Development of selective albumin collection system by double filtration plasmapheresis.
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Biomedical subjects
Publications and source records attributed to K Era.
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Leukocyte kinesis in the capillary vascular bed during hemodialysis (HD) was investigated to elucidate the mechanism of transient leukopenia. Leukocyte movement was observed microscopically during HD using the rabbit ear chamber (REC) technique, which permits visualization of the movement of blood corpuscles in capillaries. Blood was drawn from the femoral artery and returned into the auricular and/or carotid artery so that the blood passing through the hollow fiber artificial kidney (HFAK) flowed into capillaries in the REC. Leukocyte counts of blood samples taken from the afferent and efferent limbs of the HD circuit, the right jugular vein and the right atrium were determined consecutively during HD. The difference in the leukocyte count was observed between the afferent and efferent limbs for the first 15 minutes and thereafter between the efferent limb and the jugular vein. The "transpulmonary" difference in the leukocyte count was not noticed throughout HD. Between 15 and 90 minutes after the start of HD, scarcely any circulating leukocytes were found in capillaries in the REC and some leukocytes were attached to the endothelial surface. Thereafter circulating leukocytes were seen again and detachment of leukocytes from the endothelial surface was observed. No leukocyte aggregation or embolization of aggregating leukocytes was noticed. This evidence suggests that leukopenia may be attributed to the transient shift of leukocytes to the marginal pool of the vessel lumen and this process may not be specific for the pulmonary vasculature, but may occur in the first capillary bed into which the blood passing through the HFAK flows.(ABSTRACT TRUNCATED AT 250 WORDS)
Several kinds of plasma fractionators have been introduced to actively separate protein fractions between albumin and globulins in double filtration plasmapheresis. However, relatively large molecular weight proteins are known to be partially trapped by the membrane in a plasma fractionator. In this paper, effects of membrane trapping on separation characteristics in plasma fractionators were examined during in vitro and in vivo studies. All in vitro experiments were done with a closed circuit under constant-flow rate filtration. Protein concentration in feed tank kept constant at no filtration in AS-14H, Evaflux 4A and 2A, while 20-40% of IgG and 40-60% of beta-lipoprotein in 2 liter plasma were removed by membrane trapping for 300 min when filtration fraction equaled 0.87. Protein plugging to the membrane seems to be a major factor in these proteins. And, Dead-end and Partially Discarded modalities with relatively high filtration fraction are effective for the separation between albumin and globulin. Twenty-seven DFPP treatments in 13 patients with autoimmune diseases were done to allow us to estimate the effects of membrane trapping during an in vivo study. All treatments using 6 types of plasma fractionator were performed under constant operating conditions with Partially Discarded modality. In any plasma fractionator, beta-lipoprotein was fairly trapped at 30 min after the start of treatment.
A new method for urea removal using a gas membrane is introduced along with some preliminary results. The membrane used was expanded polytetrafluoroethylene (E-PTFE) which is highly permeable to gaseous substances, while at the same time it is highly resistant to water permeation. In in vitro experiments using 10 mmol/L ammonia solution it was revealed that the single-pass reduction rate was approximately 95% at 30 degrees C at a flow rate of 200 ml/min. In animal experiments using four dogs, the extraction rate of urea was 40.4 +/- 4.4% after four hours of dialysis using 5 L dialysate. However, elevation of blood ammonia was observed in all dogs tested. Removal of ammonia by means of a gas membrane is considered to be feasible and has the possibility of being used for maintenance hemodialysis in combination with urease and charcoal.
Orally diluting hemofiltration (ODHF), herein reported, is a new technique where the body fluid is purified by cooperative procedures of dilution-supplementation with oral electrolyte solution and filtration using the RP-6 dialyzer. One uremic patient was maintained for two months on a five-hour, three-times-per-week ODHF schedule, and another patient was maintained for four months on the same regimen with no supportive hemodialysis.
Introduction of high flux-type dialyzers, such as the RP-6, makes it necessary to devise an ultrafiltration rate controller for a single pass system. For this purpose, a new pre-set ultrafiltration rate controller has been developed and examined experimentally and clinically. The controller has twin chambers, each of which is divided into two symmetrical parts by a vertically-placed diaphragm. The diaphragm shifts repeatedly from right to left, aspirating in and driving out fresh or used dialysate alternately. If one removes a certain amount of used dialysate from a branch of the efferent line, negative pressure develops and aspirates an equal amount of water from the dialyzer. Therefore, extra dialysate obtained by a pump precisely reflects ultrafiltration rate. The controller has been used on five patients. The scheduled ultrafiltration rate was easily obtainable. The apparatus is also available for hemodiafiltration. Initial clinical trial has been promising.
