Yamazaki Z

TREATMENT OF INTRACTABLE ASCITES BY CONTINUOUS REINFUSION OF THE STERILIZED, CELL-FREE AND CONCENTRATED ASCITIC FLUID

The new method for continuous reinfusion of sterilized, cell-free and concentrated ascitic fluid is described, and utilized in 72 patients with intractable ascites in both malignancy as well as liver cirrhosis and is described with satisfactory results. The management by repeated ascites reinfusion of patients with benign massive ascites has been possible. This method is capable of being applied to patients with malignant ascites. Symptomatic relief and prolonged survival time is anticipated. The method described in this study is simple and free of adverse effects.

Extracorporkal Inmunoadsorption with In-ph or Imtr Column

In order to selectively remove pathogenic macromolecular reactants, a biological affinity type adsorbent (a DNA colloidin charcoal column or protein A sepharose CL4B = Prosorba) has been developed and used for the treatment of immune disorders, alloimmunization and cancer. However, because physiologically active materials are required in this procedure, it is difficult to ensure an adequate supply of raw materials (and their handling, sterilization and preservation as an immunoadsorbent. To overcome the above-mentioned problems, we developed physicochemical type immunoadsorbents IM-TR and IM-PH, which consist of polyvinyl alcohol gel where tryptophan, in the former, and phenylalanine, in the latter, is used as a ligand. IM-PH has a better selectivity than IM-TR, however, IM-TR is a more efficient adsorbent of anti-acethylcholine receptor antibody than IM-PH. IM-PH plasma perfusion has been successfully used with patients with rheumatoid arthritis, systemic lupus erythematosus (SLE), and multiple sclerosis (MS).

Use of an AR-1 resin column to reduce bilirubin-level in modified ascitic fluid.

Intractable ascites has been accompanied by significant jaundice in some patients. In such cases, a newly developed synthetic resin, AR-1, has been successfully employed to reduce excess bilirubin from the ascitic fluid. This resin has proved to be excellent compared with XAD-2, XAD-7 and activated charcoal, for removal of bilirubin from the plasma and ascitic fluid in our experiments. A column containing 100 ml of AR-1 is inserted in the drip infusion line between the modified ascitic fluid reservoir in the Autoascit device and the patient. This method has been used in 7 cases of intractable ascites associated with advanced gastric, pancreatic, hepatic, rectal and ovarian cancers. The column has sufficient capacity to adsorb excess bilirubin from the modified ascitic fluid. Other biochemical parameters were eseentially unchanged from pre-column values.

Continuous Flow Membrane Plasmapheresis Utilizing Cellulose Acetate Hollow Fiber in Hepatic Failure

The major problems of treatment using hepatic assist devices such as hemoperfusion through charcoal and hemodialysis or hemofiltration with high-permeability membrane include: (Castino et al. 1976) removal of protein-bound toxins is insufficient, (Chirito et al. 1979) the devices cannot be continuously used for the clinically required period, and (Ito et al. 1975) supplementation of defects of the liver’s synthetic functions is insufficient. Plasma exchange with plasmapheresis, which was introduced into treatment of patients with acute hepatic failure by Lepore and Martel (1967) is advantageous in that it not only removes protein-bound toxins but also provides essential nutrients normally supplied by the liver. Unlike exchange transfusion of whole blood, it does not cause hematological problems and for that reason it appears a rational treatment modality for acute hepatic failure. Due to lack of techniques for effective plasma separation, however, it has not been widely used. Therefore its clinical effectiveness in hepatic failure has not been completely confirmed. In recent years, a technique for obtaining large amounts of platelet-free plasma during extracorporeal circulation has been developed by Ito et al. (1975), Castino et al. (1976) and Yamazaki et al. (1977). Therapeutic plasmapheresis with plasma exchange using these techniques in various diseases, including hepatic failure, is now being reviewed.

Significance of various anticoagulation therapies during use of a left ventricular assist device.

A multicomparative study to establish adequate anticoagulation therapy for left ventricular assist devices was undertaken by administrating various anticoagulants: heparin, a prostacyclin analogue combined with a protease inhibitor; thromboxane A2 synthetase inhibitor; or a protease inhibitor alone. Our investigation suggested that combined administration of prostacyclin analogue and protease inhibitor (FUT-175) is ideal anticoagulation therapy from the point of blood coagulation and fibrinolysis. Currently, however, sole administration of FUT-175 is adequate anticoagulation therapy during clinical use of left ventricular assist devices.

