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Biomedical subjects

Toshiaki Iba

Publications and source records attributed to Toshiaki Iba.

At least 19 recordsLinked to original sources
PubMed2006

A multicenter, prospective validation of disseminated intravascular coagulation diagnostic criteria for critically ill patients: comparing current criteria.

OBJECTIVES: To validate scoring algorithm criteria established by the Japanese Association for Acute Medicine (JAAM) for disseminated intravascular coagulation (DIC) and to evaluate its diagnostic property by comparing the two leading scoring systems for DIC, from the Japanese Ministry of Health and Welfare (JMHW) and International Society on Thrombosis and Haemostasis (ISTH). DESIGN: Prospective, multicenter study during a 3-month period. SETTING: General critical care center in a tertiary care hospital. PATIENTS: Two hundred seventy-three patients with platelet counts<150x109/L were enrolled. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The JAAM, JMHW, and ISTH DIC scoring algorithms were prospectively applied within 12 hrs of patients meeting the inclusion criteria (day 0) to days 1-3, by global coagulation tests. The numbers of systemic inflammatory response syndrome (SIRS) criteria and Sequential Organ Failure Assessment (SOFA) scores were determined simultaneously. Mortality associated with any cause was also assessed 28 days after the enrollment. All global coagulation tests and SIRS criteria adopted in the JAAM criteria and their cutoff points were validated with use of SOFA scores and mortality rate. DIC diagnostic rate of the JAAM DIC scoring system was significantly higher than that of the other two criteria (p<.001). The JAAM DIC algorithm was the most sensitive for early diagnosis of DIC (p<.001). PATIENTS who fulfilled the JAAM DIC criteria included almost all those whose DIC was diagnosed by the JMHW and ISTH scoring systems. The JAAM DIC scores showed significant correlation with SOFA scores ([rho]=0.499; p<.001). SOFA score and mortality rate worsened in accordance with an increase in the JAAM DIC score. Fibrinogen criteria had little effect in predicting outcome for the DIC patients, and a total score of 4 points in the JAAM scoring system without fibrinogen was closely related to poor prognosis. According to the results, we revised the JAAM criteria by excluding fibrinogen and confirmed that the DIC diagnostic properties of original criteria remained unchanged in the revised JAAM criteria. CONCLUSIONS: The JAAM scoring system has an acceptable property for the diagnosis of DIC. The scoring system identified most of the patients diagnosed by the JMHW and ISTH criteria. Revised JAAM DIC criteria preserved all properties of the original criteria for DIC diagnosis. The revised scoring system can be useful for selecting DIC patients for early treatment in a critical care setting.

Algorithms↗
PubMed2006

Pretreatment of sivelestat sodium hydrate improves the lung microcirculation and alveolar damage in lipopolysaccharide-induced acute lung inflammation in hamsters.

Damage to the lung microcirculation and alveoli caused by activated leukocytes is known to play an important role in the development of acute lung injury (ALI). The aim of this study is to evaluate the difference in the effect of pretreatment and posttreatment of a synthetic neutrophil elastase inhibitor sivelestat on ALI. Hamsters were instilled with 10.0 mg/kg of lipopolysaccharide (LPS) intratracheally for 1 h to simulate ALI. Two milligrams per kilogram of sivelestat was injected intraperitoneally either previously or after LPS infusion. One and 24 hours after the infusion of LPS, pulmonary microcirculation was observed under the intravital microscopy. In another series, the blood cell counts were evaluated. The adhesive leukocyte count on the endothelium was significantly lower in pretreatment group compared with control group (P < 0.01), whereas the difference was not significant in the posttreatment group. Similarly, the number of obstructed capillary was significantly lower in the pretreatment group (P < 0.01). The width of interstitium was significantly lower in the pretreatment and posttreatment group (P < 0.01 and 0.05, respectively). A comparison of white blood cell counts showed a better maintenance in pretreatment group (P < 0.05). Pretreatment of sivelestat demonstrated a protective effect on both intravascular and extravascular damage in the lung, whereas posttreatment only suppressed the latter damage.

Acute Disease↗
PubMed2006

Comparison of the protective effects of type III phosphodiesterase (PDE3) inhibitor (cilostazol) and acetylsalicylic acid on intestinal microcirculation after ischemia reperfusion injury in mice.

