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Biomedical subjects

Kaoru Koike

Publications and source records attributed to Kaoru Koike.

11 recordsLinked to original sources

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↗

Elevated plasma levels of fibrin degradation products by granulocyte-derived elastase in patients with disseminated intravascular coagulation.

Plasma levels of granulocyte-derived elastase (GE-XDP), D-dimer, and soluble fibrin (SF) were examined in 177 patients with disseminated intravascular coagulation (DIC) of various etiologies. Plasma levels of GE-XDP and D-dimer, but not SF, were significantly high in patients with sepsis and solid cancer. The ratio of GE-XDP/ D-dimer was significantly high in patients with trauma, burn, and sepsis, suggesting that fibrinolysis due to GE-XDP may be dominant in DIC. Plasma levels of GE-XDP and D-dimer, but not SF, were significantly high in patients with overt DIC and correlated with DIC score. Plasma levels of GE-XDP, but not SF, correlated significantly with D-dimer. Plasma levels of D-dimer, but not SF, correlated significantly with plasmin plasmin inhibitor complex (PPIC). Plasma levels of GE-XDP and D-dimer, but not SF, were significantly high in nonsurvivors. Plasma levels of GE-XDP, but not SF, correlated significantly with sepsis-related organ failure assessment (SOFA) score. These results suggest that GE-XDP is a potentially useful marker for the diagnosis of overt-DIC and as a predictor of organ failure-related outcome.

Biomarkers↗

Correlation of glomerular permeability, endothelial injury, and postoperative multiple organ dysfunction.

PURPOSE: To determine whether the degree of microalbuminuria correlates with the extent of endothelial cell injury, the severity of illness, and the magnitude of multiple organ dysfunction in patients who undergo emergency surgery. METHODS: We measured the urinary albumin : creatinine ratio (ACR) within 24 h after surgery in 31 patients and examined its relationship with various clinical measurements. RESULTS: The ACR increased during the first 24 h postoperatively. The log ACR correlated with the serum thrombomodulin concentration measured on the same day, but not with the level of plasma von Willebrand factor antigen. The increase in the log ACR correlated with the acute physiology and chronic health evaluation score (APACHE III), the simplified acute physiology score, the multiple organ dysfunction score, and the score of sequential organ failure assessment (SOFA) calculated on the same day, and the blood volume lost during the operation. The log ACR did not correlate with the white blood cell count or the serum C-reactive protein measured at the same time. The log ACR correlated with SOFA on postoperative days 3, 7, and 10, and mortality increased in accordance with the increase in log ACR. CONCLUSIONS: The urinary ACR correlated with the extent of endothelial cell injury, the severity of illness, and the magnitude of multiple organ dysfunction.

APACHE↗

Detection of circulating superantigens in an intensive care unit population.

OBJECTIVE: Plasma concentrations of superantigens were measured in an intensive care unit (ICU) population and the relationship of superantigen positive rates with the presence of sepsis was investigated. METHODS: Plasma samples were collected at least twice a week from 78 patients whose primary diagnoses were abdominal disorders (n = 27), respiratory disorders (n = 11), trauma (n = 10), burns (n = 10), cardiovascular disorders (n = 4), neurological disorders (n = 2), and others (n = 14). Five different species of superantigens, i.e., staphylococcal enterotoxins A, B, and C (SEA, SEB, and SEC), toxic shock syndrome toxin-1 (TSST-1), and streptococcal pyrogenic exotoxin A (SPEA), were measured using an enzyme-linked immunosorbent assay. RESULTS: Significant levels of plasma superantigens were detected in 16 patients. SEA was found in seven patients, SEB in four patients, SEC in two patients, TSST-1 in six patients, and SPEA in five patients. Superantigen detection rates were 6% (1/17) in patients without systemic inflammatory response syndrome (SIRS), 0% (0/21) in SIRS patients without infection, 31% (5/16) in septic patients without shock, and 42% (10/24) in septic shock patients. CONCLUSIONS: The presence of superantigens was confirmed in part of the ICU population. The role of superantigens in the pathogenesis of sepsis remains to be determined.

Adolescent↗

[Correlation between intravascular coagulation/fibrinolysis system and cytokines].

