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Biomedical subjects

S Jensik

Publications and source records attributed to S Jensik.

13 recordsLinked to original sources

Use of collagen injections for vesicoureteral reflux in transplanted kidneys.

Reports in the literature suggest the incidence of vesicoureteral reflux (VUR) in transplanted kidneys to range from 2-79%. Collagen injections have been used with reported success rates of up to 65% to prevent VUR into native orifices in children, but have not been studied in transplant neo-orifices. We evaluated the use of collagen injections in seven patients with transplant kidney neo-orifices who displayed grades II-IV VUR and seemed to be related to symptomatic urinary tract infections (UTIs). Postoperative VCUGs obtained at 2 months showed improvement in the grade of reflux in four of seven (57.1%) patients; one (14.3%), no change; and two (28.6%), worse reflux. All patients also redeveloped symptomatic UTIs after collagen injection. We conclude that the use of collagen injections in kidney transplant neo-orifices did not prevent VUR. Although prevention of VUR may have been achieved short term, VCUG examinations 2 months after initial injection revealed persistent reflux. Etiologies for failure to prevent VUR may be the readily absorbable nature of collagen, technical aspects of the procedure, the degree of reflux, and anatomic differences between native orifices (which lie on a well-supported trigone) and transplant neo-orifices (which lie on the posterior wall with less support).

Collagen↗

Histological characterization and pharmacological control of chronic rejection in xenogeneic and allogeneic heart transplantation.

BACKGROUND: Chronic allograft rejection remains a major barrier to successful long-term allograft transplantation in humans. Chronic allograft rejection is characterized by the appearance of arterial lesions with concentric intimal thickening. This study investigates the development and control of chronic rejection in hamster cardiac xenografts transplanted into Lewis rats. METHODS: Chronic rejection in the xenograft model involves transplantation of hamster hearts into Lewis rats treated with leflunomide (Lef) continuously at 15 mg/kg/day. The allograft model involves transplantation of Lewis hearts into Fisher-334 rats treated with cyclosporine (CsA) at 2.5 mg/kg for 5 days. RESULTS: The average scores of arterial intimal thickening on day 45 after transplantation were 1.89+/-0.43 in the xenograft and 2.50+/-0.72 in the allograft. The basic pathology of both xenografts and allografts undergoing chronic rejection was arterial intimal thickening comprising smooth muscle cell proliferation, mononuclear cell infiltration, and fibrosis. The majority of cells infiltrating the arterial intima and myocardium were T cells and macrophages. Compared with the allograft, intimal edema, matrix deposition and fibrinoid necrosis were specifically presented in the xenografts and generally involved the larger arteries. The predominant isotype of antibody deposited was IgM in xenografts and IgG in allografts. When combined Lef and CsA therapy was initiated on day 45 after transplantation, the changes of chronic rejection were reversed in both xenografts and allografts by day 90. The scores of intimal thickening were significantly reduced to 0.97+/-0.45 and 1.48+/-0.56, respectively. CONCLUSIONS: We conclude that chronic rejection can be induced in xenografts under conditions of inadequate immunosuppression. Chronic rejection in xenografts involves arterial lesions that bear some histological similarities to, as well as differences from, those observed in chronically rejected allografts. Finally, combination therapy with CsA and Lef reduced the incidence and severity of the intimal lesions in both chronically rejecting xenografts and allografts.

Animals↗

Ultraviolet-B irradiation of leukapheresis. Products: dose-response relationship with the mixed lymphocyte reaction.

Ultraviolet-B (UVB) irradiation of blood constituents intensifies their anti-rejection effect in pretransplant donor-specific transfusions. UVB-induced inhibition of the mixed lymphocyte reaction (MLR) between UVB-irradiated donor cells and prospective recipient cells is a predicator of this anti-rejection effect. In order to define the dose-response relationship between the incident UVB irradiation on leukocyte concentrates and subsequent inhibition of their MLR responses, we collected 4 +/- 2 x 10(9) leukocytes (93 +/- 7% lymphocytes) in 200 ml plasma from each of three volunteers by leukapheresis and exposed them to rapid, serial doses of UVB irradiation which was delivered by a blood product irradiator (4R4440 UVB Irradiator, Baxter, Inc) with aliquots removed between doses. Lymphocytes from each aliquot were placed in MLR with panel donors and studied in three groups: 1) the panel donor cells were gamma-irradiated (1,500 rads) (i.e., only the UVB-irradiated cells could proliferate), 2) the UVB-irradiated cells were gamma-irradiated (i.e., only the panel lymphocytes could proliferate), and 3) no gamma-irradiation (i.e., both cell populations could proliferate). Each group had a similar UVB dose-related diminution in the MLR (p = .79, ANOVA). A single dose of 6 J/cm2 extinguished the MLR to baseline in all groups. This dose should theoretically prevent transfused cells from producing either graft-versus-host disease or allosensitization, and might heighten their tolerogenic effect. This dose will be employed in our study of donor-specific leukocyte transfusion in clinical renal transplantation.

Dose-Response Relationship, Radiation↗

Pharmacologically induced regression of chronic transplant rejection.

Chronic rejection, characterized by a progressive obliterative arteriopathy, is a major cause of graft failure in long-surviving human transplants for which there is no effective treatment. Leflunomide, an isoxazol derivative, has been shown to be a novel immunomodulatory drug that profoundly suppresses the immune response. In this study, 58 Fisher-344 rats received cardiac transplantation from Lewis rats. All the recipients were given CsA at 2.5 mg/kg for 5 days postoperatively. Without further treatments, the arterial intima was progressively injured by mononuclear cell infiltration and Ab deposition. Smooth muscle cell and fibroblast proliferation in the intima became a predominant phenomenon by day 90. CsA was ineffective in controlling the progress of arterial intimal thickening when treatment began on day 30. Leflunomide at 5 mg/kg failed to control arterial intimal thickening by day 60 when therapy began on day 30. However, the progress of arterial intimal thickening was significantly inhibited by day 90 when the dosage of leflunomide had been increased to 10 mg/kg on day 60. Combined therapy with leflunomide and CsA at 5 mg/kg for 30 days dramatically reversed the arterial thickening by day 60. After increasing the dosages of both leflunomide and CsA to 10 mg/kg on day 60, the combination therapy steadily controlled the chronic rejection. Only the combination therapy significantly down-regulated circulating antidonor IgM and IgG titers. In rat smooth muscle cell culture, this same drug combination had a synergistic inhibitory effect on proliferation. Therefore, the combination therapy of leflunomide and CsA could reverse and control the progress of chronic rejection, while leflunomide, at higher dosage as a monotherapy, could stabilize chronic rejection in this model. The mechanism of the regression of chronic rejection by leflunomide and cyclosporine may be related to their in vitro abilities to control not only lymphocyte but smooth muscle cell proliferation, as well. The synergistic effect of these two drugs on vascular smooth muscle cell proliferation in vitro may be an important part of this novel activity. This unique feature holds intriguing possibilities for treating established chronic rejection.

Animals↗

Amputations associated with arteriovenous access.

This study was performed to investigate the common characteristics of hemodialysis patients who need upper limb amputations. An index case was identified and involved questioning physicians and reviewing hospital and office records. Hemodialysis patients who have diabetes and leg amputations are at high risk for ischemic episodes that may lead to amputation of the arm, distal to the arteriovenous access site.

Adult↗