Biomedical subjects
Publications and source records attributed to W Fassbinder.
A 46-year-old chemist inadvertently inhaled arsine (AsH3) at work. After several hours abdominal cramps, haemolytic jaundice and massive haemoglobinuria developed. There was transitory hypoxaemia and compensated renal insufficiency. After forced diuresis and transfusions the patient slowly recovered. The only residual defect is arterial hypertension which requires treatment.
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The influence of prospective HLA-DR matching on the graft survival rate was investigated in a multicenter analysis of 85 transplants. Simultaneously in a retrospective analysis of graft outcome the importance of matching for MT-antigens MT1, MT2 and MT3 as a newly defined B-cell alloantigen system was evaluated. HLA-DR antigens and MT-specificities were determined on B-cells enriched by nylon-wool filtration using locally well characterised HLA-DR antisera and the antiserum set of the 8th International Histocompatibility Workshop ("disease set") which allowed the definition of the HLA-DR specificities HLA-DR 1-9 and of the MT-antigens MT1-3. HLA-DR matching showed a significantly improved graft outcome only in HLA-DR identical donor-recipient combinations. In 11 of 60 patients with one HLA-DR compatibility additional matching for two MT-antigens, however, improved the two year graft survival rate from 60% to 91%. Altogether 17 patients were matched for two MT-specificities with their kidney donor and showed a superior prognosis of 94% at two years compared to 53% or 17% of recipients with one or zero MT compatibility. Graft outcome in this patient group was also superior to that of HLA-DR identical or HLA-AB identical grafts. These data suggested that the MT-system rather than the HLA-DR antigens may be of critical importance in cadaver kidney transplantation. In addition a favorable influence of pretransplant blood transfusions on less HLA-DR matched grafts was confirmed.
Anemia of endstage renal failure improves shortly after kidney transplantation. However, in about 10% of transplanted patients polycythemia occurs. By use of a sensitive in vitro bioassay the pathogenetic role of erythropoietin (Ep) was investigated in 12 patients with post-transplant erythrocytosis (PTE), and compared to 12 non-PTE patients. The mean Ep of 160 mU/ml was significantly elevated in patients with PTE as compared to 25 mU/ml of 36 healthy controls, whereas, the mean Ep of 24 mU/ml in non-PTE patients did not differ significantly from healthy controls. To further elucidate the mechanism of inappropriate Ep production, selective venous catheterization of native and transplanted kidneys was performed in six patients. In four PTE patients the mean Ep in native kidney veins of 110 mU/ml was significantly higher than the peripheral Ep of 66 mU/ml, whereas, mean Ep in kidney graft veins was 51 mU/ml. In contrast, in two non-PTE patients no significant difference between mean Ep from native and transplanted kidney veins was observed. We conclude that some patients escape from normal feedback regulation either due to autonomous Ep production or due to feedback regulation at an elevated level of hematocrit and that inappropriate Ep production originates from the diseased native kidneys.
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In 167 first cadaver kidney recipients and their donors the blood groups ABO, Rhesus, Lewis, MN, Ss, P, Kell and Duffy were determined. The influence of incompatibility in each system as well as of simultaneous presence of several mismatches was analysed. Whereas one-year graft survival of Lewis-compatible grafts was 67 per cent (p = 0.02). The other blood groups showed no significant effect on graft outcome. Cumulative red cell incompatibilities, however, led to decreased survival rates. One-year graft survival in the group with greater than or equal to 4 incompatibilities was only 51 per cent versus 69 per cent in transplants with less than 4 incompatibilities (18% difference, p less than 0.01). When the Lewis system was excluded from analysis, the difference in survival rates was reduced to only six per cent. These data indicate that cumulative incompatibilities of red cell antigens have an unfavourable effect on graft survival. Of the different blood groups, the Lewis system is of major importance.
Since 1980 we have treated in 14 patients 19 steroid resistant acute vascular rejection (AVR) episodes by plasma filtration (PF). Each episode was treated by six PF with 5L plasma being filtered and simultaneously replaced by 3.5 per cent Albumin-Ringer-lactate. After each PF 20g immunoglobulin (Intraglobin) was given intravenously. In all cases renal function improved following PF. In the long term one graft was lost due to chronic irreversible vascular rejection, all others are still functioning, nine of them six months and eight of them 12 months post PF treatment. They show no signs of rejection. PF with repletion of immunoglobulins after treatment is a simple and safe procedure, which in our hands proved to be quite effective in reversal of AVR.
