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K Hanasawa

Publications and source records attributed to K Hanasawa.

36 records · Page 2Linked to original sources

Comparison of acute physiology and chronic health evaluation III and II for prediction of mortality in multiple organ failure patients treated by plasma exchange.

This study examined the efficacy of a different scoring system for multiple organ failure (MOF) patients treated by plasma exchange (PE). Twenty-five patients with MOF resulting from fulminant hepatitis who had been treated by PE for a total number of 91 PEs in a consecutive period of 22 months were included in our study. Data were collected from each patient to compute acute physiology and chronic health evaluation (APACHE) II and APACHE (AP) III scores. The sensitivity, specificity, and correct prediction of outcomes were measured. The correct prediction of outcomes was 86.5%in AP III and 77.5% in AP II. For the prediction of patient mortality, the AP III system seems to be more reliable than AP II.

APACHE↗

Theoretical background of effect mechanism by extracorporeal immunomodulation.

Therapeutic plasmapheresis has usually been applied to diseases with unknown causes. Clear analysis of the mechanism of the effect that apheresis has on diseases derived from unknown causes has not been completed. The effect of leukocytapheresis on ulcerative colitis (UC) or rheumatoid arthritis (RA) also lacks clear analysis, but removal of 10(10) adhesive cells resulted in the suppression of both acute and chronic inflammatory reactions. The number of cells removed was not unreasonable for efficacy. A quite acceptable explanation is that the cells activated in the inflammatory lesions are more adhesive than nonactivated cells. However, only a few minutes of contact with the surface of the device can activate blood immune cells. All of the apheresis therapies, not only leukocytapheresis, should be evaluated for their efficacies, excluding the effects of contact activation. According to results presently available, the suppressive effect of leukocytapheresis on RA or UC is through to depend upon the removal of activated inflammation related cells that might transfer inflammatory signals. It may be that those cells removed are bound because of cell stimulation caused by microorganisms or foreign bodies.

Arthritis, Rheumatoid↗

Blood purification for critical care medicine: endotoxin adsorption.

Many kinds of blood purifying technologies have been applied to the treatment of critically ill patients since 1979 when plasma exchange with hollow-fiber membranes was developed. These technologies have been applied not only to the removal of toxic substances, but also to the treatment of objective diseases and the removal of the factors relating to the associated inflammation. This article summarizes these methods and their efficacies for critically ill patients, especially those with severe sepsis. Attempts have been made to remove endotoxin, the main cause of sepsis, from the circulation using polymyxin B immobilized fiber, charcoal hemoperfusion, and plasma or whole blood exchange. Attempts have also been made to remove proinflammatory cytokines, eicosanoides, and coagulative factors from the circulation in the human body. Continuous hemofiltration or hemodiafiltration is the representative technology. The efficacy of these methods has been established, but several issues remain unresolved. All methods of the treatment of severe sepsis are discussed with reference to treatment indications, efficacy, and outcome parameters. In particular, the clinical results of endotoxin removal with polymyxin B immobilized fiber are summarized in this article.

Adsorption↗

Treatment of sepsis by extracorporeal elimination of endotoxin using polymyxin B-immobilized fiber.

Despite the use of potent antibiotics and intensive supportive care, mortality remains high among septic shock patients, especially those with endotoxemia. To remove endotoxin directly from the blood, a material consisting of polymyxin B that is immobilized on fibers (PMX-F) and that can selectively detoxify endotoxin was developed. In a preliminary clinical study, 16 patients with septic multiple organ failure were treated with direct hemoperfusion using a PMX-F column. This therapy significantly decreased the endotoxin level from 76 pg/mL to 21 pg/mL after 2 hours of direct hemoperfusion. The hyperdynamic state of the cardiac index, which is a characteristic of endotoxic shock, returned to normal levels after treatment. In septic shock patients with a systolic pressure of less than 100 mm Hg, the systolic arterial pressure increased significantly from the pretreatment level. The alleviation of fever caused by this therapy continued until the day after treatment. Of the 16 patients who underwent this therapy, 9 were alive 2 weeks after this therapy and 7 patients were discharged from the hospital alive. Hemoperfusion with PMX may be an effective treatment for sepsis and septic shock.

Biocompatible Materials↗

[Treatment of sepsis by extracorporeal elimination of endotoxin using fiber-immobilized polymyxin B].

To remove endotoxin directly from the blood, an affinity adsorbent (PMX) has been developed. PMX is composed of a ligand of polymyxin B and a carrier of polystyrene fibers. We treated 16 patients, suffering from septic shock or multiple organ failure by PMX-F hemoperfusion. The pretreatment level of endotoxin decreased significantly from 80pg/ml to 21pg/ml on average 2 hours after the hemoperfusion. The hyperdynamic status in the cardiac index and the decreased systemic vascular resistance, which are characteristic to endotoxin shock, were normalized after the treatment. In septic shock patients with systolic pressure under 10mmHg, the systolic pressure increased significantly from pretreatment level. Nine of the sixteen patients remained alive for two weeks after the therapy, and seven out of the nine patients discharged alive. Hemoperfusion with PMX is likely to become an effective treatment for sepsis and septic shock.

