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Biomedical subjects

R M Hoffmann

Publications and source records attributed to R M Hoffmann.

At least 73 records · Page 4Linked to original sources

Cadaveric renal transplantation in the cyclosporine and OKT3 eras: an update of the University of Wisconsin-Madison experience.

1. Quadruple immunosuppression yields excellent early renal allograft survival in primary renal transplant recipients when compared with non-primary renal transplant recipients. Although significant, the difference between primary and nonprimary recipients at 5 years has narrowed considerably (8%). 2. No beneficial effect of HLA or DR matching was noted in this study in primary transplant recipients. However, a trend toward improved graft survival was noted when patients with greater than or equal to 3 antigens matched or less than 3 antigens mismatched were compared to their counterparts. Further analysis of variables related to graft loss is required before statements regarding this trend can be made. 3. Significantly better results in nonprimary renal transplantation continues to be seen in DR matched recipients. Additionally, the use of OKT3 rather than ALG in DR matched recipients has resulted in a 92.3% 3-year allograft survival despite over half of these patients being highly sensitized. 4. Further follow-up of 2 high-risk groups of patients (diabetics and elderly patients) revealed significant decreases in patient survival at 5 years. This difference was not apparent in our earlier results (3-year follow-up) published in Clinical Transplants 1987. Despite this difference, we believe renal transplantation should continue to be offered to diabetic and elderly patients without other contraindications to transplantation. 5. The availability of the monoclonal antibody OKT3 during the CsA era has resulted in a trend toward improved patient and graft survival when compared with patients in the CsA pre-OKT3 era. This trend toward improved survival is also seen in the high-risk diabetic recipients.

Antibodies, Monoclonal↗

The Transosteal implant in the prosthodontic reconstruction of the edentulous mandible.

It is the purpose of this article to review transosteal implants, specifically the Mandibular Staple Bone Plate and the Transmandibular Implant, in regard to their clinical prosthodontic applications. In addition, those aspects of prosthodontic treatment shared will be highlighted and the differences in the techniques will be reviewed.

Dental Implantation, Endosseous↗

Clonal analysis of liver-derived T cells of patients with primary biliary cirrhosis.

Lymphocyte infiltration in liver tissue is one important histological finding in primary biliary cirrhosis (PBC). So far, functional analyses of lymphocytes in PBC have focused on circulating lymphocytes, whereas lymphocytes at the involved site, the liver, have not been examined functionally. We have established interleukin 2 (IL-2)-dependent T lymphocyte lines (TLL) and clones (TLC) from liver biopsies of 14 patients with PBC. Phenotypic analysis using the monoclonal antibodies MT910 (CD2), MT811 (CD8), and MT151 (CD4) revealed that in nine of 14 TLL cytotoxic-suppressor T cells predominated (CD8+:52-84%; CD4+:14-48%), whereas in five of 14 TLL a preponderance of the CD4+ subpopulation was found (CD4+:56-73%; CD8+:28-45%). From 10 patients 137 TLC were generated which phenotypically correlated to the TLLs. We have tested the cytotoxic potential of seven TLL and 43 TLC in LDCC (lectin-dependent cell-mediated cytotoxicity), NK (natural killing) and ADCC (antibody-dependent cell-mediated cytotoxicity) assays. All TLL and all but one CD8+ TLC tested showed high activity in the LDCC assay, reflecting the cytolytic activity of cytotoxic T cells (CTL). CD4+ clones with LDCC activity were rarely found. NK activity and K cell activity could only be found in two clones. For the first time TLC and TLL from liver tissue of PBC patients could be generated. The high cytotoxic activity displayed by T cells derived from the liver indicates an important role for this immunological mechanism in the tissue damaging process.

Adult↗

Cadaveric renal transplantation in the cyclosporine and OKT3 eras.

With advances in clinical immunosuppression, results in organ transplantation continue to improve. During a 52-month period, 507 cadaver renal transplants were performed, including 435 primary and 72 nonprimary transplants. All patients were managed with quadruple immunosuppression (prednisone, azathioprine, sequential MALG and cyclosporine). Our experience is divided into pre-OKT3 (n = 228) and OKT3 (n = 279) eras. All kidneys were harvested locally and preserved with pulsatile machine perfusion. The mean duration of preservation was 30.1 hours, with an organ utilization rate of 98.1%. The preservation-related dialysis rate was 13.6%, and primary nonfunction occurred in 8 kidneys (1.6%). Actuarial patient survival in primary and secondary transplant recipients was 90% at 3 years. Overall primary graft survival was 81.6% and nonprimary graft survival, 61.1%. However, the current OKT3 era is characterized by improved patient survival (98% vs 90%, p = 0.001) and primary graft survival (91% vs 80%, p = 0.002) at 1 year when compared with the previous era. Forty-nine patients have received OKT3 therapy, with 31 grafts (63.3%) successfully rescued. Cadaveric renal transplantation with machine preservation, quadruple therapy, and OKT3 rescue is associated with excellent early graft function, reduced acute rejection, and improved patient and allograft survival, even in high-risk recipients.

Adolescent↗

Cytolytic T cell clones derived from liver tissue of patients with chronic hepatitis B.