Antiplatelet therapy has been proposed as the treatment of choice for ischemia/reperfusion injury. The aim of this study is to elucidate the difference in effect between cilostazol (CZ) and acetylsalicylic acid (ASA) on microcirculatory disturbance in ischemia/reperfusion injury. Either 10 mg/kg of CZ (n = 14) or 100 mg/kg of ASA (n = 14) was administered orally to mice. Thereafter, 20 min of intestinal ischemia, followed by 60-min reperfusion, was applied; then, the status of submucosal microcirculation was observed under intravital microscopy. The blood cell counts and organ damage markers were examined in the portal blood. Next, 5 mm of the ileum was excised and was then histologically examined. Platelet-leukocyte aggregates were often observed in the postcapillary venules, and this formation was significantly reduced by both CZ and ASA. The number of adherent leukocytes was significantly lesser in the CZ-treated mice than in the ASA-treated mice (P < 0.01). The leukocyte number, lactate dehydrogenase, and lactate levels were best maintained in the CZ-treated mice (P < 0.05). The villus height was best preserved in the CZ-treated mice. Cilostazol inhibited not only the platelet aggregation but also the leukocyte adhesion to the endothelium, thereby inducing organ protection.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2006

Evaluation of haemostatic molecular markers for diagnosis of disseminated intravascular coagulation in patients with infections.

Early treatment of disseminated intravascular coagulation (DIC) is recommended but global coagulation tests used in authorized DIC criteria are not sensitive for diagnosis of early-phase DIC. We examined the plasma levels of thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC) and D-dimer in patients with suspected DIC to determine the cutoff values for diagnosis of DIC. Plasma levels of D-dimer, TAT and PPIC were significantly elevated in patients with DIC and correlated with DIC score. The cutoff values were determined using the receiver operative curve analysis. The cutoff value represented the point at which the sensitivity curve crossed the specificity curve. The cutoff values of D-dimer, TAT and PPIC for DIC were 12.0 mug/ml, 11.0 ng/ml and 1.8 mug/ml, respectively. These values were moderately to highly sensitive for the diagnosis of DIC but not for poor outcome. The combination of D-dimer, TAT and PPIC showed high sensitivity and low specificity when one or more tests were positive, but showed low sensitivity and high specificity when all three tests were positive. We conclude that hemostatic molecular markers might be useful for the diagnosis of DIC and should be confirmed by several trials.

Aged↗
PubMed2005

Antithrombin ameliorates endotoxin-induced organ dysfunction more efficiently when combined with danaparoid sodium than with unfractionated heparin.

OBJECTIVE: This study investigated the potential benefits of combination therapy using antithrombin (AT) with danaparoid sodium (DA) compared with the use of AT with unfractionated heparin (UFH) in the treatment of sepsis. METHODS: Rats infused with lipopolysaccharide were treated with either DA alone, AT alone, AT plus DA, AT plus UFH, or human serum albumin as controls. AT (125 U/kg) was injected into the AT group immediately after lipopolysaccharide infusion. The AT/DA and AT/UFH groups received the same dose of AT in conjunction with either DA (400 U/kg) or UFH (400 U/kg). The status of the mesenteric microcirculation was examined by intra-vital microscopy and the laboratory indices of coagulation, inflammation, and organ dysfunction were measured. RESULTS: The coagulation markers were improved following the administration of DA or UFH. The decreases in the WBC counts were significantly suppressed in the AT/DA group. The elevation of IL-6 decreased in the AT, DA, and AT/DA groups (all p<0.01) but not in the AT/UFH group. The prostaglandin I2 levels were significantly elevated only in the AT/DA group (p<0.05). The WBC adhesion was significantly suppressed in the DA, AT/UFH, and AT/DA groups (p<0.05), and the RBC velocity was best maintained in the AT/DA group with no associated increase in capillary hemorrhage. The elevation of ALT and BUN significantly improved only in the AT/DA group. ONCLUSION: Organ dysfunction can thus be alleviated by even moderate doses of AT replacement when co-administered with DA.

6-Ketoprostaglandin F1 alpha↗
PubMed2005

Laparoscopy-assisted low anterior resection with a prolapsing technique for low rectal cancer.

Laparoscopy-assisted low anterior resection (LAR) for low rectal cancer is a difficult procedure, presenting problems with rectal washout, selecting the appropriate distal transection line, and achieving safe anastomosis. To resolve these problems, we used a prolapsing technique to perform laparoscopy-assisted LAR. Total mesorectal excision (TME) is performed laparoscopically. The proximal colon is transected laparoscopically with the aid of an endoscopic stapler, and the distal rectum, including the lesion, are everted and pulled transanally to outside the body. Only washout of and wiping off the distal rectum and intestinal resection are performed extracorporeally. The distal rectum is pushed back through the anus into the pelvis, and intracorporeal anastomosis is completed laparoscopically with a double-stapling technique. Our limited experience suggests that the prolapsing technique helps to prevent problems with laparoscopy-assisted LAR in selected patients with low rectal cancer.

