PubMed Health⌕ Search

Biomedical subjects

Hajime Nakae

Publications and source records attributed to Hajime Nakae.

At least 19 recordsLinked to original sources

Endotoxin adsorption therapy for septic shock using polymyxin B-immobilized fibers (PMX): evaluation by high-sensitivity endotoxin assay and measurement of the cytokine production capacity.

Because of its low sensitivity, the conventional measurement method for endotoxin (ET) is not the most appropriate for monitoring the effect of ET adsorption therapy. Thus, the efficacy of ET adsorption therapy was investigated using a newly developed high-sensitivity ET assay method. The changes in the cytokine production capacity of whole blood were also examined. We treated 24 peritonitis patients who had developed postoperative septic shock with ET adsorption therapy using a column of polymyxin B-immobilized fibers (PMX) and their serum ET levels were measured using the high-sensitivity ET assay based on the kinetic turbidimetric Limulus assay. In addition, the changes in the tumor necrosis factor-(TNF-alpha) production capacity of whole blood following lipopolysaccharide (LPS) stimulation and clinical outcome in the study patients were also examined. The 28-day mortality rate was 12%. PMX-direct hemoperfusion (PMX-DHP) was associated with elevation of the mean arterial pressure and urine output, reduction in the mean dose requirement of vasopressor agents, and recovery from the shock state in all the patients. The PaO2/FIO2 ratio also showed significant improvement. Using the high-sensitivity ET assay, ET was detected in the blood of 20 out of the 24 patients (80%) before the PMX-DHP, and a significant reduction in the ET level was noted after the PMX-DHP. The TNF-alpha production capacity of whole blood, which was found to be lower in the septic shock patients than in healthy subjects, was significantly increased after PMX-DHP. Elimination of ET by PMX-DHP in septic shock patients was confirmed by the high-sensitivity ET assay. PMX-DHP is thus considered to be a useful adjuvant therapeutic technique in the treatment of septic shock. Also, PMX-DHP might alleviate the immunosuppression associated with severe sepsis.

Adsorption↗

Combining continuous endotoxin apheresis and continuous hemodiafiltration in the treatment of patients with septic multiple organ dysfunction syndrome.

When septic multiple organ dysfunction syndrome (MODS) occurs as a result of endotoxemia, diverse chemical mediators are excessively produced, and the patient becomes seriously ill. Under such circumstances, it is difficult to improve the patient's condition by endotoxin apheresis alone and hemodiafiltration should be carried out to remove excessive chemical mediators. Series-parallel treatment combining continuous endotoxin apheresis and hemodiafiltration is recommended for patients with septic MODS.

Blood Component Removal↗

The dose of nafamostat mesilate during plasma exchange with continuous hemodiafiltration in the series-parallel circuit.

We studied nafamostat mesilate (NM) and interleukin (IL)-18 levels to determine whether the dose of NM is reduced during plasma exchange (PE) with continuous hemodiafiltration (CHDF) when the series-parallel circuit is used. The subjects of the current study included four patients with acute hepatic failure who underwent PE with CHDF. The four patients underwent a total 15 PE + CHDF procedures, and for each procedure, they were randomized to receive either a half-dose of NM or no NM in the CHDF circuit. Eight procedures were carried out with NM administration, and seven were carried out without NM administration. The dose of NM in the NM group was significantly higher than that in the non-NM group (P = 0.040). No significant differences were observed between the two groups in the inlet NM concentration, the outlet NM concentration, or the rate of IL-18 removal. No statistical correlation was observed between the IL-18 level and the NM dose, the inlet NM concentration, or the outlet NM concentration. There was no blood access difficulty such as catheter failure or clotting of the filter. Thus, it might be possible to carry out PE and CHDF with the series-parallel method without administration of NM in the CHDF circuit.

Aged↗

Study of safe usage of high-flow three-way stopcocks in a blood circuit.