To study the role of cell-mediated immunity in chronic hepatitis B (cHB) we have cloned T cells from liver biopsies of 14 patients with cHB. As a first step, T cell lines were established from lymphocytes infiltrating the liver by culturing the biopsied specimens with autologous feeder cells and interleukin 2 (IL2). Fifty-eight clones obtained by limiting dilution showed phenotypic stability over periods of 2-26 weeks. Of the 58 clones 50 were of the "cytotoxic/suppressor" T cell subset (CD8) as defined by the monoclonal antibody T811. Only 8 of 58 clones were of the "helper/inducer" phenotype (CD4) as defined by the monoclonal antibody T151. Functional studies on 9 clones (7 of CD8+ phenotype, 2 of CD4+ phenotype) revealed high cytotoxic activity of all of these clones in a lectin-dependent cell-mediated cytotoxicity assay reflecting the killing capacity of cytotoxic T lymphocytes. All 9 clones lacked significant natural killer activity, while two additional CD8+ clones that also expressed the VEP13 antigen showed significant natural killer activity. For none of the clones tested could killer cell activity (ADCC) be demonstrated. The studies demonstrate that the clonal expansion of T lymphocytes from liver biopsies of patients with cHB in the absence of detectable antigen is possible. The propagation of in vivo activated cytolytic T lymphocytes points to an active role of these cells in the pathogenesis of this disease.

Adult↗

Effects of hypothermic kidney preservation on the isolated perfused kidney: a comparison of reperfusion methods.

Two isolated-perfused kidney methods were used to study the effects of hypothermic preservation on renal function in dog kidneys. The isolated-machine-perfused kidney (IMPK) used an in vitro perfusion technique--the perfusate was a Krebs-bicarbonate type delivered to the kidney at 37 degrees C by a mechanical pump at a constant pressure (100 mm Hg). The isolated-blood-perfused kidney (IBPK) utilized transplantation of the preserved kidney to the femoral vasculature. Renal function (urine analysis) was determined over a 1-hr reperfusion interval and included GFR (creatinine clearance), urine formation, and Na+ reabsorption. Kidneys preserved for only 24 hr by cold storage in either Collins'--C3 solution or in hypotonic citrate and kidneys hypothermically perfused for 24 hr demonstrated greater retention of renal function when reperfused by blood (IBPK) than with the in vitro perfusate (IMPK). The GFR was reduced by 38-58% when tested with the IBPK, but by 80-90% when tested with the IMPK. Na+ reabsorption was normal (97%) with blood reperfusion but was reduced to 36-50% in cold-stored kidneys and 82% in hypothermically perfused kidneys determined by machine reperfusion (IMPK). However, kidneys perfused for 72 hr demonstrated more similar renal functions when tested by either IMPK or IBPK. GFR was reduced to 20% (IBPK) and 11% (IMPK) and Na+ reabsorption averaged 76-85% (IBPK or IMPK). These results suggest that either reperfusion method is suitable for determining the effects of renal preservation on kidney function in kidneys preserved for 72 hr but, for short-term preserved kidneys (24 hr), the IBPK model may be preferred.

Animals↗

Combination perfusion-cold storage for optimum cadaver kidney function and utilization.

Dog kidneys were perfused with a newly developed perfusate containing adenosine and PO4 for 48 hr, stored in the same perfusate for an additional 24 hr without perfusion (total preservation time:72 hr), and transplanted with immediate contralateral nephrectomy. Posttransplant renal function and biochemical analysis of the kidneys revealed practically no additional preservation-induced damage during the cold storage period. Serum creatinine levels reached normal between the third and eighth day posttransplant. This preservation method may be the method of choice for patients receiving postoperative cyclosporine therapy--and, in addition, facilitate organ sharing between transplant centers, thus reducing wastage of cadaveric kidneys.

Animals↗

Synthetic perfusate for kidney preservation. Its use in 72-hour preservation of dog kidneys.

Hydroxyethyl starch (HES) was used as the sole colloid for oncotic support in a perfusate for successful (12 of 12 survivors) 72-hour kidney preservation by hypothermic-pulsatile perfusion. Posttransplant renal function was consistently better than that obtained with other perfusates commonly used in continuous perfusion preservation. Often the posttransplant serum creatinine levels rose to only 1.6 mg/dL and rapidly returned to normal (1.0 mg/dL). The perfusate included, in addition to HES, gluconate as the major anion in place of chloride. Perfusate containing high levels of potassium produces results equal to those with high levels of sodium. This is, to our knowledge, the first report of consecutive successful 72-hour preservation of canine kidneys using a purely synthetic perfusate devoid of animal-derived protein for colloid oncotic support.

Animals↗

Beneficial effects of adenosine and phosphate in kidney preservation.

A new perfusate developed in the animal laboratory has been used in our clinical transplantation program in the last year. This perfusate provides excellent clinical results even with less-than-ideal kidneys, as manifested by an 83% immediate function rate and a 96.5% one-month graft survival. Optimum utilization of all donors referred to a transplant center may lessen the problem of insufficient donor organs. Continued basic research in the laboratory to optimize perfusion preservation may produce even better perfusates that can be adapted to the clinical situation and further improve graft survival.

Adenosine↗