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Biomedical subjects

R T Schweizer

Publications and source records attributed to R T Schweizer.

At least 55 records · Page 3Linked to original sources

Progress in experimental porcine small-bowel transplantation.

Studies in large animals are needed to overcome technical complications, allograft rejection, and graft-vs-host disease, which are major problems that prevent clinical application of small-bowel transplantation. The small bowel was allografted heterotopically or orthotopically into 30 pigs with the use of cyclosporine, prednisone, and azathioprine. When cyclosporine was given orally to heterotopically transplantation recipients, rejection was frequent, and graft-vs-host disease caused one death. After 30 days of intravenous cyclosporine followed by oral administration, no rejection occurred. Graft-vs-host disease was mild or absent, and there were some long-term survivors. Technical failures were relatively infrequent, but death from sepsis, eg, intra-abdominal abscess, occurred in 17% (5/30). Anastomoses of donor superior mesenteric vein to recipient portal vein offered no advantages over systemic venous drainage. Although the high cyclosporine levels used would be intolerable in humans, these results indicate that successful small-bowel transplantation can be achieved with adequate immunosuppression in a large animal.

Administration, Oral↗

Use of oxygen radical scavengers on autografted pig kidneys after warm ischemia and 48-hour perfusion preservation.

Oxygen free radicals generated during the reperfusion of an ischemic organ may cause further cellular injury; removal of these oxygen radicals by scavengers protects tissue from reperfusion injury. Thus, oxygen radical scavengers could protect kidneys after warm ischemia and long hypothermic perfusion. Porcine kidneys were incubated at 37 degrees C for 45 minutes, placed on a pulsatile perfusion apparatus at 7 degrees C for 48 hours, and then autografted to iliac vessels. Superoxide dismutase (10 mg) and catalase (10 mg) in 10 mL of phosphate-buffered saline solution were infused into the renal artery during a three-minute interval before reperfusion. The kidneys treated with the superoxide dismutase-catalase solution had significantly improved function compared with controls receiving only phosphate-buffered saline solution. The mean (+/- SEM) serum creatinine level on postoperative day 5 was 510 +/- 100 mumol/L (5.75 +/- 1.12 mg/dL) (n = 12) vs the control value of 840 +/- 90 mumol/L (9.54 +/- 1.01 mg/dL) (n = 11). There was more extensive cellular damage in the control kidneys. This demonstrates the efficacy of oxygen radical scavengers in protecting pig kidneys after warm ischemia and prolonged preservation.

Animals↗

Renal transplantation at Hartford Hospital: results of combined and flexible immunosuppression.

1. Three groups of first cadaver kidney transplant recipients at Hartford Hospital were analyzed. All received AZA and P, and most received pretransplant blood transfusions. The first group, 41 patients transplanted from 1977-1979, had a 2 year graft survival of 49%; the second group, 72 patients transplanted from 1980 to 1984 had an emphasis on DR typing and 2-year graft survival of 61%. The third group had the addition of CsA (triple immunosuppression) from 1984 to October, 1988. These 200 patients had a 2-year graft survival of 87%. The 2-year patient survival was 82%, 85%, and 94% for the 3 groups, respectively. 2. Triple immunosuppression resulted in less frequent and less severe rejection activity. There was no increase in serious infection and no significant elevation in mean serum creatinine at a 2-year follow-up, when compared to a control group receiving AZA and P. 3. DST was used selectively for one haplotype living-related donor kidney transplants, and in HLA-identical sibling kidney transplantation. Triple immunosuppression was also used in living-related donor kidney transplants, but in a very low-dose range. Only 3 of 58 grafts in living-related donor kidney transplants have been lost in the past 4 years; none due to rejection. 4. OKT3 therapy has been used primarily for steroid-resistant rejection, usually resulting in reversal, but also in a significant increase in CMV infection. When an "OKT3 available" group of cadaver kidney transplant recipients was compared to a previous control group, OKT3 therapy did not appear to improve the overall results. 5. Patients receiving retransplantation experienced a better success rate than reported at many other centers, (72% graft survival at 2 years). The use of OKT3 or ATG and DR matching contributed to the success. 6. The average ATN rate for all perfused kidneys was 36%; 50% for those preserved longer than 28 hours. Imported kidneys preserved with Euro Collins solution had a 63% ATN rate versus 36% for locally procured kidneys. There was no significant difference in graft survival in patients with or without posttransplant ATN.

Adolescent↗

The LAV/HTLV-III virus may evade elimination by the immune system by inducing low zone tolerance to itself.

The acquired immunodeficiency syndrome (AIDS) is caused by the LAV/HTLV-III virus. The incubation period for AIDS is prolonged and on the order of years. We hypothesize that during this prolonged incubation period the LAV/HTLV-III virus is replicating very slowly and is present in extremely low concentrations. The concentrations of the virus may be low enough that the virus induces a low zone tolerance to itself in the T-cell arm of the immune system. B-cells which are resistant to direct low dose tolerance induction may remain responsive to the LAV/HTLV-III virus in a direct fashion without specific helper T-cells. Thus, anti-LAV/HTLV-III antibody may be produced even though the more important cellular immune response has been crippled by the virus. We also outline two hypothetical approaches for breaking this tolerance and restoring the cellular immune response to the LAV/HTLV-III virus.

Acquired Immunodeficiency Syndrome↗