The vast majority of grafts with acute vascular rejection (AVR) undergo irreversible loss of function, since this type of rejection usually does not respond to increased levels of immunosuppression. Since 1980 we have treated with plasmafiltration (PF) 14 steroid resistant episodes of AVR in 10 patients. In the treatment of each episode 6 X 5 L plasma were filtered and simultaneously replaced with 3.5% albumin-Ringer-lactate solution. After each PF, 20 g immunoglobulins (Intraglobin) were replaced i.v. In all cases following PF renal function improved. One graft was eventually lost as a result of chronic irreversible vascular rejection; all others are still functioning. Eight of the 10 patients have been observed now for at least 6 months since beginning PF treatment and 5 of these 8 have been followed for more than 12 months. None of them shows signs of rejection. PF with replacement of immunoglobulins after treatment appears to be a simple and safe procedure, which in our hands proved to be quite effective in reversing AVR.
We investigated in a prospective study the effects of perioperative blood transfusions on the outcome of renal transplantation. All patients (n = 105) receiving their first cadaveric renal allograft were transfused perioperatively (i.e. 0-6 hours before transplantation) with two units of non-washed, unfiltered packed red cells. Forty-eight were transfused perioperatively only; 57 patients had received blood earlier and thus were transfused pre- and perioperatively. Graft survival one and two years post-transplant was 79 per cent at both time intervals in the group transfused perioperatively only, and 85 per cent and 74 per cent in the pre- and peroperatively transfused group. No adverse effects were observed concerning perioperative transfusions. In patients transfused perioperatively only, acceptable graft survival rates are obtainable. In these patients the risk or presensitisation is avoided, and thus their chance of successful transplantation increased.
Conventional therapy of acute rejection is almost exclusively based on increased steroid dosage, however, a considerable number of grafts undergo irreversible steroid resistant rejection (SRR). We investigated in a prospective study the effects of antithymocyte globulin (ATG) and plasmafiltration (PF) in cases of SRR. Acute interstitial rejections were treated with ATG, acute vascular rejections with PF. Thirty-nine of 42 (93%) cases of SRR were reversed by these forms of therapy. In 68 recipients of first cadaveric renal allografts actuarial one year graft survival has improved to 88 (+/- 5) per cent since the introduction of ATG and PF for SRR. Severe side effects or increased mortality were not observed, none of the patients with either form of therapy died. Thus ATG and PF are valuable adjuncts in the treatment of SRR.
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The vast majority of grafts with acute vascular rejection (AVR) undergoes irreversible loss of function, since this type of rejection usually does not respond to increased immunosuppression. Since 1980 we have treated in 22 patients 27 steroid resistant AVR by plasmafiltration (PF). Per episode 6 x 5 L plasma were filtered and simultaneously replaced by 3.5% Albumin-Ringer-lactate. After each PF 20 g immunoglobulins (Intraglobin(R] was substituted i.v.. In all cases renal function improved following PF. In the long run 1 graft was lost due to chronic irreversible vascular rejection, in 2 patients rejection was not reversed by PF, all others are still functioning, 19 of them 6 months and 8 of them 12 months post PF treatment. They show no signs of rejection. PF with repletion of immunoglobulins after treatment is a simple and safe procedure, which in our hands proved to be quite effectful in reversal of AVR.
Changes in haematocrit of 29 haemodialysis patients were followed 12 months before, close to and 12 months after parathyroidectomy. Mean haematocrit decreased significantly from 31.6 +/- 8.6 per cent to 29.1 +/- 8.4 per cent and increased to 33.3 +/- 7.9 per cent after PTX. Serum erythropoietin concentration, investigated pre and 6-12 months post PTX, at a time, when an increase of haematocrit values had been observed, did not significantly change (63 +/- 58 vs 67 +/- 37 mU/ml). The effect of 1-84 bovine parathyroid hormone on erythropoiesis was studied in vitro. A dose-related inhibition of colony formation of both fetal mouse liver and human bone marrow erythroid cells was observed in the presence of two to 8U parathyroid hormone/ml, suggesting direct bone marrow toxicity by excessive parathyroid hormone concentrations.
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Between 1973 and 1981 23 transplantations of kidneys from living related donors have been performed in Frankfurt/Main. Donor complications were haematopneumothorax (1 case) and reversible urinary tract infections (3 cases). All donors were discharged after 8-12 days, all have until now (6 months to 8 years postoperatively) normal excretory renal function and normal arterial blood pressure. Patient-survival in the recipients is 5 years postoperatively 96% and graft-survival is 90%. Nine patients received HLA-identical kidneys, all have excellent to fair function of the grafts, 7 patients are off steroids. In 14 cases kidneys were transplanted, although donor and recipient shared only one haplotype. In these patients 5-year graft survival is 84%. Seven patients have normal graft function, whereas 6 patients have a reduced function or have rejected. One patient died. Results of kidney transplantation using living related donors are--even when donors with only one haplotype-identity are accepted--much better than those obtainable when using cadaveric donors. When renal transplantation is considered, patients should be informed about the favourable results attainable with kidneys from living related donors.