To examine the safety of using a high-flow three-way stopcock in a blood circuit during extracorporeal blood purification therapy, we studied the risk of development of hemolysis and clot formation in both ex vivo and in vivo extracorporeal circulation. In the ex vivo study, no significant difference was observed in the decrease in hematocrit (HCT) or increase in the potassium level between the three-way stopcock group and the control group. Nor was there a significant difference in the change in inlet pressure between the two groups. Thus, it was shown that the risk of hemolysis caused by the use of a high-flow three-way stopcock on both the outlet side and inlet side would be small. In the in vivo cases, there was no significant difference in the decrease in HCT or the increase in inlet pressure between the three-way stopcock group and control group, suggesting that it is clinically possible to incorporate a high-flow three-way stopcock into a blood circuit.

Arteriovenous Shunt, Surgical↗

Effectiveness of combining plasma exchange and continuous hemodiafiltration in patients with postoperative liver failure.

Nine patients with postoperative liver failure were treated with plasma exchange (PE) or PE and continuous hemodiafiltration (CHDF), and various biochemical parameters were determined before and after treatment. Although citrate levels increased significantly after treatment compared with pretreatment levels in both the PE group and the PE + CHDF group (P < 0.0001 and P < 0.0001, respectively), the percentage of the increase in citrate levels was significantly higher in the PE group than in the PE + CHDF group (P = 0.0051). Total bilirubin (T-Bil) levels were significantly lower after treatment in both the PE and PE + CHDF groups (P < 0.0001 and P = 0.0001, respectively). There were no significant differences in T-Bil levels between the two groups (P = 0.5181). There were no significant differences in interleukin (IL)-6 levels before and after treatment in both the PE and PE + CHDF groups (P = 0.1281 and P = 0.2273, respectively). IL-18 levels were significantly lower after treatment in both the PE and PE + CHDF groups (P < 0.0001 and P = 0.0002, respectively), but there were no significant differences in the removal rate of IL-18 in both the PE and PE + CHDF groups (P = 0.8749). These results indicate that combining PE and CHDF in a series-parallel circuit is an effective modality for suppressing the elevation of blood citrate levels. This finding may have important implications for the development of an effective treatment for patients with postoperative liver failure.

Aged↗

Correlation between serum nafamostat mesilate and activated coagulation time during continuous hemodiafiltration.

We analyzed the relationship between nafamostat mesilate (NM) level and activated coagulation time (ACT) as measured using an Actalyke MINI system vs. an ACTester system in patients with fulminant hepatitis undergoing continuous hemodiafiltration. The hemofilter was made with a polyacrylonitrile membrane, and NM was used as the anticoagulant. Significant correlation was found between the NM dose and the prehemofilter ACT measured by the Actalyke MINI system (r = 0.561, P = 0.0352, n = 14). However, no significant correlation was found between the NM dose and the prehemofilter ACT measured by the ACTester. Neither was a significant correlation found between the prehemofilter NM level and the prehemofilter ACT measured by either system. No significant correlation was found between the NM dose and the posthemofilter ACT measured by either system. The ACTester uses a test tube containing celite and a small amount of kaolin as a coagulation activator. The results of the present study suggest that the ACTester can adsorb NM and that this feature can affect ACT measurement. Considering this influence and the need to minimize the dose of NM in patients with fulminant hepatitis to avoid hemorrhagic tendencies, it is advisable to use the Actalyke MINI system.

Acute Disease↗

The series-parallel circuit in the treatment of fulminant hepatitis.

We developed a series-parallel treatment method for combined plasma exchange (PE) and continuous hemodiafiltration (CHDF) therapy in fulminant hepatitis. We then compared total serum bilirubin, citrate, and cytokine levels obtained by the new methods to those obtained with treatment by the single and reverse-parallel PE methods. Ten adult patients with fulminant hepatitis consented to participate. Plasma exchange was conducted 25 times by the single method (PE only), 16 times by the reverse-parallel method, and 37 times by the series-parallel method. The percentage of total bilirubin removed was highest with the single method followed in order by that with the series-parallel and reverse-parallel methods; the differences were significant. The percentage increase in citrate level was highest with the single method, followed in order by that with the series-parallel and the reverse-parallel methods; these differences were also significant. There was no significant difference in serum interleukin (IL)-6 levels after PE, by the single or the reverse-parallel methods. However, the IL-6 level decreased significantly following PE by the series-parallel method. The serum IL-18 level decreased significantly following PE by each of the three methods. Thus, removal of excess bilirubin, citrate, and cytokines by the series-parallel method, a simple maneuver with excellent removal rates, was considered effective.

