Increased risk of malignancy and blood-membrane interactions in uraemic patients.
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Biomedical subjects
Publications and source records attributed to E Kinugasa.
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Nafamostat mesilate (NM), an ultrashort-acting multi-enzymatic inhibitor, is a useful anti-coagulant in high bleeding risk patients needing hemodialysis. We applied NM as a membrane plasmapheresis (MP) anti-coagulant in patients with high bleeding risk. Eleven patients, the majority with hepatic failure and active hemorrhagic foci or severe bleeding diathesis, could be treated with MP 22 times under anti-coagulation by 20-40 mg/h/NM by continuous infusion without any trouble. Celite-activated coagulation time (CCT) at the plasma separator inlet and outlet was adequately prolonged during MP, but CCT in systemic blood showed no prolongation throughout the procedure, because NM was rapidly inactivated. There was no observable blood coagulation in the extracorporeal circuit including the plasma separator. No adverse reaction or exacerbation of hemorrhage was noted throughout the MP. NM thus appears to be a useful and safe anti-coagulant not only for hemodialysis but also for MP in high bleeding risk patients.
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To clarify the effects of correction of anemia with recombinant human erythropoietin (r-HuEPO) on the hemostatic defects in uremia, hemostatic parameters were examined in 18 hemodialysis patients with renal anemia. Anemia improved significantly 12 weeks after r-HuEPO therapy (stage II) compared to pretreatment (stage I) and 6 weeks discontinuation (stage III) periods. Platelet count did not change among the three stages, however, mean platelet volume increased significantly at stage II in comparison with stage I. Ivy bleeding time (BT) significantly shortened at stage II and prolonged again at stage III. Although there were no significant changes in platelet aggregation, plasma TxB2, 6-keto-PGF1 alpha, F.VIII:C and F.VIII:Ag levels throughout the study, platelet adhesion and von Willebrand factor (vWf):Ag significantly increased at stages II and III. Augmentations in these parameters were more remarkable in BT-shortened patients (n = 12) than in the BT-unchanged group. These results indicate that correction of anemia with r-HuEPO brought about improvement in uremic hemostatic defect via the increase in red cell volume and vWf:Ag, and new production of platelets, reflected by the improvement in platelet adhesion.
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To evaluate the effects of correction of anemia with recombinant human erythropoietin (r-HuEPO) on the hemostatic defects in uremia, hemostatic parameters were examined in 18 patients with renal anemia receiving hemodialysis (HD). During the study, hematocrit (Ht) increased from 22.9 +/- 3.1% (mean +/- SD) at pre-treatment (stage-I) to 31.0 +/- 3.0% 12 weeks after 3000 IU intravenous r-HuEPO administration at the end of every HD (stage-II), and decreased to 26.2 +/- 4.2% 6 weeks after r-HuEPO discontinuation (stage III). Platelet count did not change among these three stages, however, mean platelet volume significantly increased at stage II compared to stage I. Ivy bleeding time (Ivy-BT) significantly shortened at stage II (I; 14.3 +/- 6.0, II; 10.1 +/- 6.5 min, p less than 0.01), and prolonged again at stage III (p less than 0.05 vs stage II). Among the patients, 6 out of 18 patients did not show any reduction in Ivy-BT (unchanged group). Though there were no significant changes in platelet aggregation rates, plasma TxB2, 6-keto-PGF1 alpha, F. VIII: C, and F. VIII: Ag levels throughout the study, platelet adhesion rate was significantly improved at stage II (I; 11.8 +/- 6.8, II; 19.6 +/- 12.8%, p less than 0.05), and similar augmentation in vWf: Ag was observed. Improvement in these two parameters were more remarkable in shortened Ivy-BT group (n = 12) than in unchanged group.(ABSTRACT TRUNCATED AT 250 WORDS)
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Several lines of evidence suggest that beta 2-microglobulin (beta 2M) accumulation in long-term hemodialysis (HD) patients results in so-called dialysis-associated amyloidosis (DAA), which is clinically manifested by carpal tunnel syndrome, osteoarthropathy, and the other organ involvements. For the purpose of preventing the beta 2M accumulation, the efficiency of beta 2M removal during (HPM), hemofiltration (HF), HD, and charcoal hemodiafiltration (HDF) with high-performance membranes (HPM), hemofiltration (HF), HD, and charcoal hemoperfusion was evaluated. Among 27 patients treated with these methods, significant beta 2M removal was noted in HDF with HPM and HD with polyacrylonitril (PAN) membrane. However, treatment of HDF with HPM for more than 6 months caused no remarkable improvement in clinical symptoms of patients, and serum beta 2M levels decreased in only two out of 15 patients. These results imply that beta 2M might be most effectively removed by HDF with HPM and HD with PAN membrane, but further long-term studies will be necessary to conclude whether these procedures could become successful therapeutic regimen for DAA.