Hepatic assist device, using membrane plasma separator and dialyzer

Our hepatic assist device is composed of a membrane plasma separator, blood and plasma pumps, hemodialyzer and controller. Using this device, the patients plasma is replaced with fresh donor plasma in a 5000 ml amount daily. This procedure of plasma exchange takes place in the intensive care unit, until the patient recovers consciousness or cerebral death is confirmed. In the initial results of this plasma exchange, 5 out of 10 patients with fulminant hepatic failure survived. Even with fatal cases, prolongation of survival time was observed. Our hepatic assist device, performing an easy and safe procedure for plasma exchange, appears to be the most promising method of providing long-term hepatic support for acute liver failure at the present time.

Ideal anticoagulation for use with a left ventricular assist device.

To establish ideal anticoagulation therapy for use with a left ventricular assist device, a study was done administering various anticoagulants: heparin, argatroban, a prostacyclin analogue combined with a protease inhibitor, or a protease inhibitor alone. Cardiac asisting by LVAD without any anticoagulants results in marked activation of blood coagulation or fibrinolysis. Administration of argatroban, as well as heparin, produces a bleeding tendency. Administration of a protease inhibitor (nafamostat mesilate, FUT-175) as a sole anticoagulant induces activation of the blood coagulation system to some extent, but it is within acceptable limits. Combined administration of a prostacyclin analogue (PG) and FUT-175 is most effective in maintaining balanced blood coagulation and fibrinolysis.

Pharmacodynamics of FUT-175 anticoagulant in adsorbent plasma perfusion.

FUT, a new synthetic protease inhibitor, has been used recently in hemodialysis as an anticoagulant in patients with bleeding tendencies. As some new adsorbents require alternatives to heparin because of their strong adsorbing capacity for heparin, plasma perfusion with FUT anticoagulation was pharmacodynamically investigated. Blood was pumped from a dog (QB = 50-70 ml/min) into a plasma separator. The separated plasma (QP = 10-20 ml/min) passed through an adsorbent column and was reinfused into the blood that had passed through the plasma separator. FUT was continuously infused, at a flow rate of 50 mg/hr, into the blood as it left the dog and entered the extracorporeal circuit. Blood and plasma samples were taken as it exited the dog (S1), before and after the adsorbent column (S2, S3), and before reinfusion into the dog (S4). Except for that done with a charcoal-column, adsorbent plasma perfusion went well and the dog tolerated the procedure. FUT levels in S2, S3, and S4 provided anticoagulation. However, as the FUT levels in S1 remained negligible, the dogs coagulation time was within normal limits. In conclusion, FUT was pharmacodynamically proven to be a safe and reasonable anticoagulant for adsorbents that adsorb large amounts of heparin and for patients with bleeding tendencies.

A new improved biodegradable tracheal prosthesis using hydroxy apatite and carbon fiber.

A new biodegradable tracheal prosthesis was developed using hydroxyapatite rings as the artificial tracheal cartilage, a carbon fiber tube as the tracheal tube; it was then implanted into the cervical trachea in dogs. Morphologic examination revealed that the hydroxyapatite ring was anchored firmly to the tracheal cartilage by ingrowth of cartilaginous tissue into the macropores of the hydroxyapatite.

Effect of Oral Adsorbent on Blood Metabolites in Hepatic Failure Dogs

AST-120 is a specially synthesized carbonaceous adsorbent for oral use. It mainly adsorbs low to middle molecules in the alimentary tract. In the present study, AST-120 was administered to hepatic failure dogs, and blood metabolites were analyzed by high performance liquid chromatography (HPLC). Thirty adult mongrel dogs underwent posta-cavae (P-C) shunts with 40% and 70% hepatectomies. They were divided into two groups, the AST group (n= 19) and control group (n=11). The AST group received about 0.5 g/kg of the adsorbent intermittently with diet after the operation. The control group was fed the ordinary diet. Body weight, blood ammonia, plasma bile acids were measured, and blood metabolites were analyzed by the multi-column HPLC system. P-C shunt dogs with 70% hepatotectomies died within three months showing about 40–50% body weight loss. HPLC analysis of their plasma showed some specific peaks for middle molecules, about 3000–5000 daltons. After administration of the adsorbent, these peaks were not detected, so it was considered that these substances had been adsorbed.