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Biomedical subjects

H Nakae

Publications and source records attributed to H Nakae.

At least 19 recordsLinked to original sources

Failure to clear casts and secretions following inhalation injury can be dangerous: report of a case.

A 27-year-old man suffered smoke inhalation during a fire. Three days later, he complained of respiratory difficulty and was admitted to our hospital. Bronchoscopy revealed a very large buildup of sputum mixed with soot extending from the left main bronchus to the bifurcation of the upper and lower lobe bronchi and causing both pulmonary atelectasis and pneumonia. The debris was successfully removed the next day with basket forceps via bronchoscopy. The patient's airway pressure dropped significantly, enabling extubation almost immediately. Because of the possibility for respiratory failure caused by viscous secretion, it is important to perform initial bronchoscopy in cases of suspected inhalation injury.

Adult↗

Soluble products from Eikenella corrodens stimulate oral epithelial cells to induce inflammatory mediators.

In the inflammatory response elicited by bacterial colonization in periodontal pockets, pocket epithelial cells not only serve as a barrier to isolate the pocket microenvironment from external stimuli but also regulate the functions of neighboring cells including fibroblasts and inflammatory cells. To elucidate this mechanism, we characterized the effects of periodontopathic bacterium Eikenella corrodens 1073 components on the production of some inflammatory mediators in a human oral epithelial cell line (KB). In enzyme-linked immunosorbent assay (ELISA), the E. corrodens supernatant induced interleukin-6 (IL-6), IL-8 and prostaglandin E2 but not interferon-gamma (IFN-gamma) production by KB cells. After incubation with E. corrodens supernatant, KB cells showed a marked increase in the levels of IL-6, IL-8 and PG G/H synthase (cyclooxygenase)-2, but not IFN-gamma, gene expression by reverse-transcriptase polymerase chain reaction. All these E. corrodens products responsible for production of these inflammatory mediators resisted freezing and boiling and were present in a 10-kDa filtrate. These results imply that these soluble small-molecular-mass products from E. corrodens stimulate various inflammatory mediator productions by human oral epithelial cells and may play a role in the initiation of periodontal inflammation and subsequently perpetuate the inflammatory response during chronic infection.

Bacterial Adhesion↗

Effectiveness of combining plasma exchange and continuous hemodiafiltration (combined modality therapy in a parallel circuit) in the treatment of patients with acute hepatic failure.

Plasma exchange has gained widespread acceptance as an effective mode of blood purification in patients suffering from acute hepatic failure. However, it is still undetermined whether a single use of plasma exchange is capable of removing inflammatory cytokines completely or of preventing the development of citrate toxicity inherent with fresh frozen plasma. To clarify these issues we developed combined plasma exchange and continuous hemodiafiltration (CHDF) modality in which CHDF is performed in an opposite direction to plasma exchange. This study was designed to assess the effectiveness of combined modality therapy. Fifteen patients with acute hepatic failure were treated with plasma exchange (plasma exchange group) or plasma exchange and CHDF (plasma exchange + CHDF group), and various biochemical parameters were determined before and after treatment. Although citrate levels increased significantly after treatment compared with pretreatment levels in both the plasma exchange group and the plasma exchange + CHDF group, the percentage of the increase in citrate levels was significantly higher in the plasma exchange group than in the plasma exchange + CHDF group. Bilirubin levels were significantly lower after treatment in both the plasma exchange and plasma exchange + CHDF groups. There were no significant differences in tumor necrosis factor-alpha levels before and after treatment in the plasma exchange group, but they were significantly lower after treatment in the plasma exchange + CHDF group. Interleukin-6 (IL-6) levels increased significantly after treatment in the plasma exchange group, but there were no significant differences in the IL-6 levels before and after treatment in the plasma exchange + CHDF group. Interleukin-8 levels increased significantly after treatment in the plasma exchange group while decreasing significantly after treatment in the plasma exchange + CHDF group. These results indicate that combining plasma exchange and CHDF in a parallel circuit is an effective modality for suppressing the elevation of blood citrate levels and for removing inflammatory cytokines. This finding may have important implications for the development of an effective treatment for patients with acute hepatic failure.

Citrates↗

Soluble Fas and soluble Fas ligand levels in patients with acute hepatic failure.