Bacterial factors stimulate the release of tissue factor as well as proinflammatory and antiinflammatory cytokines. TNF augments inflammation, TNF and IFN-gamma induce coagulation, and IL-1beta induces coagulation and fibrinolysis. IL-8 augments synergistic inflammation and coagulation. IL-6 augments coagulation and inhibits fibrinolysis. IL-10 inhibits inflammatory process and inhibits fibrinolysis. IL-4, IL-13, and TGF-beta act for anticoagulation. Administration of IL-2, G-CSF or IFN-gamma has been reported to have side effect of induction of coagulation. IL-12 induces coagulation first and fibrinolysis later. On the other, tissue factor induces proinflammatory (except TNF) and antiinflammatory cytokines, and thrombin enhances inflammation. Patients who died of SIRS/sepsis have been complicated with hypercoagulopathy and impaired fibrinolysis correlated with increased IL-10 production. Inhibition of IL-10 production or administration of fiblynolitic agents may be useful. Recently, activated protein C (APC) which has antiinflammatory effect has been paid attention in the treatment of SIRS/sepsis.

Aged↗

[Animal models for sepsis].

Despite promising preclinical evidence, dozens of new anti-sepsis agents have failed to demonstrate clinical efficacy. One of the reasons may be that the preclinical trials were conducted using animal models that did not adequately reflect clinical realities. Various kinds of experiments utilized for the development of new agents were carried where bolus or short term continuous infusions of large doses of bacteria or endotoxin were administered intravenously. For the preclinical testing of agents, (1) i.v. bacteria and endotoxin models in which the total challenge dose of adequate bacteria or endotoxin is reduced and/ or the length of administration time is increased, and (2) peritonitis models, e.g., cecal ligation and puncture and peritoneal implantation of bacteria or endotoxin, will become reasonable choices.

Animals↗

Comparison of diagnostic criteria for disseminated intravascular coagulation (DIC): diagnostic criteria of the International Society of Thrombosis and Hemostasis and of the Japanese Ministry of Health and Welfare for overt DIC.

We compared the criteria set by the International Society of Thrombosis and Hemostasis (ISTH) for the diagnosis of disseminated intravascular coagulation (DIC) with the criteria of the Japanese Ministry of Health and Welfare (JMHW) set for the diagnosis of overt DIC. We studied 1,284 Japanese patients with DIC. The rate of agreement in the diagnosis of DIC by the two diagnostic systems was 67.4%. In addition, only 2.0% of non-DIC patients by JMHW criteria were diagnosed with overt DIC by ISTH criteria, suggesting that ISTH for overt DIC includes typical cases of DIC. The concordance of diagnosis for DIC by ISTH and JMHW was significantly high in patients with trauma or acute promyelocytic leukemia. About 70% of DIC or overt DIC patients had more than 1 point in the scoring system for prothrombin time, but >50% of those patients had 0 point for plasma fibrinogen level. Abnormal fibrin and fibrinogen degradation product (FDP) levels and platelet counts were observed in >88% of DIC and overt DIC patients but were observed in >50% of non-DIC patients, indicating that these parameters are sensitive markers but not specific markers for the diagnosis of DIC. Considered together, our results suggest that the diagnostic criteria for DIC and overt DIC could be improved by changing the cut-off values of the global coagulation tests.

Blood Coagulation Tests↗

A randomized trial of postoperative UFT therapy in p stage I, II non-small cell lung cancer: North-east Japan Study Group for Lung Cancer Surgery.

OBJECTIVE: A prospective randomized trial was performed to investigate the prognostic advantage of postoperative adjuvant chemotherapy in patients with resected stage I-II non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: From March 1992 to December 1994, 221 patients with completely resected stage I-II primary NSCLC were enrolled and randomly assigned to two groups, as follows: 2-year oral administration of Uracil plus Tegafur (UFT) (adjuvant group, 109 patients), and surgical treatment alone (control group, 110 patients). RESULTS: The overall 5-year survival rates were 79% for the adjuvant group and 75% for the control group, and there was no statistical significance. The 5-year disease-free survival rates were 78% for the adjuvant group and 71% for the control group, and there was also no statistical significance. There have been seen no severe complications in the adjuvant group. The mean total dosages of UFT were about 75% of maximum basic amount. CONCLUSIONS: The UFT regimen was feasible. However, we have not observed any survival benefit in the adjuvant group. Larger trials are needed to confirm the effect of UFT to patients with resected NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗

[Animal models for sepsis].

