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Biomedical subjects

F T Rapaport

Publications and source records attributed to F T Rapaport.

At least 73 records · Page 4Linked to original sources
PubMed1989

Malakoplakia in renal transplantation: an expression of altered tissue reactivity under immunosuppression.

This report describes the successful treatment in a transplant recipient of a case of MK originating from the native urinary tract. As demonstrated, MK may pursue unexpected patterns to which conventional therapeutic guidelines may not be applicable. The type of surgical intervention used must be dictated by the extent and location of the disease and its complications. Withdrawal of immunosuppressive medication was useful in improving the patient's prognosis.

Adult↗
PubMed1988

Synergistic effects of combined immunosuppressive modulation. I. Unresponsiveness to dendritic cell-depleted renal allografts in dogs exposed to total-lymphoid irradiation.

Attenuation of the allogeneic stimulus provided by dendritic cells (DC) was achieved by irradiation of the donors, followed by their reconstitution with bone marrow from the prospective DLA-identical recipient. Following long-term (131-187 days) recovery free of graft-versus-host (GVH) disease, the chimeric kidneys were placed into the corresponding recipients; such allografts were rejected at 55, 55, and 60 days, respectively. Four other recipients were conditioned with 1750-1790 cgy of total lymphoid irradiation (TLI) and were then given a similar chimeric kidney from the corresponding partner. These allografts currently survive for 296, 295, 290, and 252 days, respectively. A third group of four dogs was exposed to TLI prior to transplantation of a normal DLA-identical kidney. These grafts were rejected at 20, 42, 46, and 242 days, respectively. Thirteen DLA-identical renal allografts transplanted into normal dogs survived for 13-38 days (mean survival time = 28.6 days). Depletion of allogeneic DC alone, or TLI alone, produced relative prolongations in allograft survival in canine recipients. Combined use of these two modalities, however, resulted in long-term allogeneic unresponsiveness in the recipients.

Animals↗
PubMed1987

Implication of Ia-positive bone marrow interstitial stem cells in the induction of unresponsiveness to canine renal allografts.

The removal from stored autologous host bone marrow of a monocytoid cell population by exposure to methylprednisolone is associated with successful introduction of unresponsiveness to renal allografts in irradiated recipients reconstituted with such treated marrow. The eliminated cells are a prominent component of the canine long bone marrow interstitium and share a number of important properties with dendritic cells (DC), including size and shape; poor or nonadherence to plastic or glass surfaces; negative staining for neutral esterase, acid phosphatase, or peroxidase; nonphagocytic; Ia positive, but negative for IgG or IgM; ability to act as accessory cells in augmenting the intensity of allogeneic mixed-lymphocyte reactions. Both cell types are of bone marrow origin and are susceptible to steroids in vitro. The results suggest that the bone marrow interstitial cells identified in the course of this study may be enriched with populations of canine dendritic cell precursors and dendritic cells at various stages of differentiation. The detection of a receptor site for Helix promatia on the surface of such cells may be of usefulness in their further characterization and in the analysis of their precise role in the modulation of allogeneic unresponsiveness.

Animals↗
PubMed1987

Value of percutaneous core needle biopsy in the differential diagnosis of renal transplant dysfunction.

The value of percutaneous core needle biopsy in the differentiation of rejection from other causes of renal allograft dysfunction, and its subsequent effect on patient management were assessed in 64 consecutive biopsies performed on 34 patients in whom the clinical diagnosis was was uncertain. A complete clinical, biochemical and radiographic assessment was made in each patient before biopsy. Only 1 biopsy (1.6 per cent) yielded tissue inadequate for evaluation, while another biopsy caused a renal artery pseudoaneurysm that ruptured and resulted in graft loss. In 27 of these 64 biopsies (42 per cent) the results differed from the pre-biopsy diagnosis and directly affected patient management, particularly the use of steroids. The remaining biopsy specimens were helpful to confirm uncertain clinical impressions, and allowed accurate counseling for patients and family. Biopsies were of special usefulness in separating acute rejection from complications, such as acute tubular necrosis, cytomegalovirus infections, recurrence of original disease, cyclosporin toxicity and acute superimposed-upon chronic rejection. Of 64 biopsies 22 (34.3 per cent) demonstrated the absence of rejection and 8 demonstrated chronic rejection (12.5 per cent), thereby averting the use of steroids in 46.8 per cent of the patients. All patients with evidence of severe small vessel disease and/or antibody-mediated rejection eventually lost the grafts, including 2 with cytomegalovirus glomerulopathy who also suffered such vascular changes. These data highlight the extreme usefulness of needle biopsy in the evaluation and management of renal allograft dysfunction.

Biopsy, Needle↗
PubMed1987

Immunohistologic analysis of human renal allograft dysfunction.