Adult↗

Treatment of multiple organ failure through sepsis by surgery and blood purification.

For the treatment of multiple organ failure (MOF) through sepsis, we have commonly applied various blood purification modalities during the perioperative period. From January 1996 to December 2000, 33 patients with MOF through sepsis were admitted and operated on in the First Department of Surgery, Akita University School of Medicine, and 21 of these 33 patients were treated using various blood purification modalities during the perioperative period: endotoxin-adsorbing therapy using polymyxin B (PMX) in 17 patients, continuous hemofiltration (CHF)/continuous hemodiafiltration (CHDF) in 15 patients, and plasma exchange (PE) and CHDF in 3 patients. Of the outcome of these 33 patients with MOF through sepsis, 17 survived and 16 died (48% mortality). Of the 21 patients with MOF through sepsis treated by surgery and blood purification, 12 survived and 9 died (43% mortality). We evaluated APACHE II and the number of failed organs before operation. Amongst the group with 12 survivors and 9 deaths, Acute Physiology and Chronic Health Evaluation II (APACHE II) was 15 +/- 5, 23 +/- 2 and the number of failed organs was 2.7 +/- 0.7, 3.9 +/- 0.8, respectively. An increased APACHE II score and number of failed organs were significantly associated with mortality. As to the treatment of MOF through sepsis due to acute peritonitis, patients with APACHE II scores ranging from 15 to 20, and those with 2-3 failed organs seem to be the candidates for the application of blood purification during the perioperative period.

APACHE↗

Characteristics of self-immolation attempts in Akita Prefecture, Japan.

Akita Prefecture has had the highest suicide rate in Japan for the past 9 years. To obtain further information on suicide attempts by self-immolation in Akita, we performed a statistical analysis of patients in this prefecture who attempted to burn themselves. Over the past 6 years, 541 patients suffering from burns were transferred to medical emergency units. Of these, 35 (6.5%) attempted self-immolation, most of whom were between 20 and 60 years of age. Women over 50 years of age outnumbered men in the same age group. All 35 patients sustained flame burns. The total burn surface area (TBSA), burn index (BI), rate of inhalation injury, and mortality rate were all significantly higher in the patients who attempted self-immolation than in those with nonsuicidal burns. Most (68.6%) of the self-immolation attempts were made indoors. Because the Japanese are not generally a very religious people, training to help them cultivate a philosophy of life and educating them in moral science to help them form a personal view of life and death may be necessary to prevent suicides.

Adolescent↗

Examination of soluble Fas (sFas) and soluble Fas ligand (sFasL) in patients with burns.

The FasL-Fas system is one of the recognized apoptosis-inducing systems, and has been determined to have important functions in relation to homeostasis and biological defense mechanisms. In this study, we investigated the serum levels of soluble Fas (sFas), soluble FasL (sFasL) and tumor necrosis factor alpha (TNF-alpha) in patients with burns. The sFas levels were found to be significantly higher in the patients who eventually died as compared to those in the patients who survived (3.9+/-1.8ng/ml versus 2.6+/-1.0ng/ml). On the other hand, the sFasL levels were significantly higher in the patients who survived (61.5+/-29.9ng/ml versus 37.2+/-14.4ng/ml) than in those who eventually died. A positive correlation was noted between the TNF-alpha level and the sFas level, and a negative correlation was observed between the TNF-alpha level and the sFasL level. These findings suggest that worsening of the condition of a burns patient may be related to changes in the Fas-FasL system.