Endotoxins↗

[Prevention of postoperative recurrence after hepatic resection for metastatic colorectal cancer by adjuvant locoregional chemotherapy].

Postoperative adjuvant locoregional chemotherapy was performed on patients who underwent hepatic resection for metastatic colorectal cancer. To prevent recurrence in the residual liver after hepatic resection. 7 patients received intra-hepato-arterial infusion of MMC, 5-fluorouracil (5-FU), doxorubicin + Lipiodol emulsion. Sixteen cases did not receive such treatment. The 1-, 2- and 3-year cumulative disease free rates were 100, 80 and 40% in the patients with this adjuvant chemotherapy, against 61.4, 54.6 and 28.1% in those without this locoregional therapy, respectively. The 1-, 2- and 3-year cumulative survival rates were 100, 100 and 60% in the TAI-E group, and 73.7, 63.3 and 63.3% in the patients without TAI-E, respectively. Postoperative adjuvant locoregional chemotherapy is considered effective to prevent the recurrence of metastatic colorectal cancer in the residual liver after hepatectomy.

Aged↗

[Evaluation of the combination of chemotherapy with etoposide, adriamycin and cisplatin (EAP) in advanced or recurrent gastric cancer].

EAP therapy was performed on 30 cases of advanced or recurrent gastric cancer between September 1987 and July 1991. The clinical responses of 15 trial patients were evaluated. The overall response rate was 40.0% (CR, one case; PR 5 cases). The results were thus not as favorable as that reported by Preusser et al. On the contrary, with such a poor response rate, this treatment did not lead to a prolonged life span (mean survival time; 5.6 months, median survival time; 4 months). Side effects, such as myelosuppression, appetite loss, nausea, vomiting, liver dysfunction, renal dysfunction, and alopecia, were also observed. Myelosuppression was a dose-limiting factor. The rhG-CSF proved in 4 cases to be a clinically useful tool against the neutropenia induced by this treatment. It may be concluded that EAP should be given to the following selected patients: (1) those whose condition is not so far advanced: (2) those who have not received many other forms of treatment; and (3) those in excellent general physical condition.

Adult↗

Endotoxin filtration and immune stimulation improve survival from gram-negative sepsis.

Polymyxin B, when bound to a polystyrene fiber (PMX-F), has been used experimentally as an extracorporeal blood filter to reduce serum lipopolysaccharide levels, which are believed to be responsible for physiologic alterations in the septic state. To validate our theory that a combination of PMX-F, systemic antibiotics, and immune stimulation would improve survival, 78 rats were given intravenous doses of Escherichia coli (range, 4.6 to 6.2 X 10(8) colony-forming units/ml). They were then randomized into groups receiving either systemic gentamicin (n = 10); pretreatment with muramyl dipeptide (n = 11); or extracorporeal hemoperfusion through either a sham column (n = 8), PMX-F-packed column with systemic gentamicin (n = 8); or PMX-F-packed column with systemic gentamicin and muramyl dipeptide pretreatment (n = 8). Thirty-three control rats received no treatment. Sham hemoperfusion (13%) and control (21%) rats had the lowest survival rate, although increased improvement was noted in rats treated with gentamicin (30%) or the combination of PMX-F filtration and gentamicin (50%). The most significant improvements occurred in rats pretreated with muramyl dipeptide (53%) and in rats treated with a combination of PMX-F, gentamicin, and muramyl dipeptide (88%). These data show that lipopolysaccharide filtration and nonspecific immune stimulation are additive to antibiotic therapy and are useful as adjunctive measures in the multimodal treatment of experimental gram-negative bacterial infection.

Acetylmuramyl-Alanyl-Isoglutamine↗

Therapeutic plasmapheresis for post-operative hepatic failure.

It goes without saying that post-surgical hepatic failure must be treated. But today, the prognosis is very poor. The reasons for this are that HF is usually accompanied by hemostatic disorders and PHF, and the patients have fresh wounds and are under surgical stress. Moreover, there is no treatment, except PE, and this requires an anticoagulant. Nafamostat Mesilate (FUT-175) was invented as a serine protease inhibitor. It is short acting, and its degradation does not require the liver. FUT-175 was applied as an anticoagulant to 15 PHF patients with bleeding. There were no side effects and no aggravation of bleeding. Based on these results, FUT-175 is thought to be an ideal anticoagulant.

Anticoagulants↗

Experimental study on the adsorption of excess heparin with anion exchange resin fiber.