Colectomy↗
PubMed2005

Activated protein C improves the visceral microcirculation by attenuating the leukocyte-endothelial interaction in a rat lipopolysaccharide model.

OBJECTIVE: Abnormalities in the vascular endothelial function play an important role in the development of septic organ dysfunction. The aim of the study was to examine the effect of recombinant human activated protein C on leukocyte-endothelial interaction in endotoxemia. DESIGN: Experimental animal model of sepsis. SETTING: University research laboratory. SUBJECTS: Normal Wistar rats. Each animal was infused with 4.5 mg/kg lipopolysaccharide to simulate severe sepsis. INTERVENTIONS: Rats were injected with endotoxin simultaneously with either a low or a high dose of recombinant human activated protein C (n = 7). One, 2, and 3 hrs after injection, mesenteric microcirculation was observed under intravital microscopy. In another series, tumor necrosis factor, interleukin-6, alanine transaminase, and blood urea nitrogen levels were evaluated (n = 5). MEASUREMENTS AND MAIN RESULTS: The adhesive leukocyte count on the endothelium was significantly suppressed in both high-dose and low-dose groups (p < .01 and .05, respectively). The bleeding events decreased in the low-dose treatment group compared with both the control (p < .05) and high-dose group (p < .05). Microcirculatory flow as expressed by red blood cell velocity was maintained better in the low-dose group. Comparison of cytokine levels showed a significant decrease in the treatment groups. Organ damage markers were also suppressed in the treatment groups (p < .05) CONCLUSIONS: Recombinant human activated protein C demonstrated a protective effect on microcirculation through the inhibition of leukocyte-endothelial interaction and suppression of inflammatory cytokine production.

Alanine Transaminase↗
PubMed2005

Association between the severity of sepsis and the changes in hemostatic molecular markers and vascular endothelial damage markers.

It is well known that disorders of coagulation and fibrinolysis play a major role in the development of organ dysfunction during sepsis. Furthermore, the importance of the early initiation of anticoagulation therapy for severe cases has been emphasized based on the success of recent clinical trials. The purpose of this study is to search for useful markers for predicting organ dysfunction. Plasma samples were prospectively collected from 78 patients within 48 h after the onset of sepsis. Hemostatic markers and endothelial damage markers were compared between the patients with and without organ dysfunction. The WBC and platelet counts were not different between the groups. In contrast, fibrin/fibrinogen degradation products, D-dimer, thrombin-antithrombin complex, plasmin alpha2-antiplasmin complex, soluble fibrin, and total plasminogen activator inhibitor-1 were significantly higher, and the antithrombin activity and protein C levels were lower in the patients with organ dysfunction. Thus, the changes in the hemostatic molecular markers were associated with organ dysfunction from an early stage of sepsis, and antithrombin and protein C activities were found to be the most reliable markers.

Adult↗
PubMed2005

Evaluation of new Japanese diagnostic criteria for disseminated intravascular coagulation in critically ill patients.

New Japanese diagnostic criteria were prepared for disseminated intravascular coagulation (DIC) in critically ill patients and their usefulness was compared with the criteria of the International Society of Thrombosis and Haemostasis (ISTH) and those of the Japan Ministry of Health and Welfare (JMHW). In a retrospective study of patients with platelet counts of less than 150 x10(3)/mL, 52 cases (33.3%), 66 cases (42.3%), and 101 cases (64.7%) were diagnosed as DIC by the ISTH, JMHW, and new Japanese DIC criteria, respectively. The DIC state as diagnosed by the new Japanese DIC criteria included both DIC states as diagnosed by ISTH or JMHW criteria. Some DIC states diagnosed by the JMHW criteria included those diagnosed by ISHT criteria but this was not universal. The mortality of DIC as diagnosed by the ISTH or JMHW criteria was markedly high, compared to that for DIC diagnosed by the new Japanese criteria. The mortality of patients without DIC by ISTH was also high when they were diagnosed as DIC by the new Japanese criteria. The frequency of DIC by each set of diagnostic criteria was significantly higher in patients with infection than in those without infection. The mortality of DIC by each set of diagnostic criteria was significantly higher in patients with infection than in those without infection, and the mortality of overt-DIC by ISTH diagnostic criteria was also high in patients without infection.

Critical Illness↗
PubMed2004

The efficacy of long-term oral chemotherapy with 5'-deoxy-5-fluorouridine and cyclophosphamide for recurrent breast cancer.