Adult↗

Pharmacokinetics of nafamostat mesilate during continuous hemodiafiltration with a polyacrylonitrile membrane.

We studied the pharmacokinetics of nafamostat mesilate (NM) used as an anticoagulant in continuous hemodiafiltration (CHDF) with a polyacrylonitrile (PAN) membrane used as the hemofilter. Six patients undergoing CHDF for multiple organ dysfunction syndrome (MODS) were chosen as subjects. The inlet NM concentration measured 24 h after the start of CHDF was significantly greater than that after 1 h (P = 0.0431). No significant difference was observed between the outlet NM concentration and the ultrafilter concentration at 1 h or 24 h after the start of CHDF. However, concentrations at 24 h differed significantly from concentrations at 1 h at all sites. Significant correlation was observed between the dose of NM and the outlet NM concentration (P = 0.0475). No statistical correlation was observed between the dose of catecholamines and the outlet NM concentration (P = 0.0985). This study is the first to disclose a mild but significant time-dependent serum NM concentration in patients with MODS.

Acrylic Resins↗

Matrix metalloproteinase-1 and cytokines in patients with acute pancreatitis.

INTRODUCTION: Hypercytokinemia is known to occur in severe acute pancreatitis, suggesting that the production, deposition, and degradation of the extracellular matrix (ECM) occur actively as a result of the actions of the complicated cytokine network. AIMS AND METHODOLOGY: To examine the influence of cytokines and growth factors on the ECM in acute pancreatitis from the points of view of the severity of the disease, the complication of multiple organ dysfunction syndrome (MODS), and the prognosis, 25 patients with acute pancreatitis were divided into three groups according to the severity of the condition as assessed by the Ranson score. The serum levels of matrix metalloproteinase (MMP)-1, tissue inhibitor of metalloproteinases (TIMP)-1, the MMP-1.TIMP-1 complex, tumor necrosis factor (TNF)-alpha, and transfer growth factor (TGF)-beta1 were determined by enzyme-linked immunosorbent assay. RESULTS: Comparison of the three groups divided according to the severity of the disease revealed significant differences in the levels of MMP-1 and TNF-alpha among the three groups, with the levels being higher in patients with more severe disease. The TIMP-1/MMP-1 ratio and the TGF-beta1 levels were found to be significantly lower in patients with more severe disease. Comparison between the group with the complication of MODS and the group without the complication showed that the levels of MMP-1, the MMP-1.TIMP-1 complex, and TNF-alpha were significantly higher in the former group than in the latter group. The TIMP-1/MMP-1 ratio and the TGF-beta1 levels were significantly lower in the group with the complication of MODS than in the group without the complication. Comparison between the nonsurvivor group and the survivor group revealed significantly higher levels of MMP-1, TIMP-1, and TNF-alpha in the nonsurvivors than in the survivors. The TIMP-1/MMP-1 ratio and the TGF-beta1 levels were significantly higher in the survivors than in the nonsurvivors. A significant correlation was observed between MMP-1 levels and TNF-alpha levels. On the other hand, a significant negative correlation was noted between MMP-1 levels and TGF-beta1 levels. CONCLUSION: The results of our study suggest that the activity of the ECM catabolic enzyme MMP-1 and cytokines are related to the development of acute pancreatitis.

Acute Disease↗

Characteristics of burn patients transported by ambulance to treatment facilities in Akita Prefecture, Japan.