PURPOSE: The Fas ligand (FasL)/Fas system is an apoptosis induction system that plays an important role in homeostasis and biophylaxis. We measured tumor necrosis factor alpha (TNF-alpha), soluble FasL (sFasL), and soluble Fas (sFas) in patients with acute hepatic failure to determine the relation between such failure and apoptosis. MATERIALS AND METHODS: We assayed 21 blood samples from patients with acute hepatic failure and 8 from patients with sepsis but without acute hepatic failure. Serum TNF-alpha, sFas, and sFasL levels were determined by enzyme-linked immunosorbent assay. RESULTS: sFasL levels were significantly higher in the patients with acute hepatic failure than in the patients with sepsis (0.68 +/- 0.42 ng/mL vs. 0 ng/mL, P =.0001). No significant differences were observed in sFas levels between the two groups. A significant correlation was observed between TNF-alpha and sFas levels (r = 0.657, P =.0008); a negative correlation was observed between TNF-alpha and sFasL levels (r = 0.454, P =.038). CONCLUSIONS: Our results suggest that pathologic aggravation of acute hepatic failure are related to changes in the FasL/Fas system and that TNF-alpha and sFasL, in particular, may play hepatoprotective roles.

Aged↗

Are proinflammatory cytokine concentrations reduced by plasma exchange in patients with severe acute hepatic failure?

We studied citric acid levels and proinflammatory cytokines (TNF-alpha, IL-6, and IL-8) before and after plasma exchange in 8 patients with acute liver failure. Plasma exchange was performed over a 6 to 7-hour period. At each session, 3.6 to 4.0 1 of plasma was exchanged for the same volume of fresh frozen plasma (FFP). The concentrations of citric acid were significantly increased after plasma exchange above concentrations before exchange (p<0.0001). There were no significant differences in TNF-alpha, IL-6, or IL-8 concentrations (p=0.7222, p=0.9357, p=0.6394, respectively). Thus, plasma exchange with FFP alone may not effectively remove cytokines.

Adult↗

Nitrite/nitrate (NOx) levels and hemodynamics during septic shock.

Nitric oxide (NO) acts as a vasorelaxant. We investigated the relationship between nitrite/nitrate (NOx), which are the final metabolites of NO, and hemodynamics during septic shock. We also examined tumor necrosis factor alpha (TNF-alpha), interleukin-8 (IL-8), and endotoxin. A significant negative correlation was observed between NOx levels and pulmonary capillary wedge pressure (PCWP; r = -0.6075, P = 0.0028). A significant positive correlation was noted between NOx levels and the cardiac index (CI; r = 0.5934, P = 0.0038). A significant negative correlation was found between NOx levels and the systemic vascular resistance index (SVRI; r = -0.4354, P = 0.0485). A significant positive correlation was observed between NOx levels and the stroke volume index (SVI; r = 0.5040, P = 0.0186). A significantly close positive correlation was also observed between TNF-alpha levels and NOx levels (r = 0.7848, P < 0.0001). These findings suggest that NOx levels are closely associated with hemodynamics during septic shock, resulting in a vascular relaxing effect.

Adult↗

Are nitrite/nitrate (NOx) levels elevated by inhalation injury?

The relationship between airway burn and nitric oxide (NO) levels in the early burn stage was investigated by quantifying nitrite/nitrate (NOx), which are the final metabolites of NO, in 22 burn patients. Although total body surface area (TBSA) and burn index (BI) were significantly higher in patients with airway-burn than in patients without airway burn (P=0.0347 and 0.0422, respectively), no significant difference in NOx levels was observed between the two groups (P=0.6196). The NOx levels were found to correlate significantly with TBSA (r=0.4775, P=0.0246). A significant correlation was also noted between the NOx levels and BI (r=0.4391, P=0.0409). These results suggest that NO reflects the intensity of inflammation in the early burn stage, but that excessive NO formation is unlikely to be induced by stress, such as that caused by airway burn.

Adult↗

Hyperemia of the intraperitoneal organs associated with scald burn.

