PubMed Health⌕ Search

Biomedical subjects

T Akizawa

Publications and source records attributed to T Akizawa.

At least 109 records · Page 6Linked to original sources

Clinical application of Fragmin (FR-860) in hemodialysis: multicenter cooperative study in Japan.

A multicenter cooperative study was designed to evaluate the efficacy and safety of Fragmin (FR-860) as an anticoagulant in hemodialysis. Sixty-one stable maintenance hemodialysis patients were enrolled from 14 institutions in Japan. The study period was fixed at 2 weeks. Dosage requirements were 15.0 to 20.0 anti-Xa U/kg as bolus and 7.5 to 10.0 anti-Xa U/kg/hr as continuous infusion. The total dosage of Fragmin was 2505 +/- 127 anti-Xa U compared with 6124 +/- 190 U of conventional heparin. No differences were observed in residual blood in extracorporeal circuits between the groups. The hemostasis times at puncture sites after completion of dialysis were significantly shortened in the Fragmin group (7.9 +/- 0.7 minutes) when compared with the conventional heparin group (11.4 +/- 1.1 minutes; p less than 0.01). Plasma anti-Xa levels were 0.24 +/- 0.03 and 0.36 +/- 0.04 U/ml 1 hour after the initiation and at the completion of dialysis, respectively. ACTs, measured by the Hemochron method, were not prolonged during dialysis. APTTs varied from 34.3 +/- 1.2 before dialysis to 41.0 +/- 1.9 (p less than 0.01) 1 hour after the start of dialysis and 39.9 +/- 1.6 seconds (p less than 0.01) at the end of dialysis. Plasma AT III activity increased from 96.8 +/- 2.5% before dialysis to 113.0 +/- 3.2% (p less than 0.01) at the end of dialysis. No significant changes were observed in both ADP- and collagen-induced platelet aggregation during dialysis. Dialysis efficiency was the same for both groups. Slight itching developed in one of 61 cases. No abnormal laboratory data were observed during the study. The efficacy, safety, and utility rates were 98.4, 98.5, and 98.4%, respectively. Fragmin proved to have a higher utility rate and was a good and convenient alternative to conventional heparin as an anticoagulant in hemodialysis treatment.

Antithrombin III↗

[Beneficial characteristics of protease inhibitor as an anticoagulant for extracorporeal circulation].

Clinical characteristics of protease inhibitor, nafamostat mesilate (FUT-175:FUT), as an anticoagulant for extracorporeal circulation (ECC) were evaluated in hemodialysis and membrane plasmapheresis. FUT inhibited broad enzymatic systems including coagulation, platelet, complement, fibrinolysis and kinin cascades, which were commonly activated in the course of ECC. FUT showed regional anticoagulability, in which anticoagulating effects were firmly limited in extracorporeal circuit, and hemostatic time after ECC was significantly shortened by the use of FUT. FUT had no effects on lipid and bone metabolisms and FUT could not be adsorbed to anion exchange resin. These results indicate that FUT possesses superior characteristics as an anticoagulant for ECC to heparin, and FUT is very useful especially for ECC of patients with high bleeding risk.

Anticoagulants↗

[The effects of r-HuEPO on platelet function and coagulation factors in hemodialysis patients].

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)

Adult↗

Elimination of beta 2-microglobulin by a new polyacrylonitrile membrane dialyser: mechanism and physiokinetics.

The performance and mechanism of beta 2-microglobulin (beta 2 M) removal by a new polyacrylonitrile membrane dialyser (CX2), and the physiokinetics of beta 2 M during treatment were studied. In vitro experiments showed that mean pore size of the CX2 membrane was 120 A, and the molecular cut-off point was less than 66,000 daltons. The diffusive capacity of the PAN 12CX2 dialyser (1.2 m2) for beta 2 M was calculated to be 27.3 ml/min at a blood flow of 200 ml/min, and it was considered that, compared to the elimination by local filtration induced by back-filtration and adsorption, diffusion was the major eliminating mechanism for beta 2 M. Although the elimination of beta 2 M increased linearly by augumentation of the ultrafiltration volume, diffusion was a major contributing factor for beta 2 M removal even in haemodiafiltration. Serum beta 2 M decreased to 51% and 44% of initial values after correction of haemoconcentration by a clinical haemodialysis or haemodiafiltration even under relatively low blood and filtrate flow conditions, and sieving coefficient and clearance of CX2 for beta 2 M compared well with in vitro results. The one-pool model simulation demonstrated that from 50 to 60 mg of beta 2 M was transferred from the intra- to the extracellular space during treatment. These results indicate that CX2 effectively eliminates beta 2 M mainly by diffusion, and that beta 2 M transfer to the plasma space during haemodialysis and haemodiafiltration may be accelerated.

Amyloidosis↗

HTLV-1 rex and HIV-1 rev act through similar mechanisms to relieve suppression of unspliced RNA expression.