This study analyzes patient demographics and injury data of 342 patients transported by ambulance to emergency facilities in Akita Prefecture, Japan, between 1996 and 2000. Significant findings include the following. Fire was the most frequent cause of burn injury, and winter was the season with the highest incidence (40.6%) of cases. The suicide rate in Akita Prefecture is high, the percentage of burn patients due to suicide attempts was 7.9%. The mean time from burn injury to hospital arrival was significantly longer for patients who later died (44.6 +/- 35.3 min) than for those survived (33.0 +/- 22.5 min). Severely burned patients were not always transported directly to a core emergency facility and an unacceptable number (5.8%) of patients died at tertiary hospitals. This relatively high death rate is attributable to the limited facilities for treating burns in the tertiary hospitals and the long distance to core facilities, which sometimes precludes transport system for the prefecture will reduce transport time to the regional trauma center and thus enable more patients to undergo specialized treatment at an earlier injury stage. Additionally, tertiary facilities should improve their level of burn care (e.g., creating a burn unit and skin bank).

Adolescent↗

Expression of heme oxygenase-1 in the lung and liver tissues in a rat model of burns.

To investigate the functional significance of heme oxygenase (HO)-1 as having anti-oxidant activity in burns, a rat model of 30% burns was prepared, and the lungs and livers were extirpated for immunohistological examination (indirect immunoenzyme techniques). Plasma TNF-alpha levels were significantly higher in the burn group than in the control group, but there was no significant difference in total bilirubin levels between the groups. HO-1 expression was found histologically in the perivascular cells of the lung and liver. It was also found, though only at low levels, in liver parenchymal cells. These results suggest that HO-1 is expressed in the lung and liver tissues in a rat model of burns.

Animals↗

Cytokine removal by plasma exchange with continuous hemodiafiltration in critically ill patients.

The effectiveness of plasma exchange (PE) with continuous hemodiafiltration (CHDF) in the treatment of critically ill patients was evaluated based on changes in cytokine levels. Twenty-six patients with acute hepatic failure were treated with PE (PE group) or PE and CHDF (PE+CHDF group), and the levels of cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 were determined before and after treatment. Bilirubin levels were significantly lower after treatment in both the PE and PE+CHDF groups. There were no significant differences in TNF-alpha levels before and after treatment in the PE group, but the TNF-alpha level was significantly lower after treatment in the PE+CHDF group. There were no significant differences in the IL-6 levels before and after treatment in both the PE and PE+CHDF groups. There were no significant differences in IL-8 levels before and after treatment in the PE group, but the IL-8 level was significantly lower after treatment in the PE+CHDF group. PE with CHDF therapy was given to 5 patients with acutely aggravated autoimmune diseases, 2 patients with hemorrhagic shock and encephalopathy syndrome, and 3 patients with thrombotic microangiopathy. The results suggested that PE with CHDF therapy are useful in critically ill patients with suspected hypercytokinemia.

Adult↗

[Plasma exchange and continuous hemodiafiltration as an initial treatment for diffuse large B-cell lymphoma-associated hemophagocytic syndrome].

A 68-year-old man was admitted to our hospital because of fever, jaundice and hepatosplenomegaly. A diagnosis of diffuse large cell, B-cell type malignant lymphoma, associated with hemophagocytic syndrome (LAHS), was made. CT scan revealed lymphadenopathy in the abdominal cavity and multiple tumors in the spleen. Performance status and hepatic coma grade were 4 and II, respectively. Laboratory findings showed bicytopenia (Hb 9.9 g/dl, platelet 35 x 10(3)/microliter), severe liver dysfunction (ALP 1,115 U/l, gamma-GTP 437 U/l, T.Bil 15.4 mg/dl, D.Bil 12.8 mg/dl) and elevated levels of beta 2 microglobulin (12.9 mg/dl), ferritin (2,300 ng/ml) and sIL-2 receptor (36,900 U/ml). Plasma exchange (PE) and continuous hemodiafiltration (CHDF) enabled the patient to undergo diagnostic procedures, irradiation (total 34 Gy) and chemotherapy. Biopsy specimens revealed infiltration of lymphoma cells into the liver and bone marrow. We measured the blood concentrations of TNF-alpha, IL-6, and IL-8 before and after PE and CHDF by the ELISA method, and found normalization of hypercytokinemia after the procedure. It was suggested that initial treatment with PE and CHDF was effective for control of HPS, enabling us to perform chemotherapy for the lymphoma.

Aged↗