A 65-year-old man with a history of cerebral infarction sustained scald burns over 54% of the body surface. In spite of adequate fluid therapy, respiratory management with an artificial ventilator, and continuous hemodiafiltration, the patient died on day 5 post-admission. Autopsy revealed necrotic change on the surface of the liver, and necrosis and perforation of the ileum. Histologic examination showed necrosis of the hepatocytes lining the surface and necrosis of the hepatocytes and congestion in the central area of the liver. We speculated that systemic responses to the extensive burn resulted in hyperemia of the intraperitoneal organs, thereby inducing acute liver failure and the subsequent development of multiple organ failure.

Aged↗

Bound and soluble adhesion molecule and cytokine levels in patients with severe burns.

We measured endotoxins, inflammatory cytokines and soluble adhesion molecules in the blood of 17 severe burn patients to determine the involvement of these factors in the pathophysiology of severe burns. All seventeen patients had burns with a total burn surface area of 20% or more and a burn index of 15% or more. Endotoxin was measured by an endotoxin-specific assay and tumor necrosis factor-alpha, interleukin 6 and interleukin 8 and soluble adhesion molecules were measured by enzyme-linked immunosorbent assay. CD11a, CD11b and CD18, measured by flow cytometry, were elevated in the non-surviving group, the septic shock group and the multiple organ dysfunction syndrome group, suggesting a close connection between these adhesion molecules and burns complicated by infection. Soluble adhesion molecules were found to indirectly reflect the level of endothelial cell adhesion molecules, suggesting that inflammatory cytokines may also be involved in their production.

Adult↗

Tumor necrosis factor-alpha and tumor necrosis factor receptor I, II levels in patients with severe burns.

Tumor necrosis factor alpha (TNF-alpha) and tumor necrosis factor receptor I and II (TNFRI and TNFRII) were studied in 24 burn patients who had a total burn surface area (TBSA) of 50.2 +/- 20.4%. Immediately after the injury, both the TNFRI and TNFRII levels correlated significantly with TBSA (r = 0.7344, P < 0.0001; r = 0.6074, P = 0.0012). The TNFRI and TNFRII levels immediately after the injury were significantly higher in the 11 patients who later died of their burns than in the 13 patients who survived (0.8 +/- 0.4 ng/ml vs. 1.8 +/- 0.7 ng/ml, P = 0.0002; 2.3 +/- 1.1 ng/ml vs. 4.5 +/- 1.6 ng/ml, P = 0.0009). The TNF-alpha levels immediately after the injury did not differ significantly between the group that survived and the group that died. The TNFRI and TNFRII values for the entire follow-up period also correlated significantly with TBSA. Peak TNFRI and TNFRII levels were significantly higher in the group that died than in the group that survived (6.0 +/- 4.7 ng/ml vs. 14.1 +/- 7.8 ng/ml, P = 0.0009; 7.0 +/- 5.1 ng/ml vs. 16.7 +/- 5.2 ng/ml, P = 0.0003). The TNF-alpha levels correlated significantly with both the TNFRI and the TNFRII levels. The TNFRI and TNFRII levels thus closely reflected the severity of the burns in both the acute postburn period and the subsequent follow-up period. In other words, these parameters well reflected the severity and outcome of the burns, irrespective of the presence or absence of accompanying infection.

Adult↗

Red blood cells attenuate sinusoidal endothelial cell injury by scavenging xanthine oxidase-dependent hydrogen peroxide in hyperoxic perfused rat liver.

AIMS/BACKGROUND: Rat liver perfused with an oxygenated buffered solution alone results in degenerative changes even when the perfusion flow is accelerated to give a sufficient oxygen supply. On the other hand, perfusion media supplemented with red blood cells (RBCs) preserve the viability of the liver. The present study was conducted to clarify how RBCs protect the isolated perfused liver. METHODS: The liver was perfused with and without RBCs in a perfusate equilibrated with supra-physiological oxygen tension at regulated inflow pressures, and controlled hepatic oxygen consumption. We examined alanine aminotransferase and purine nucleoside phosphorylase activity in the perfusate as specific markers of liver cells injury. Hydrogen peroxide (H2O2) production and morphological changes were determined using cerium electron microscopy. Apoptosis was detected by measuring CPP 32 protease activity and using TdT-mediated dUTP-digoxigenin nick end-labeling. RESULTS: When the liver was perfused with RBC-free buffer, H2O2 production and consequent injury progressing to apoptosis were initiated in the sinusoidal endothelial cells (SECs). After SECs were injured, H2O2 appeared in the hepatocytes. H2O2 production and associated degenerative changes were attenuated both morphologically and enzymatically by the addition of RBCs, a specific xanthine oxidase (XOD) inhibitor and the H2O2 radical scavenger, catalase. CONCLUSIONS: In the liver perfused with RBC-free buffer, H2O2 production and consequent injury were initiated in SECs. RBCs attenuate liver injury by scavenging XOD-dependent H2O2.

