HLA-A, B matching of pretransplant blood transfusion is associated with poor graft survival.
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Biomedical subjects
Publications and source records attributed to W Land.
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In the last four years 125 renal transplantations were performed at the Transplantation Center in Munich. The mortality rate after transplantation could be lowered to below 10% in the first year; on the other hand the rate of loss of transplants observed in the Center was 40% in the same period. After mentioning the individual surgical complications following renal transplantation with reference to our own patients. The effect of blood transfusions on the survival time of the transplant is dealt with. It was found that transplant survival rate increased with the rise in the number of blood transfusions before the transplantation.
Women with uremia are usually infertile. Following successful renal transplants ovarian function resumes and conception becomes possible. Two cases of pregnancy following renal transplants are reported. The first patient had a Caesarean section at 33 weeks gestation for maternal indications, the second patient had a Caesarean section at 36 weeks gestation because of premature spontaneous rupture of the membranes. Both mothers and infants are in satisfactory condition. The problems of pregnancies following renal transplants are discussed and the literature since 1963 is reviewed. Pregnancy following renal transplantation is a high risk pregnancy for both the mother and the fetus. These high risks are acceptable if close supervision of the pregnancy by the nephrologist, gynaecologist and paediatrician are possible and if co-operation of the mother is satisfactory.
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In 60 patients with a kidney transplant 86 perfusion studies with 99mTc-DTPA were performed during the early postoperative period. Correlative data and clinical differentiation were obtained by isotope nephrograms, laboratory values and clinical presentation. In addition to evaluation of scintiphotos, time-activity curves were derived from the transplant and evaluated quantitatively, obtaining a perfusion ratio by a computer program. A ratio of greater than 0.80 was found to be normal. In 20 patients with acute rejection, the ratio was decreased. In 13 patients with acute tubular necrosis, the perfusion ratio was between 0.39 and 0.65, decreasing further during an added rejection crisis. Follow-up examinations confirmed rejection through a decrease of the perfusion ratio (mean difference 0.44; p less than 0.025). In 9 cases, successful rejection therapy was documented by an increase (mean difference 0.29; p less than 0.005). In addition to quantitative evaluation, visual analysis revealed acute occlusion of the renal artery, renal infarction, urinoma, ureteral stenosis or necrosis. Quantitative scintigraphy with 99mTc-DTPA broadened the methods of describing kidney transplant function. Its quantitative evaluation enables the definition of acute rejection and its differentiation from acute tubular necrosis combined with acute rejection in the early postoperative period. Since the method recognizes morphological alterations as well, it usefully complements isotope nephrography.
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In HR, primarily humoral immunologic factors trigger a sequence of events that finally destroys the transplanted organ. Unspecific trapping of WBC diminishes the RBF, especially in the first compartment--the cortex. Pretreatment with ALG is able to suppress this cellular participation partially, thus postponing the stop of RBF without preventing the influence of humoral factors on the graft. As shown by pathologic and functional criteria recorded for 8 hr, an exclusive measurement of total RBF does not reflect an inhibition of the course of HR.
A balanced combination of immunosuppressive regimens like cortisone, azathioprine and ALG can not only reduce the frequency, but also the severity of rejection episodes in kidney transplant patients. Addition of ALG influences the lymphocyte populations, especially T-lymphocytes. The significant reduction produced obviously includes cytotoxic effector lymphocytes as well as socalled regulator cells (suppressor cells). It seems as if this beneficial function for the graft is not only reduced under immunosuppressive therapy and administration of ALG, but disappears during rejection crises. The results indicate, however, that these cell populations recover quickly after finishing the immunosuppressive regimen.
In 20 patients treated with antilymphocyte horse gamma-globulin (ALG) the immune response was tested by means of the antigen elimination technique before, during and after ALG-therapy. The comparison of this method with agargel diffusion test, indirect hemagglutination and skin tests showed that immunization of patients against horse protein is indicated earlier and more reliable with the antigen elimination. Therefore this technique should be utilized during a therapy with foreign proteins especially when the results of other immunological test methods are insufficient.
