Results of partial liver transplantation in Finland.
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Biomedical subjects
Publications and source records attributed to H Isoniemi.
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The histological changes in renal allografts are usually studied when graft function has already deteriorated. The early results of renal allografts have improved dramatically during the last two decades, but the half-life of renal cadaveric allografts has remained unchanged at approximately 7 years. The mechanism of chronic rejection, and how to prevent it, is not known. We studied the histology of renal allografts under four different immunosuppressive regimens 2 years after transplantation. The aim of this study was to investigate whether histopathological changes exist in the renal allografts with relatively good and stable graft function. We also investigated whether there were differences in allograft histology between four immunosuppressive treatment groups 2 years after transplantation.
We analyzed the expression of class II antigens on graft tubular cells and the expression of IL-2R on lymphoid cells in 314 prospective aspiration biopsies taken from 30 consecutive patients with histologically verified acute vascular rejection (AVR). Based on histology, two main groups were seen: 11 grafts had features of AVR only and 19 grafts had a combination of AVR and acute cellular rejection (ACR). The AVR findings were also predominant in the latter group. In the grafts with a combination of AVR and ACR, patterns similar to ordinary ACR were seen in class II and IL-2R expression. On the contrary, no class II or IL-2R induction could be seen in the grafts with pure AVR and irreversible rejection. This pattern, demonstrated by immunocytology, suggested that AVR is a heterogenous group of rejections, where different cellular and molecular mechanisms are operating. Humoral mechanisms might be involved in these rejections.
Forty-five kidney transplant recipients with delayed onset of diuresis due to acute tubular necrosis (ATN) were examined with duplex ultrasonography (DU). Resistive index (RI) was measured on the 4th post-transplant day. Eleven grafts (24%) developed acute rejection. Mean RI prior to rejection of the 4th postoperative day in these grafts was 0.97 and in the 34 grafts which did not develop rejection mean RI was 0.82. There were 2/26 rejections (8%) in the group of grafts with an initial RI below 0.9 and 9/19 rejections (47%) in the group of grafts with RI of 0.9 or above on the 4th post-transplant day. Six months postoperatively there were 2/26 nonfunctioning grafts in the group with lower initial RI values (less than 0.9) and 6/19 nonfunctioning grafts in the group with higher indices (greater than or equal to 0.9). In nonfunctioning grafts a high initial RI (greater than or equal to 0.9) indicates that these grafts will be prone to developing acute rejection.
The induction of HLA class II antigens on graft tubular cells and IL-2 receptor expression on the infiltrating lymphoid cells was studied in 245 prospective aspiration biopsies taken during the first posttransplant month from 20 human renal allografts with histologically verified acute vascular rejection (AVR). Based on the histological findings, the specimens were categorized into two main groups: biopsies from grafts with features of AVR only, and biopsies with a combination of AVR and acute cellular rejection (ACR). Also in the second group the AVR findings were predominant. Biopsies were further divided into two subgroups, depending on whether the rejection was reversible or irreversible. Evaluation of class II and IL-2R expression was done by indirect immunoperoxidase staining using monoclonal antibodies. The initial posttransplant tubular cell class II expression was low in all 20 grafts, with 5-15% positive tubular cells, and IL-2R expression was negative. All 13 grafts with a combination of AVR and ACR displayed class II induction, closely correlating to the blast response, with 50% positive tubular cells on days 2-7 after the onset of rejection, and declining thereafter back to prerejection level in grafts with reversible rejection. In grafts with irreversible rejection, tubular cell class II expression remained elevated. A similar pattern was observed with regard to IL-2R expression: the IL-2R positive cells disappeared from the grafts with reversible rejection, but they persisted in the irreversible rejections. The same pattern of class II and IL-2R expression was observed in grafts with pure AVR and reversible rejection. Instead, completely different findings were seen in grafts with pure AVR and irreversible rejection: there was neither class II induction on tubular cells nor IL-2R expression on lymphoid cells. The persistant inflammation was dominated by mononuclear phagocytes, and no blast response could be detected during the entire follow-up. These findings demonstrate a close relationship between IL-2R expression and tubular cell class II induction also in AVR, in the majority of cases. On the other hand, the findings in grafts with pure AVR in histology and irreversible rejection suggest that AVR is a heterogenous group of rejections, where different cellular and molecular mechanisms are operating.
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A prospective randomized trial was carried out to compare the long-term effects of triple therapy based on low-dose cyclosporin A (CyA), low-dose methylprednisolone (MP) and azathioprine (Aza) with three different double drug immunosuppressive regimens. After initial triple drug immunosuppression for 10 weeks, 128 patients were randomized into four different immunosuppressive groups: one group continued with triple therapy (group A) and the three other groups were treated with different combinations of two drugs: Aza and CyA (group B), Aza and MP (group C) and CyA and MP (group D). This report presents the 2-year results. For groups A, B, C and D, graft survivals were 75%, 78%, 84% and 81%, respectively, and patient survivals were 84%, 84%, 84% and 94%, respectively. After 2 years no patient had returned to dialysis in group C compared with one to three patients in every CyA-using group. However, at the end of the 2nd year, group C included more patients with deteriorating graft function than the other groups. Median serum creatinine was 107, 120, 139 and 129 mumol/l for groups A, B, C and D, respectively. For the patients who remained on the original randomized protocol, there were no significant differences in graft function tests between the four groups, the median creatinine being 115, 115, 118 and 113 mumol/l for groups A, B, C and D, respectively. Thus, no graft deterioration had occurred during the 2 years for these patients following the original protocol.(ABSTRACT TRUNCATED AT 250 WORDS)
The association of an early steroid-resistant rejection (SRR) with HLA-DR antigens was analyzed in 410 kidney transplantations. A severe SRR leading to a poor (45%) 1-year graft survival (GS) occurred in 22 transplantations (5%). An acute reversible rejection (ARR) with a GS of 94% was found in 80 transplantations (20%). For the 308 (75%) transplantations with no early rejection episodes the GS was 91%. HLA-DR5 and -DR8 present in the donor as incompatible antigens were strongly associated with SRR. Further, a mismatched DR1 from the kidney donor predicted a rejection, either reversible or irreversible. These findings may have practical implications for an early diagnosis of SRR and for considering of rescue therapy whenever transplantation with disparities in these loci has been performed.