Alanine Transaminase↗

Electrolyzed strong acid aqueous solution irrigation promotes wound healing in a burn wound model.

The purpose of the study was to understand the effectiveness of electrolyzed strong acid aqueous solution (ESAAS) for acceleration of epithelialization in a rat burn wound model. Eighteen anesthetized Sprague-Dawley rats received 30% total body surface area third-degree burns, and 2 days after injury, the wound eschars were removed. Rats were divided into 3 groups: Group 1, no irrigation; Group 2, irrigation with physiological saline; and Group 3, irrigation with ESAAS. Wounds were observed macroscopically until they were fully epithelialized, and epithelialized wounds were examined microscopically. Epithelialization of the wounds occurred significantly early in the rats treated with ESAAS (p < 0.05). Proliferation of associated lymphocytes and macrophages was more extensive in all rats that underwent irrigation than it was in control rats. ESAAS irrigation may promote tissue growth in burn wounds.

Acids↗

Hydrogen peroxide induces midzonal heat shock protein 72 and apoptosis in sinusoidal endothelial cells of hypoxic rat liver.

OBJECTIVE: To investigate the heat shock protein (HSP) 72 expression and apoptosis induced by hydrogen peroxide in hypoxic rat liver. DESIGN: Prospective control study using the isolated rat liver. SETTING: Animal research facility. SUBJECTS: Fasted, pathogen-free specific, male Sprague-Dawley rats. INTERVENTIONS: A low-flow hypoxia model was made by reducing an afferent pressure from 10 to 2.5 cm H2O, and by perfusing the isolated rat liver for 2 hrs. MEASUREMENT AND MAIN RESULTS: We investigated the hydrogen peroxide production by using the 2'-7' dichlorofluorescein image, the induction of HSP 72 by using immunohistochemistry, and apoptosis by using terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling method in the low flow hypoxic rat liver. In low-flow hypoxia, hydrogen peroxide production, HSP 72 expression, and apoptosis were induced in the midzone of rat liver. Prevalence of HSP 72 expression was higher in the sinusoidal endothelial cells (SEC) than in the hepatocytes. All apoptotic cells were SEC with expression of HSP 72. Hydrogen peroxide was derived from hepatocytes. Pretreatment with the specific xanthine oxidase inhibitor, sodium(-)-8-(3-methoxy-phenylsulfinylphenyl) pyrazolo [1,5-a]-1,3,5-triazine-4-olate monohydrate significantly attenuated hydrogen peroxide production, HSP 72 expression, and apoptosis of SEC in the midzone. CONCLUSION: Xanthine oxidase-dependent hydrogen peroxide induces midzonal and SEC-dominant HSP 72 expression and apoptosis in hypoxic rat liver.

Animals↗

Effectiveness of electrolyzed oxidized water irrigation in a burn-wound infection model.

OBJECTIVE: The purpose of the study was to determine whether electrolyzed oxidized water (EOW) functions as a bactericide in burn injury with Pseudomonas aeruginosa infection in a rat burn-wound model. METHODS: Anesthetized Sprague-Dawley rats (n = 31) were subjected to third-degree burns to 30% of total body surface area. Two days after injury, all rats were infected with P. aeruginosa using 1 mL of a suspension containing 1 x 10(8) colony-forming units. Rats were assigned to one of three groups: no irrigation (group I), irrigation with physiologic saline (group II), or irrigation with EOW (group III). Blood culture, endotoxin levels, and survival rates were determined. RESULTS: Survival rate was significantly higher in group III than in groups I or II (p < 0.0001). Serum endotoxin levels on day 3 after infection in group III were significantly lower than the levels in group I (p < 0.01) and group II (p < 0.01). There were significant differences between the three groups in the culture of P. aeruginosa (p < 0.05). CONCLUSION: Irrigation and disinfection with EOW may become useful in preventing burn-wound sepsis.