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Continuous recirculating peritoneal dialysis (CRPD) was newly introduced to improve solute removal efficiency in conventional dialysis therapies such as hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). In CRPD, a part of the dialysate in the peritoneal cavity was drained through a double-lumen catheter and purified by an extracorporeal dialyzer. Urea removal characteristics in CRPD were examined in a canine study. In this study, a recirculation-dialysis experiment using a dog weighing 9.0 kg was carried out under 100 and 200 ml/min of flow for recirculating and delivered dialysates, respectively. An FB-50H (Nipro Medical Industries, Ltd., Osaka, Japan) composed of cellulose diacetate membrane with 0.5 m2 of surface area and Dianeal-1.5 (Baxter Limited Laboratories, Tokyo, Japan) containing urea were used as the extracorporeal dialyzer and dialysate. Urea peritoneal and dialyzer dialysances (DBP and DBD) were 3.05 and 33.3 ml/min by computer simulation using a compartment model for CRPD. This DBP value can be estimated as 20.3 ml/min for a 60 kg human. From this result, time-averaged value for BUN over an 8 hr/day CRPD, combined with three exchanges/day as CAPD is estimated to be 34.3 mg/dl, which is much lower than 45.2 mg/dl for a 12 hr/week HD, or 53.0 mg/dl for conventional CAPD.
Non-heparin hemodialysis (HD) was successfully done in anuric dogs with the oral administration of a newly developed antiplatelet agent, 4-cyano-5,5-bis(4-methoxyphenyl)-4-pentenoic acid, (E5510, Eisai Pharmaceutical Co., Japan). In the current study, the antithrombotic effect of E5510 during HD was investigated. Eleven mongrel dogs with bilateral ureteral ligation were given 0.1 mg/kg of E5510 orally 1 hr before undergoing 4 hr HD using hollow fiber dialyzers, (PMMA 5, regenerated cellulose 6) without heparin and under general anesthesia. Blood samples were taken before the administration of E5510 and before and 1, 2, 3, and 4 hr after starting HD; blood counts, hematocrits, blood chemistries, and plasma thromboxane levels (TxB2) were examined. Platelet aggregation, activated clotting times (ACT), and activated partial thrombin times (APTT) were also measured, and sequential plasma E5510 concentrations were determined. In 10 of 11 anuric dogs, non-heparin HD was successfully done with minimal clotting in the dialyzer and drip chambers. The maximum aggregation rate was depressed to less than 20% of the initial value throughout HD. Plasma TxB2 concentration was depressed, and ACT and APTT were mildly, but not significantly prolonged. Neither hemorrhagic complications nor other side effects of E5510 were observed.
Several kinds of dialyzers, with highly permeable membranes (HPM), have been designed to specifically remove beta 2-microglobulin (BMG). To clarify their solute transport characteristics, nine types of HPM dialyzers were evaluated during in vivo and in vitro studies using human plasma and aqueous solutions. No BMG membrane adsorption and/or plugging was seen with cellulosic membrane dialyzers during in vitro experiments using human plasma. On the other hand, all synthetic polymer membrane dialyzers had adsorptive properties, and in a dialyzer with a polymethylmethacrylate membrane, a large amount of BMG was removed by adsorption alone. Dialyzers with cellulose triacetate and polyacrylonitril membranes showed higher values of BMG diffusive dialysance (greater than 20 ml/min) and sieving coefficient (greater than 0.9). From in vitro experiments using an aqueous solution containing several solutes with relatively small or middle molecular weights, all HPM dialyzers had a higher overall mass transfer coefficient than any conventional membrane dialyzer.
Change in the electrical charge of leukocyte surface membranes during hemodialysis (HD) using a cellulose membrane was studied by examining adsorbability of leukocytes taken from patients undergoing HD to cation and anion exchange resins. Leukocytes of HD patients were well adsorbed to both anion and cation exchange resins, whereas normal leukocytes were only minimally adsorbed to a cation exchange resin, suggesting that the surface membranes of normal leukocytes were charged electronegatively. Adsorbability to anion exchange resin by patients' leukocytes taken from the venous limb of the HD circuit line 15 minutes after starting HD was significantly decreased when using a cellulosic membrane. This suggests that the decrease in electronegative leukocyte surface membrane charge, which may facilitate the attachment of leukocytes to electronegatively charged endothelial cell membranes, is the factor leading to leukopenia. Adsorbability to anion exchange resin by normal leukocytes incubated with plasma taken from HD patients 10 to 60 minutes after starting HD was increased, suggesting an increase in electronegatively charged substances in patients' plasma; these recombine with leukocyte surface membranes thereby increasing the electronegative charges of the leukocyte surface membranes and enabling subsequent release of leukocytes from endothelial cells, consistent with the transient nature of the leukopenia.
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