BACKGROUND: 5'-Deoxy-5-fluorouridine (5'-DFUR) is a prodrug of 5-fluorouracil (5-FU), which is known to be converted by thymidine phosphorylase (dThdPase). A recent preclinical study revealed that cyclophosphamide (CPA) upregulated dThdPase activity, specifically in tumor cells. The purpose of the present study was to examine the efficacy of long-term administration of 5'-DFUR/CPA for patients with recurrent breast cancer. METHODS: Fifteen breast cancer patients with recurrent tumors entered this study. Ten patients had bone metastasis, five had lung metastasis, and two had liver metastasis. Three patients had multiorgan metastases. All patients had had previous exposure to standard chemotherapy such as CAF (CPA, doxorubicin, and 5-FU) and CMF (CPA, methotrexate, and 5-FU). The patients were orally administered with daily doses of 5'-DFUR at 800-1200 mg and CPA at 200 mg for 2 weeks as induction therapy, followed by 2 weeks' rest (one to two cycles). Daily doses of 800 mg of 5'-DFUR and 100 mg of CPA (as maintenance therapy) were continuously administered thereafter. Ten of the 15 patients received the maintenance therapy alone. The treatment was continued for at least 24 months (average, 35.2 months). RESULTS: The main findings included a significant decrease in pain in nine patients with bone metastasis, and this effect continued for more than 2 years. As the pain decreased, the patients' quality of life (QOL) was improved. Liver metastasis was diminished in two out of two patients. Hematological toxicity of more than grade 3 was recognized in three patients, but only during the induction therapy. CONCLUSION: Oral administration of 5'-DFUR/CPA is well tolerated and useful for patients with recurrent breast cancer.

Administration, Oral↗
PubMed2004

Laparoscopic surgery for left paraduodenal hernia.

Paraduodenal hernia is a rare condition but the most common internal hernia. We describe the case of a 51-year-old man who was admitted with a complaint of 2 months' duration of recurrent left lower abdominal pain. Left paraduodenal hernia complicated by bowel malrotation was diagnosed, and the patient underwent laparoscopic surgery since no bowel necrosis was observed. The bowel incarcerated in the hernial sac was reduced, and an Endostitch was used to close the hernial orifice with continuous sutures. The postoperative course was good, and the patient was discharged 7 days after surgery. For paraduodenal hernia without bowel necrosis, particularly a left hernia, reduction of the incarcerated bowel and closure of the hernial orifice are relatively easy in terms of technique, and laparoscopic surgery may be the surgical method of choice because of its minimal invasiveness and aesthetic advantage.

Duodenal Diseases↗
PubMed2004

[Activated protein C (the impact of PROWESS trial)].

The inflammatory response in severe sepsis is integrally linked to procoagulant activity and endothelial activation. The abnormalities in the microcirculation results in the development of septic organ dysfunction. The natural anticoagulant activated protein C is expected not only to improve the unbalanced coagulation/fibrinolysis system, but also to modulate the endothelial function, and to express the anti-inflammatory properties. To certify these effects, a large scale, multiple center, randomized, placebo controlled phase 3 trial (PROWESS trial) has been conducted. The results showed the statistically significant improved survival in patients with sepsis induced organ dysfunction (absolute risk reduction in 6.1%). As a result, activated protein C is recommended in patients at high risk of death such as Acute Physiology and Chronic Health Evaluation II > or = 25. However, since bleeding risk is reported as an adverse effect, activated protein C is contraindicated in patients with bleeding tendency.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Antithrombin modulates the leukocyte-endothelial cell interaction in the staphylococcal enterotoxin B-challenged mouse.

BACKGROUND: The beneficial effects of antithrombin on endotoxemia are well known. The purpose of this study was to examine the effects of antithrombin in a supertoxin-induced sepsis. METHODS: Mice were injected with staphylococcal enterotoxin B simultaneously with antithrombin. At 1 hour after injection, the mesenteric microcirculation was observed under intravital microscopy. In addition, humoral mediators were measured at the same time. RESULTS: The number of rolling leukocytes on the endothelium was significantly reduced in the treated mice (p < 0.01). The decrease of white blood cell and platelet counts was significantly inhibited in the treated animals (p < 0.01 for both). A comparison of the intercellular adhesion molecule-1 (p < 0.05), soluble tumor necrosis factor-alpha receptor (p < 0.05), and interleukin-6 (p < 0.01) levels showed less increase in the treated mice. CONCLUSION: Antithrombin showed a protective effects on the microcirculation of staphylococcal enterotoxin B-challenged mice by attenuating leukocyte-endothelial cell interaction. Suppression of adhesive molecule expression and cytokine production appears to play roles in this effect.