Animals↗

Long-term follow-up study of unruptured vertebral artery dissection: clinical outcomes and serial angiographic findings.

OBJECT: Although the spontaneous occurrence of an unruptured vertebral artery (VA) dissection has increasingly been recognized as a relatively common cause of stroke, and the clinical aspects of this lesion have gradually been determined, its natural course remains obscure. The main goal of this study was to clarify the management protocol for this condition by examining serial angiographic changes in patients with unruptured VA dissections. METHODS: Seventeen patients with unruptured VA dissections, including 13 men and four women, were clinically and angiographically examined between 1993 and 1998. All patients were observed using serial angiography studies. The initial angiography examinations most frequently revealed stenotic lesions (appearance of a pearl-and-string sign or string sign) in eight (47.1%) of 17 cases. In 15 cases (88.2%), changes in the lesions were evident on follow-up angiography studies. Stenotic lesions resulted in occlusion in four cases, normalization in three, and subsequent formation of an aneurysm in one case, which was treated successfully by proximal occlusion of the affected vessel performed using a detachable balloon. Occluded lesions, which were initially observed in three patients, recanalized in two patients and remained unchanged in one patient. Fusiform dilation alone was demonstrated in three patients during the initial angiography session; these lesions became normalized or were unchanged on follow-up studies. Saccular aneurysms were observed in two patients. In one of these cases, proximal ligation of the parent artery was successfully performed because of subsequent aneurysm enlargement. A double lumen, which appeared in one patient with an extradural VA dissection, became occluded. Magnetic resonance T2-weighted imaging studies revealed infarction corresponding to the posterior circulation in seven cases. During long-term observation in this series, good or excellent recovery was obtained in 14 (87.5%) of 16 patients, and moderate or severe disability in two (12.5%); one patient was lost to follow up after the second angiography study. CONCLUSIONS: A follow-up angiography study must be performed during the early stage (within approximately 3 weeks after onset of symptoms) to confirm the formation or enlargement of an aneurysm, because such conditions may be amenable to surgical treatment. Unruptured VA dissection could otherwise be treated and followed conservatively. Although the majority of dissected lesions seem likely to stabilize within a few months, as evidenced on angiography, in some cases a longer observation period is required.

Adult↗

The effective removal of proinflammatory cytokines by continuous hemofiltration with a polymethylmethacrylate membrane following severe burn injury: report of three cases.

The serum levels of proinflammatory cytokines were investigated in three patients with severe burn injuries complicated by sepsis and pulmonary edema, who were treated with continuous hemofiltration (CHF) using a polymethylmethacrylate (PMMA) membrane. All patients had suffered burn injuries to more than 30% of their total body surface area (TBSA) and had burn indexes of 20 or more. Both interleukin (IL)-6 and tumor necrosis factor-alpha were detectable in one patient, while the serum IL-6 levels were elevated in the remaining two patients. The serum cytokines decreased 24 h after the initiation of CHF. Determinations of IL-6 in inflow and outflow blood samples as well as in the filtration fluid revealed that IL-6 was ultrafiltrated and/or adsorbed by the filter. Two of the three patients did not survive. Nevertheless, the results of this study indicate that since burn injuries are frequently associated with hypercytokinemia, the removal of cytokines by CHF with a PMMA membrane may be effective in the management of severe burn injuries.

Adult↗

Nuclear matrix protein levels in burn patients with multiple organ dysfunction syndrome.

In this study, we investigated multiple organ dysfunction syndrome (MODS) and nuclear matrix protein (NMP), which is an indicator for apoptosis, in burn patients. The subjects were 17 patients with a total burn surface area (TBSA) of 26% or more. Eight of them had MODS, and nine did not. Seven patients died, and 10 survived. The NMP value in the group with MODS (610 +/- 318 units/ml) was significantly higher than in the group without MODS (82 +/- 31 units/ml). The NMP values of the patients who died (645 +/- 326 units/ml) were significantly higher than in the group who survived (111 +/- 95 units/ml), and they rose significantly as the number of impaired organs increased. Our findings suggested that the NMP level in burn cases associated with MODS was higher when apoptosis developed and larger numbers of organs were impaired.

Adult↗