Anion exchange resin fiber (Ionex) was used as a heparin adsorbent. Ionex has the adsorption capacity of 70 mg/g (weight by desiccation) for heparin, and was used in an attempt to remove the heparin from blood-perfused artificial organs, before the blood was transfused back into the patients. In the ex vivo study, the 5 systemically heparinized dogs (500 U/kg) were treated with a 35-40 g column of Ionex, by direct hemoperfusion (DHP). The concentration of heparin was significantly reduced, within 15 to 60 minutes, using the Ionex. This suggested the possibility of removing excess heparin from the living body. In in vitro, the relationship between the amount of heparin by Ionex and the blood-flow volume were evaluated. Whole blood taken from dogs was added to 5 U/ml of heparin. This was then introduced into a small column containing 0.9 g Ionex, at blood-flow rates of 0.8, 1.6, and 3.2 ml/min. A good adsorption capacity was shown at the blood-flow rate of 0.8 ml/min. One possible explanation for this is that the heparin dispersed in the blood cells gradually was passed on into the plasma and, so, did not have time to be adsorbed at the faster flow rates.

Adsorption↗

New approach to endotoxic and septic shock by means of polymyxin B immobilized fiber.

Endotoxin shock therapy has not been successfully dealt with pharmacologically. Circulation of endotoxins in the blood is an important factor in the pathogenesis and clinical symptoms of endotoxic shock. We have recently developed polymyxin immobilized fiber (PMX-F) as a biomaterial for selectively detoxifying endotoxins. In ex vivo experiments, direct hemoperfusion (DHP) by PMX-F was performed on dogs injected with purified endotoxin. Only one of eight survived in the control group, but ten of 12 survived in the group receiving DHP with PMX-F. Mortality in the treated group decreased remarkably. Thus, the results indicate the efficacy of PMX-F in neutralizing endotoxins. By the same method as already mentioned, DHP with PMX-F was carried out on live dogs with Escherichia coli induced sepsis. All of the dogs in the control group died within 18 hours after bacterial infusion. All of the dogs in the treated group, however, survived for more than three days. Two of the five dogs are still alive. One of the remaining two survived for seven days and the other, 14. We found that PMX-F treatment prolonged or increased the survival rate in the endotoxic and septic dogs.

Animals↗

[Usefulness of endotoxin removal from the septic blood with direct hemoperfusion using PMX-F].

UNLABELLED: Sepsis and septic shock have been drugs difficult to treat despite many our therapeutic methods. There are many drugs for sepsis, but few can remove or detoxify such sabstances as endotoxin. The polystyrene fiber immobilized polymyxin B (PMX-F) have been invented and it was already confirmed the stability of its bonding. In this paper, mass-productive PMX-F for the clinical application were estimated. IN VITRO STUDIES: PMX-F adsorbed endotoxin (10ng/ml) from the calf serum, and recombinant tumor necrosis factor (80U/ml) from the serine solution. PMX-F maintained an antimicrobial activities against E.coli sufficiently. Those activities of PMX-F showed significant difference between PMX-F and carrier fiber. But PMX-F could not adsorb histamine and thromboxane B2. In vivo studies: The treatment of endotoxic mongrel dogs showed early recovery in arterial blood pressure, and ameliorated survival rate significantly. In human study, 77-year old male patients who had obstructive jaundice due to recurrent stomach cancer and biliary tract infection by Klebsiella showed sepsis and DIC. During DHP with PMX-F, the change of blood pressure was remarkable better, and platelet counts decreased, but next morning this count recovered completely and he had no hemorrhagic tendency. We believe clinical application of PMX-F is safe and useful.

Adsorption↗

Novel mechanical assistance in the treatment of endotoxic and septicemic shock.

Systemic sepsis is a frequent and fatal complication of postoperative patients. More recently, therapeutic trials of plasma or blood exchange are performed in septic patients for the purpose of reducing both endotoxins and albumin-bound toxins. As an alternate approach such as this for the removal of endotoxin directly from the blood, the authors recently developed polymyxin B immobilized fiber (PMX-F) as a biomaterial for selectively detoxifying endotoxin. That this newly invented PMX-F neutralizes a sufficient amount of endotoxin in vitro was reported previously. In ex vivo experiments, direct hemoperfusion by PMX-F was performed on purified endotoxin injected canine and on live Escherichia coli induced septic dogs. Only 5% (1/20) survived in the control group, but 75% (30/40) survived in the treated group. Septic dogs died within 18 hours after bacteria infusion in the control group. But all in the treated group survived 3 days. Forty percent of them survived permanently. These observations indicate that PMX-F treatment, namely selective removal of endotoxin in the endotoxic and septicaemic dogs prolongs or increases the chances of survival. Blood compatibility of PMX-F was also evaluated both in vitro and in vivo. With platelets it was shown to be fairly good and with red blood cells, white blood cells, and proteins, extremely good. A preclinical study on the efficacy and safety of PMX-F throughout widespread experiments has just ended.

Animals↗