Xenotransplantation in distantly related donor-recipient systems is rejected within minutes. According to present theories, hyperacute rejection is due to preformed antibodies. However, our results suggest that a nonimmunologic reaction plays a dominant role in the hyperacute rejection reaction. To analyze the hyperacute rejection reaction, a previously described model of isolated in vitro xenohemoperfusion was used in which rat kidneys were perfused with dog blood at constant pressure. Rejection criterion was cessation of xenograft perfusion flow rate with constant perfusion pressure and histologic findings of aggregation of thrombocytes and endothelial lesions. In our experimental approach, the donor kidney was perfused with separate cellular and humoral components of the recipient blood with redetection of the rejection activity in one of the recipient blood components. Each blood component was tested for preformed antibody before hemoperfusion. In control studies, xenoperfusion of rat kidneys with whole blood from the dog always resulted in hyperacute rejection. In contrast, allogenic perfusion with whole blood caused no rejection. In three groups, typical hyperacute rejection occurred. Perfusion with whole blood from newborn dogs; no preformed antibodies in vitro; perfusion with reactivated dog whole blood containing no preformed xenohemoagglutinating antibodies, which had been eliminated by adsorption, and perfusion with reactivated dog whole blood containing no preformed xenocomplement fixing antibodies also eliminated by adsorption, all resulted in hyperacute rejection. Whole blood from newborn dogs and reactivated, adsorbed antibody-free whole blood from dogs contained active complement. Perfusion of rat kidneys with heat decomplemented, antibody-containing or antibody-free dog blood showed no hyperacute rejection reaction. The addition of fresh complement to these last two groups resulted in typical hyperacute rejection.
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The purpose of this paper is to test serum factors which are by interaction with cells responsible for the HXAR. Special stress was laid upon the examination of different serum fractions with or without the presence of preformed natural antibodies. Xenohemoperfusion: Rat kidneys were isolated and perfused in vitro with both whole blood resp. serum fractions and various perpheral cells of dogs. Rejection criterion was the diminishing renal blood flow at a constant pressure of the perfusion. Perfusate: Dog serum fractions were isolated by means of carton electrophoresis into the following fractions: Albumin, alpha-1, alpha-2, beta and gamma-globulin. Dog peripheral blood cells were separated into WBC, RBC and platelets by means of centrifugation and washing of EDTA whole blood. The serum fractions were tested for antibodies using hemagglutination and complement fixation techniques. 1. Hemoperfusion with serum fractions leads to a longer perfusion rate and to higher renal blood flow than perfusion with whole dog blood. 2. No preformed natural antibodies were found in the alpha-2 globulin fractions; however, perfusion with alpha-2 globulin fractions produced a rejection phenomenon both in combination with cells and erythrocytes. 3. Perfusion with serum fractions containing preformed natural antibodies produced a rejection only when WBC and thrombocytes were present. These results suggest that HXAR is induced by two different mechanisms: 1. The effect of humoral natural antibodies (found in the beta and gamma globulin fraction) together with peripheral cells. 2. The effect of a non-immunological humoral factor, found in the alpha-2 globulin fraction, leading to destruction of the xenogeneic organ, obviously to a minor degree dependent on interaction with peripheral cells.
Rat kidneys (donor organs) were perfused in an in-vitro perfusion circuit using blood or modified blood from the dog (recipient). Hyperacute xenogeneic rejection (HXR) in widely divergent species system could even be seen, when preformed natural antibodies were absent. These data presented suggest that this form of HXR is at least partially induced by nonspecific (equals nonimmunologic complement activation, followed by complement mediated disease (liberation of vasoactive and other substances leading to increased permeability. e. g. Anaphylatoxin) of the donor kidneys.
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