When new immunomodulatory agents are developed for the treatment of sepsis, the efficacy is usually tested in animal models before going to clinical trials. However, despite promising preclinical evidence, dozens of new agents have failed to demonstrate clinical efficacy. One of the reasons may be that the preclinical trials were conducted using animal models that did not adequately reflect clinical realities. Various kinds of experiments utilized for the development of new agents were carried where bolus or short term continuous infusions of large doses of bacteria or endotoxin were administered intravenously. Massive i.v. bolus models using bacteria or endotoxin generally produce a rapid hypodynamic cardiovascular response with the animals dying within hours. The serum cytokine response is transient and is much greater in magnitude than that observed in septic patients. For the preclinical testing of agents, 1) i.v. bacteria and endotoxin models in which the total challenge dose of adequate bacteria or endotoxin is reduced and/or the length of administration time is increased, and 2) peritonitis models, e.g., cecal ligation and puncture and peritoneal implantation of bacteria or endotoxin, will become reasonable choices. The animals are also required to receive volume resuscitation and adjuvant antibiotic therapy.

Animals↗

[Pathophysiologies of ischemic/reperfusion injuries associating with hemorrhagic shock and up-to-date treatment].

During the ischemic state, hypoxanthine and xanthine oxidase are accumulated in the ischemic cells, and thereafter when oxygen is reperfused into ischemic cells, hypoxanthine and xanthine oxidase work to change oxygen into oxygen radicals. Oxygen radicals themselves damage various cells and they also injure cells by activating the transcription factors of inflammatory cells to induce special protein synthesis depending on individual cells. These processes are considered to be related to the systemic inflammatory response syndrome (SIRS) and multiple-organ dysfunction syndrome (MODS). Hemorrhagic shock is a generalized ischemic state and intestinal ischemia is more profound and more severely damaging than in other vital organs because of luxurious flow to the latter organs. The lack of microcirculation in large areas of the intestinal mucosa and in high-density areas of intestinal immune cells results in the synthesis of various inflammatory mediators, in the appearance of adhesion molecules, in the induction of tissue factors, and finally in the development of impairment of remote vital organs and MODS when oxygen is reperfused. There is no therapy for reperfusion injury after a prolonged ischemic state, and thus it is most important to reduce the intestinal ischemic time by supplying sufficient oxygen to preserve intestinal circulation and to commence early enteral nutrition. The development of new treatments to interrupt the vicious pathological cascade inducing MODS after ischemic reperfusion injury is mandatory.

Humans↗

Recombinant human interleukin-1alpha increases serum albumin, Gc-globulin, and alpha1-antitrypsin levels in burned mice.

The response to thermal injury is a complex physiologic process requiring communication between sites of injury and distant target organs. The liver, one of these target organs, synthesizes a family of secretory proteins, the acute phase proteins, that carries out specific immunoprotective functions. In this study we investigated the effects of daily recombinant human interleukin-1alpha (rhIL-1alpha) administration on the serum levels of negatively regulated, i.e., albumin and Gc-globulin and positively regulated, i.e., alpha1-antitrypsin, acute phase proteins in a murine model of thermal injury. Adult CF-1 female mice underwent a 6.5-seconds, 20% total burn surface area, full thickness steam injury, and received either intraperitoneal rhIL-1alpha (20 microg x kg(-1) x day(-1)) or diluent for 10 days. Seven and 14 days after injury, mice were sacrificed, and serum albumin, Gc-globulin and alpha1-antitrypsin levels were measured by crossed immunoelectrophoresis technique. Thermal injury significantly lowered serum albumin levels, tended to decrease Gc-globulin levels, and increased serum alpha1-antitrypsin levels. Daily rhIL-1alpha administration after burn injury prevented hypoalbuminemia, and increased serum levels of Gc-globulin and alpha1-antitrypsin. IL-1 therapy might be helpful to maintain the homeostasis and immunity of the host after thermal injury.

Animals↗