The value of percutaneous core needle biopsy in the immunohistological evaluation of renal allograft dysfunction was studied in 72 consecutive biopsies performed in 42 patients. The phenotypes of infiltrating cells mediating graft destruction were identified with monoclonal antibodies and immunoperoxidase staining techniques. Light microscopy, electron microscopy, and immunofluorescence staining were performed in all biopsies. Biopsies were divided into groups depending on their classification on the basis of standard histologic criteria, i.e., acute tubular necrosis (ATN), acute interstitial rejection, acute vascular rejection, chronic rejection and renal disease in native kidneys (RDNK) of nontransplant patients. Immunohistologic analysis of graft biopsies showed a significant increase in Leu 1 (pan-T cells), (P less than 0.001), Leu 2 (cytotoxic/suppressor cells) (P less than 0.001), and Leu 3 cells (P less than .05) in acute interstitial rejection. The expression of DR antigen was significantly increased in both acute (P less than .025) and chronic (P less than .05) rejection, when compared with the findings in ATN biopsies. Leu M1 (monocytes/activated T cells) and Leu 10 (B cells/macrophages) were significantly increased (P less than 0.05 and P less than .005, respectively) in acute interstitial rejection only. The helper/suppressor ratio of infiltrating cells showed no significant change in any clinopathologic category. There was no correlation between the cell populations infiltrating the graft and those monitored in the peripheral blood. Allograft mononuclear cell infiltrates in cyclosporine (CsA) vs. azathioprine-treated patients revealed significantly fewer Leu 2 (P less than .05) and Leu M1 (P less than .05) cell populations in CsA patients during acute rejection. In 32 of these 72 biopsies (44.4%), the biopsy results provided a direct contraindication to the use of steroids, by allowing differentiation between allograft rejection and other causes of graft dysfunction. A total of 38% of the biopsies yielded a histological diagnosis that contradicted the clinical pre-biopsy diagnosis. All allografts showing evidence of severe small vessel disease and/or antibody-mediated rejection eventually were lost. These data highlight the usefulness of needle biopsy material as a guide to the study of intragraft immune events and to clinical management of recipients.

Acute Kidney Injury↗
PubMed1987

The protective effect of calcium inhibitors and of captopril on the renal microcirculation during reperfusion.

Reperfusion injury is increasingly recognized as a key factor in the development of posttransplant acute tubular necrosis. Previous studies have shown that addition of the calmodulin inhibitor trifluoperazine (TFP) to Collins' flush solution protected the cortical microcirculatory integrity and dramatically improved renal viability after transplantation. The present report describes the protective effect(s) of TFP in the course of reperfusion injury. Twenty mongrel dogs underwent bilateral nephrectomy; in each instance, the left kidney was flushed immediately with 250 ml of cold Collins' solution, and the right kidney was flushed with the same solution containing TFP, 5 mg/L. After 48 and 72 hr of preservation, each kidney was connected through silastic shunts to the femoral vessels of another dog. The mean renal blood flow (RBF) immediately after reperfusion was 2.2 ml/g/min and 1.7 ml/g/min in the left and right kidneys, respectively, and was similar to mean RBF measurements prior to nephrectomy. After 15 min of reperfusion, there was a sharp decrease in mean RBF in the Collins' flushed kidneys, which persisted after 60 min of reperfusion (0.37 ml/g/min). In contrast, there was only a mild decrease in mean RBF in the TFP-flushed kidneys (1.27 ml/g/min). A partial explanation for the favorable effect of TFP may be related to the inability of the ischemic cell to handle the increased calcium load associated with reperfusion (calcium paradox). In a test of this possibility, 0.5 mg/kg of verapamil, a calcium channel blocker, was infused during reperfusion. No beneficial effects of this drug were noted in either Collins' or TFP-flushed kidneys (n = 10). However, when 1.25 mg/kg of captopril, an angiotensin-converting enzyme inhibitor, was infused at the time of reperfusion, a dramatic amelioration of the reperfusion injury occurred in the Collins' flushed kidneys (1.2 ml/g/min) (n = 10). Taken together, these data suggest that the damage to cold-preserved kidneys flushed with Collins' solution alone may occur at the time of actual reperfusion. Such reperfusion damage is ameliorated by TFP and captopril. The known relationship between calcium and the effect of angiotensin on the vascular smooth muscle cell may explain in part the protective role of calcium inhibitors placed in preserved kidneys prior to reperfusion.

Angiotensin II↗
PubMed1987

Preoperative preparation of high-risk, specifically hyperimmunized canine renal allograft recipients with total-lymphoid irradiation and cyclosporine.

Hyperimmunized subjects are a particularly high-risk and rapidly growing group in the patient population awaiting renal transplantation. In a search for methods designed to ameliorate the prognosis in such cases, dogs of defined DLA genotype were sensitized with DLA incompatible skin allografts and injections of buffy coat. Each recipient was challenged with a renal allograft bearing the same DLA incompatibilities. Five dogs received kidney transplants, without any other treatment, and rejected their transplants at 2.5, 4, 5, 6, and 6.5 days, respectively. Another four dogs were given a 9-11-week course (1760 +/- 35 cGy) of total-lymphoid irradiation (TLI), followed by rabbit antithymocyte globulin (ATG); these animals rejected their renal allografts at 7, 8, 14, and 17 days, respectively. Five other dogs were treated with TLI and received cyclosporine (CsA) and methylprednisolone (MPd) daily until graft rejection. Their renal allografts survived for 7.5, 8.5, 20, 62, and 227 days, respectively. Renal allografts placed in normal recipients under the same conditions of donor-recipient DLA incompatibility had a mean survival time of 12.4 days (range: 10-18 days). At the time of transplantation, the specific anti-DLA antibody titers in the recipients were 81 to 243 in the untreated dogs; 27 to 81 in the TLI-ATG-treated group, and 3 to 243 in the TLI-CsA/MPd-treated group. The titers fell within 24-48 hr after renal transplantation, to 3 to 81 in the untreated sensitized dogs; they were 3 to 9 in the TLI-ATG-treated group, and were 9 to 243 in the TLI-CsA/MPd treated group. The cytotoxic antibody titers reached postoperative peaks of 6500 to 200,000 in the untreated dogs; 729 to 6500 in the TLI-ATG-treated dogs, and 243 to 6500 in the TLI-CsA/MPd-treated recipients. The combined use of TLI and CsA/MPd can significantly inhibit the capacity of immunized recipients to muster a secondary humoral response to the DLA antigen(s) used in the sensitization process; such treatment also abrogates the ability of the recipients to reject renal allografts bearing the same DLA specificities in accelerated fashion. This effect of TLI and cyclosporine may be of relevance to current severe problems in high-risk hyperimmunized human renal transplant candidates.

Animals↗