[Pathology of the damaged kidney (and the use of plasma expanders)].
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Significant economic and medical drawbacks attend the requirement for infusion of large quantities of exogenous substitution fluid during therapeutic plasma exchange. A variety of physicochemical processes are available for the fractionation of plasma (ultrafiltration, fractional precipitation, adsorption, electrophoresis, selective enzymatic degradation) and we review here their application to 'closed loop' apheresis, a format in which the patient's own plasma is returned after the pathogenic species are removed. The different separation processes vary significantly in their method of action, their specificity, and their status of development. Disposables and hardware for two specific protocols, cascade filtration and cryofiltration, are already commercially available and appropriate for routine clinical use in limited subsets of diseases considered treatable by therapeutic apheresis.
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Following exposure to calcium ionophore A23187, washed peripheral blood mononuclear cells (MNC) aggregated and formed thromboxane, like platelets. However, while aspirin strongly inhibited platelet aggregation and thromboxane formation, it had a little effect on the aggregation of MNC. In about 50% of the samples studied, aggregation of MNC was associated with the secretion of ATP. However studies in which exogenous ATP or ADP were used, suggested that the aggregation of MNC is independent of the secretion of nucleotides. MNC from 2 thrombasthenic patients failed to aggregate and bound 9-10 fold less radiolabelled fibrinogen than those from normals when challenged with A23187. However, fibrinogen, which plays a major role in the aggregation of platelets, did not appear to be involved in the aggregation of MNC. A differing behavior of these two types of cells was also found when the effect of plasma was studied on the aggregation response to A23187. Indeed, citrated plasma greatly enhanced the aggregation of platelets while it suppressed the response to MNC. This inhibitory effect of plasma was not detected when heparinized plasma was substituted for citrated plasma. We conclude that the aggregation of MNC in response to A23187 does not involve basic events known to play a major role in the aggregation of platelets. The response to A23187 may be an important probe for understanding basic mechanisms and pathophysiological significance of the aggregation of MNC.
Plasma obtained from patients with MCNS in active stage suppressed the 3H-TdR incorporation of autologous or homologous lymphocytes stimulated with PHA-P and E rosette formation, while plasma from patients in remission did not. The depressed mitogenic response of lymphocytes from patients in the active stage significantly improved when the patient's plasma was substituted for the plasma from inactive MCNS or healthy persons and fetal calf serum. In the preliminary experiment, it was seen that the inhibitory factors were heat stable at 56 degrees C, unadsorbable to charcoal powder and retained in both the permeable and impermeable fractions of collodion bag.
BACKGROUND: It has been recently recognized that long-term infusions of hydroxyethyl starch (HES) as a substitute of human plasma may lead to deposits within the human skin and clinically induces severe pruritus in approximately one-third of the patients treated. OBJECTIVE: To analyze the clinical features and pathophysiology of HES-induced itching. METHODS: Clinical data of 86 patients were analyzed retrospectively. Furthermore, 10 patients were followed prospectively, in whom we also performed routine laboratory tests, skin biopsies, allergological investigations (skin prick, basophil degranulation test), and substance P measurements in stimulated macrophages. RESULTS: Special features of HES-induced pruritus included long latency of onset and persistence. Noteworthy, itching is not always generalized. 30% of patients present with localized pruritus. Symptoms were not relieved by antihistaminics. Accordingly, the basophil degranulation test after HES exposure was negative. Also, substance P release from macrophages was not increased following HES stimulation. Deposits were found mainly in macrophages and endothelial cells. CONCLUSIONS: Our findings indicate that pruritus in HES-infused patients is most likely not triggered by pruritogenic mediators. We support data from the recent literature, suggesting a direct stimulation of cutaneous nerves by HES deposits. In patients suffering from long-standing itching it seems important to consider previous HES exposure as a possible cause not only in generalized pruritus but also in localized symptoms.
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A synthetic polymer, Duxon, was developed and tested as a substitute of blood plasma for transfusion purposes. Tests of this preparation included a test for its influence on the haemopoietic stem cells and the graft-versus-host reaction (GVHR). A single dose or repeated doses of Duxon did not reduce the number of pluripotent haemopoietic colonies (CFU-S) in mice and short-term incubation of cells from haemopoietic organs of mice with Duxon resulted in a slight, yet significant, increase in the number of CFU-S. Injection of Duxon non-significantly diminished the manifestations of the regional GVHR. Incubation of spleen cells with Duxon significantly reduced their GVH reactivity in the regional test. The systemic GVHR was moderately inhibited by repeated doses of Duxon in sublethally irradiated mice. A significant delay in deaths of animals from GVHR was seen in lethally irradiated mice receiving a single dose of Duxon on day 4 after GVHR induction. Survival of lethally and sublethally irradiated mice was prolonged following injection of cells incubated with Duxon. Possible uses of Duxon, a preparation with mild immunosuppressive properties, not impairing haemopoiesis, are discussed.
Poly N-(2-hydroxypropyl)methacrylamide (Duxon) was studied as a substitute of blood plasma and was found to prolong significantly the survival of semiallogeneic skin grafts in mice and rats and to reduce MLC reactions of human lymphocytes. It did not inhibit the growth of lymphocytes and the growth of the fibroblast-like (diploid) or epithelioid (heteroploid) cell lines in tissue culture.
In the plasma separation simultaneously with the filtering off of patients' plasma a substitution solution is infused. A part of this substitution solution is also filtered off in the sequel. Therefore the volume measured of the filtered plasma only partly consists of the original plasma of the patient. The exact size of this part is calculated by the authors from the globulin concentrations in the patients' plasma before and after the plasma separation. In this case they proceed from the prerequisites that albumin is used as substitution solution and that the plasma volume remains constant during the plasma separation.