Human retroviruses, human T cell leukemia viruses (HTLV) and human immunodeficiency viruses (HIV), express two classes of mRNAs; fully spliced mRNA in the early phase and intron-containing mRNA in a later phase. The expressions of HTLV-1 rex and HIV rev by early mRNAs are essential for the later phase of expression of intron-containing gag and env mRNAs. Each two cis-acting sequences seem to be involved in these regulations: HTLV-1 rex depends on a splice donor (SD) and a responsible element (RXE) at the 3' end, whereas HIV rev depends on a specific repressive sequence (CRS) and a responsible element (RRE) in the intron, but does not require an SD. For analyses of these cis-acting sequences, we inserted an HIV element RRE into an HTLV-1 construct and tested the responses to HTLV-1 rex and HIV rev regulations. The results indicated that both rex and rev could regulate RNA expression of these chimeric constructs responding to an HIV RRE. A repressive element (CRS) was dispensable, and the intronic or exonic location of RRE was not important. These observations suggest that rex and rev could be functionally equivalent to induce cytoplasmic expression of unspliced RNA which expression is suppressed either by an SD or CRS depending on the construction.

Cell Line↗

Prevalence of HTLV-1 antibodies in hemodialysis patients in Japan.

The southwestern region of Japan is known as a very high endemic area of human T-cell lymphotropic virus type 1 (HTLV-1), the etiologic agent for adult T-cell leukemia (ATL) and probable causative agent for tropical spastic paraparesis and its Japanese version, HTLV-1-associated myelopathy (HAM). Hemodialysis (HD) patients seem to be at high risk for HTLV-1 infection even in other regions of Japan because they sometimes receive multiple blood transfusions. We examined antibody against ATL-associated antigen (ATLA-Ab) in 1,132 HD patients, including 1,066 patients in nonendemic areas (Chubu and Tokyo) and 66 in a highly endemic area (Okinawa). The HD patients in Okinawa showed the highest prevalence, 21.2% (14/66), while those in the Chubu area showed the lowest, 1.1% (10/846), and those in the Tokyo area an intermediate value, 2.7% (6/220). The prevalence of HD patients in each area was significantly higher than that of local blood donors, reflecting an increased prevalence roughly corresponding to the respective endemic rate. The average prevalence of ATLA-Ab among the HD patients was 2.7% (30/1,132), which was similar to that of HBs antigen (3.2%). In the nonendemic areas, 15 of 16 patients with ATLA-Ab had a history of blood transfusions, showing a significant correlation to the presence of ATLA-Ab (P less than 0.01), although four had family histories related to the endemic area. The relative risk of the presence of ATLA-Ab for HD patients with a history of blood transfusions was calculated as 10.3. In the endemic area of Okinawa, the relationship to blood transfusion was not so close, probably masked by the high background prevalence.

Adult↗

Evaluation of beta 2-microglobulin removal with high-performance hemodiafiltration.

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.

Adult↗

Clinical effect of recombinant human erythropoietin on anemia associated with chronic renal failure. A multi-institutional study in Japan.

Clinical effect and safety of recombinant human erythropoietin (r-HuEPO) were evaluated in 66 hemodialysis patients with intractable anemia. Initially, 50U/kg dry weight (DW) of r-HuEPO was administered intravenously at the end of every hemodialysis procedure for 4 weeks, then the dosage was increased to 100 and 200U/kg DW for poor responders. The patients' hematocrits rose from 19.8 +/- 2.3% (pretreatment) to 30.2 +/- 4.9% after 12 weeks. From 206 U of blood transfusion requirement in the 3-month period before the study, only 34 U were needed after treatment. Serum iron and ferritin levels fell significantly during the study, and iron storage was considered to be one of the decisive factors in the response to r-HuEPO. Blood pressure rose in the course of r-HuEPO administration, but uncontrollable hypertension was rarely observed. There was no significant adverse effect of r-HuEPO except for this mild hypertension. These results indicate that r-HuEPO is an excellent therapeutic aid for the anemia associated with chronic renal failure.

Adult↗

Activities of novel polyhydroxylated cardiotonic steroids purified from nuchal glands of the snake, Rhabdophis tigrinus.

Seven novel polyhydroxylated steroids were isolated from the nucho-dorsal glands of the snake, Rhabdophis tigrinus. Biological activities of these steroids in inhibiting (Na+ + K+)ATPase and in producing positive inotropic action were examined in comparison with those of ouabain and gamabufotalin. Gamabufotalin was approximately 10 times more potent than ouabain in inhibiting (Na+ + K+)ATPase. Two compounds, compounds III and XIII, of the seven, produced nearly equipotent enzyme inhibitory activity to ouabain. The activity of the remaining five was relatively low among the compounds tested. All compounds exhibited more or less positive inotropic action in the papillary muscle preparations. The ranking order of the potency was: gamabufotalin greater than ouabain and compound IV greater than compound III and XIII greater than compound I, II, XII and XIV.

Amphibian Venoms↗