Animals↗
PubMed2003

[Disseminated intravascular coagulation].

Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by systemic formation of microthrombi and fibrin deposition in the vasculature. Cancer is one of the leading cause of DIC, which often complicates bleeding tendency and organ dysfunction. Even though DIC therapy is expectant, it is still important, since the bleeding tendency limits the quality of patients' life remarkably. Heparin, low molecular weight heparin, danaparoid, protease inhibitors for coagulation factors and antithrombin III are the choices for DIC. However, since the selection of the drugs is different depending on the basal disease, it is important to understand the pathophysiology of the individual situation. In general, protease inhibitors is recommended for 'fibrinolysis dominant DIC' like DIC associated with leukemia and terminal stage solid cancer, in contrast, danaparoid and antithrombin III are the first choice for 'coagulation dominant DIC' like sepsis. Supplement of concentrated platelets and fresh frozen should be limited for the patients whose primary disease can be controlled.

Disseminated Intravascular Coagulation↗
PubMed2003

[Effect and mechanism of orally administered leucovorin/5-fluorouracil on colon cancer].

UNLABELLED: Leucovorin (LV)/5-fluorouracil combination is one of the first-line forms of chemotherapy for colorectal cancer, and in this regimen it was recommended that 5-FU be infused continuously from the venous route. However, since this regimen limits the patients' ADL, oral administration is preferable. The purpose of this study is to elucidate the mechanisms of orally-administered LV/5-FU. MATERIAL AND METHODS: The Gastrostomy was performed, and 1 x 10(6) of colon 26 was transplanted subcutaneously in CDF1 mice. In the continuous administration group, either 10, 20, 40 mg/kg of 5-FU and 100 mg/kg of LV were continuously infused for 7 days following gastrostomy using a microinfusion pump (n = 6). In the single infusion group, either 10, 20, 40 mg/kg of 5-FU was infused once a day for 7 days after gastrostomy concomitant with LV (n = 6). The other 6 animals served as the control, and LV alone was infused in this group. Tumor volume, thymidylate synthase inhibition rate (TSIR), incorporation of 5-FU into RNA (F-RNA) and body weight were measured at the end of the treatment. During the experimental period, mice were given free access to chow and water. RESULTS: The tumor volume suppression rate was significantly higher along with the amount of 5-FU. However, there was no significant difference between continuous and single infusion groups. TSIR was higher in the continuous group at the dose of 20 and 40 mg/kg. In contrast, F-RNA was higher in the single group at the dose of 20 and 40 mg/kg. Significant body weight loss was not recognized in any group. CONCLUSION: From these data, single administration of 5-FU is more effective for RNA dysfunction. On the other hand, continuous infusion is more damaging to DNA duplication. In summary, since the mechanism of the antitumor effect differs with the administration method, it is important to understand this mechanism.

Administration, Oral↗
PubMed2002

Factor Xa-inhibitor (DX-9065a) modulates the leukocyte-endothelial cell interaction in endotoxemic rat.

Abnormalities of vascular endothelial function and coagulation play important roles in the development of septic organ dysfunction. DX-9065a is a novel Factor Xa inhibitor that is expected to modulate both coagulation and endothelial function. The purpose of this study is to examine the effect of DX-9065a on leukocyte-endothelial interaction. Rats were injected with 1.0 mg/kg of endotoxin simultaneously with saline, (placebo group), 0.3 mg/kg DX-9065a (low-dose group), or 3.0 mg/kg DX-9065a (high-dose group; n = 6 in each group). At 1 and 3 h after injection, the mesenteric microcirculation was observed under intravital microscopy. In addition, TNF, IL-6, alanine aminotransferase (ALT), blood urea nitrogen (BUN), and lactate levels were measured. The number of leukocytes adhering to the endothelium was significantly reduced in both the high-dose and low-dose groups (P < 0.05 for both, compared to the control group). A comparison of the cytokine levels showed that the peak levels in the treatment groups tended to be lower. Markers of organ damage also showed less increase in the treatment groups (P < 0.05 for both treatment groups compared to the control group). In summary, the Factor Xa inhibitor DX-9065a showed a protective effect on the microcirculation of endotoxemic rats by attenuating leukocyte-endothelial interaction. Although the mechanism for this effect could not be fully elucidated, suppression of both excessive coagulation and cytokine production appear to play a role.

Animals↗