The phagocytic activity of polymorphonuclear leucocytes (PMN) in 57 patients with IgA nephropathy was investigated using Immunobeads. Depressed activity was detected in 41 patients (72%). A significant correlation existed between the ingestive function of neutrophils and glomerular histological abnormalities, such as the degree of mesangial proliferation. In addition, 25 patients with IgA nephropathy were studied to detect the presence of immunological inclusions in the PMN by a direct immunofluorescent technique (anti-IgG, IgA, IgM and C3). Intracytoplasmic inclusions containing IgA were frequently detected in the PMN, and a negative correlation was found between the percentage of IgA-positive PMN and the phagocytic activity of neutrophils in patients with IgA nephropathy. These results suggest that the activity of neutrophils represents one of the important factors in the pathogenesis of IgA nephropathy and that mesangial IgA deposition is partly caused by decreased clearance activity of PMN.
Dialytic performance and biocompatibility of a newly developed cellulose triacetate (CTA) membrane with a microgradient porous structure, produced without using polyvinylpyrrolidone (PVP) and liquid paraffin, were compared with those of a conventional polysulfone (PS) membrane dialyzer. In vitro and clinical results demonstrated no significant difference in the dialytic performance and biocompatibility of the two dialyzers, but the CTA dialyzer lost less albumin during dialysis than the PS. These results suggest that a CTA membrane dialyzer with a porous microgradient structure attained comparable performance and biocompatibility to PS, and the risk of albumin loss was suppressed by the new CTA membrane.
To clarify the roles of endothelin (ET: vasoconstrictor) and platelet activating factor (PAF: vasodilator) in hemodialysis (HD), intradialytic changes in those substances were compared by a crossover study between HD with regenerated cellulose (RC) and polymethylmethacrylate (PMMA) membranes using currently developed radioimmunoassay methods. Hemodialysis patients demonstrated higher plasma ET values than normal controls, and hypertensive HD cases showed the highest levels. Although ET decreased significantly during the initial stage of HD with both membranes, the decreasing rates were greater in the group with intradialytic hypotension than those in the normotensive group. Plasma PAF did not differ among normal controls, hypertensive HD, and normotensive HD patients. Platelet activating factor tended to increase during HD in both hypotensive and normotensive groups; however, the increasing rates were greater in HD with RC than those with PMMA. These results indicate that the decrease in ET may partially contribute to the initiation of HD induced hypotension. Because PAF is an intracellular mediator, and there is an intradialytic increase in PAF with RC membrane, PAF should be regarded as one of the indices of membrane biocompatibility.
The effects of recombinant human erythropoietin (rHuEPO) on endothelial vasoactive substances were evaluated in 19 regular hemodialysis patients. Blood cell counts, plasma endothelin (ET), alpha-human atrial natriuretic peptide (ANP), platelet activating factor (PAF), 6-keto-prostaglandin F1 alpha (PGF1 alpha), and 11-dehydro-thromboxane B2 (TXB2) were evaluated before rHuEPO treatment; at 4, 8, and 12 weeks during treatment; and 5 weeks after the end of treatment. PAF and TXB2 remained unchanged during the study period, PGF1 alpha and ET significantly increased, and ANP decreased along with an improvement in the anemia. Since endothelial vasoactive substances changed significantly during rHuEPO therapy, the correction of anemia with rHuEPO may affect endothelium.
The biocompatibility and thrombogenicity of polyethylene-glycol (PEG)-grafted cellulose hemodialysis (HD) membranes (PEGC) were investigated in cross-over HD of five HD patients with ordinary cellulose (OC). The PEGC significantly suppressed transient leukocyte and thrombocytopenia, and release of C3a, beta-thromboglobulin and platelet factor 4, in corresponding with the quantity of grafted PEG. HD with PEGC resulted in lower granulocyte elastase production, protein and blood cells adsorption on the membrane surface than those with OC. Minimum heparin in HD with PEGC was three times lower than that with OC, with the thrombin-antithrombin III complex elevation lower than that in HD with OC. The results indicate that the grafted PEG effectively suppresses blood and membrane interaction, thus improving biocompatibility and reducing thrombogenicity in clinical HD.
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