function was identical in the groups and there were fewer episodes of severe rejection requiring treatment with OKT3 within the first six months in the DST group (5 vs. 0, P less than 0.05), which also had less reactivity in mixed lymphocyte cultures against preserved donor-specific lymphocytes than did the control group (stimulation index 9.0 +/- 3.0 vs. 25.3 +/- 6.0, respectively, P less than 0.05). The need for dialysis, incidence of infections and other complications, and subsequent immunosuppressive therapy were not different in the two groups. It is concluded that DSTs and intravenous CsA initiated 24 hr prior to transplantation are capable of inducing reduced immunologic responsiveness against the specific donor. Patients treated with this therapy should receive organs from "ideal" donors without risk factors and cold ischemia time should not exceed 30 hr. Further clinical studies of this approach are warranted.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Evaluation of flowcytometric crossmatching in renal allograft recipients.

Forty-four cadaver renal allograft recipients who had flowcytometric cross-match (FCXM) testing and sequential quadruple immunosuppression were studied with respect to the number of rejection episodes and the functional viability of the graft in the first year after transplantation. Fourteen of these patients had antibodies to donor T cells by FCXM. All were negative by conventional crossmatch. Multiple-regression analysis with HLA mismatches, panel-reactive antibody (PRA) percentage, flowcytometric channel shifts and transplant number as independent variables revealed that transplant number and high PRA (> 50%) impacted (p < 0.05) on serum creatinine at 1 month and 1 year, and graft survival at 1 year. In first transplants, a positive FCXM had no impact on 1-year graft survival rates; however, in retransplants, a positive FCXM and/or high PRA had a significant negative impact on 1-year graft survival. This study indicates that the FCXM should be utilized for retransplant patients, and in patients with a high PRA, in an attempt to improve graft survival for these high-risk recipients.

Antilymphocyte Serum↗
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

Failure of orthoclone OKT3 retreatment in a pancreas transplant recipient with antimurine antibodies.

Orthoclone OKT3 is a murine monoclonal antibody that blocks the generation and function of T lymphocytes. It has been shown to be effective in reversing acute cellular rejection in solid organ transplants. However, potential development of antimurine antibodies restricts the duration that the drug can be used and the ability to reuse the drug. The case reported in this article illustrates the failure of retreatment with OKT3 when high titer (1:3200) antimurine antibodies are present. Lack of efficacy of the drug was documented by virtually undetectable circulating OKT3 levels in plasma, no decrease in T3 lymphocytes, and organ rejection. OKT3 should only be reused when immune monitoring (antimurine antibody status, lymphocyte subsets, and OKT3 plasma levels) is performed before, during, and after its use. Patients with high-titer anti-OKT3 antibody should not be retreated with OKT3.

Adult↗
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↗
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

Augmentation of donor-specific transfusion and cyclosporine effects with dietary linoleic acid.

Increased prostaglandin production is a possible mechanism for the immunosuppressive effects of both cyclosporine and blood transfusions. Therefore, dietary supplementation with linoleic acid, a prostaglandin precursor, combined with either modality could act synergistically. Intraabdominal cardiac allografts were performed from Buffalo rat donors to Lewis recipients. Transplant recipients received a single donor-specific transfusion, low-dose cyclosporine (CsA, 1 mg/kd/d x 7 days), dietary supplementation with linoleic acid (LA, 16% of total calories) or a combination of the three modalities. CsA, DST or LA alone significantly prolonged allograft survival. Both CsA and LA acted synergistically with DST in further prolongation of survival--however, animals receiving all three modalities achieved 100% long-term survival. Augmentation of transfusion- and cyclosporine-induced immunosuppression with dietary prostaglandin precursor is possible.

Animals↗