Ikuhiro Sakata

Epidemiology of childhood burns in the critical care medical center of Kinki University Hospital in Osaka, Japan.

The objective of the present study was to describe the characteristics of pediatric burns in order to prepare a program for the prevention of severe burn injuries in children. We conducted a retrospective study of burn victims aged 15 years or younger who were hospitalized in our Critical Care Medical Center between 1982 and 1997. There were 73 children with burn injuries hospitalized in our center during the study period. The greatest number were children 1 year old. The average % body surface area burned was 21. 5+/-20.5%. The most important causes of pediatric burns were found to be hot bath water and other hot liquids. Hot bath scalds accounted for about half of the pediatric burns occurring in all age groups, and they were often extensive. Non-bath scalds accounted for about one-third of the pediatric burns and were most frequent in children 2 years and younger. All the injuries sustained at home occurred when a family member was in the house. Similar to many reports from overseas, non-bath scalds were one of the most common causes of burns in this study; however, hot bath scalds were the most important cause. These data are being used to develop a prevention program. We also consider it necessary to educate children and their family members about the dangers of burn injuries.

Burns in a suicide attempt related to psychiatric side effects of interferon

A 50-year-old woman was admitted to our critical care center after pouring lamp oil on herself and setting herself on fire. Diagnosed with chronic hepatitis, she had received interferon-alpha at another hospital. During interferon therapy she developed anxiety, irritability, sleeplessness, and depression. At our hospital she underwent fluid resuscitation according to the method of Baxter. After treatment with topical cream and ointment, she underwent skin grafting. Interferon was not given. After discharge, wound healing proved satisfactory. She was intelligent and insightful, and her mental condition remained stable with no apparent emotional problems. As she had no significant past medical or psychiatric history and no history of substance abuse, we believe that her depression was a side effect of interferon therapy. A number of reports have described depression and other psychiatric disorders associated with interferon, but none of these accounts have concerned burns sustained in suicide attempts. This case underscores the potential seriousness of adverse reactions to interferon characterized by emotional disturbance and also illustrates that physicians who treat burn patients need to have an understanding of affective disorders and unusual side effects of medication.

Reduced acetaminophen-induced liver injury in mice by genetic disruption of IL-1 receptor antagonist

Acetaminophen (APAP) induced increases in intrahepatic expression of interleukin (IL)-1α, IL-1β, and IL-1 receptor antagonist (IL-1ra), when administered intraperitoneally. These observations prompted us to define the pathophysiological roles of IL-1ra in APAP-induced liver injury. Compared with wild-type (WT) mouse-derived hepatocytes, IL-1ra-deficient (IL-1ra KO)-derived hepatocytes exhibited more resistance against APAP but not APAP-derived major toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI). Moreover, the amounts of a major APAP adduct (selenium-binding protein), an indicator of NAPQI generation from APAP, was significantly lower in IL-1ra KO mice than WT mice with depressed intrahepatic expression of CYP1A2, CYP2E1, and CYP3A11, the enzymes crucially involved in NAPQI generation from APAP. These observations would indicate that IL-1ra deficiency impaired APAP metabolism. IL-1α and IL-1β were expressed to similar extents in livers of untreated IL-1ra KO and WT mice. By contrast, the intranuclear amount of p65 of NF-κB, which can suppress the gene expression of CYP1A2, CYP2E1, and CYP3A11, was higher in untreated IL-1ra KO than WT mice. Moreover, when mice were intraperitoneally administered APAP (200 mg/kg), IL-1ra KO mice exhibited attenuated APAP-induced liver injury as evidenced by reductions in serum alanine transferase levels and histopathological changes such as centrilobular necrosis, hemorrhages, and leukocyte infiltration. Finally, when given 12 h before APAP challenge, IL-1α repressed the intrahepatic expression of CYP1A2, CYP2E1, and CYP3A11, eventually reducing APAP-induced liver injury, along with reduction in APAP adducts. Collectively, NF-κB was activated without any stimuli by the genetic disruption of IL-1ra, and suppressed cytochrome P450 enzyme expression, thereby reducing APAP-induced liver injury.

Cytoskeleton‐modulating effectors of enteropathogenic and enterohemorrhagic Escherichia coli: a case for EspB as an intrinsically less‐ordered effector

Enterohemorrhagic and enteropathogenic Escherichia coli produce various effector proteins that are directly injected into the host‐cell cytosol through the type III secretion system. E. coli secreted protein (Esp)B is one such effector protein, and affects host‐cell morphology by reorganizing actin networks. Unlike most globular proteins that have well‐ordered, rigid structures, the structures of type III secretion system effectors from pathogenic Gram‐negative bacteria, including EspB, are often less well‐ordered. This minireview focuses on the functional relationship between the structural properties of these proteins and their roles in type III secretion system‐associated pathogenesis.

Characteristics of bath-related burns in Japan

A retrospective study of bath-related burn injuries was carried out at our institution. A total of 216 patients with burns were admitted between 1982 and 1996. Bath-related burns were identified in 58 patients (26.9%). The number of patients with bath-related burns increased throughout the study period. The percentage body surface area burned was 43.8 +/- 25.7% in the bath-related burn group and 27.3 +/- 28.3% in the bath-unrelated burn group. This difference was significant. There was no significant difference between the two groups with respect to mortality rate. The mechanism by which the patients sustained a bath-related burn clearly differed according to age. The percentage of burns which are bath-related and the severity of bath-related burns are higher in Japan than in any other country. This can be attributed to lifestyle, bathing systems, bathroom architecture, housing conditions and an increase in the elderly population. These burns can be prevented. Education based on this study will play a critical role in the prevention of the bath-related burn injuries.

Mesenteric venous thrombosis in a patient with congenital afibrinogenemia and diffuse peritonitis

Congenital afibrinogenemia is a rare autosomal recessive hemorrhagic disorder, and thrombotic complications occurring spontaneously or after infusion of fibrinogencontaining preparations have been reported in afibrinogenemic patients [1]. We report a case of mesenteric venous thrombosis due to fibrinogen replacement in a patient with congenital afibrinogenemia. A 19-year-old male with congenital afibrinogenemia had previously undergone uneventful surgical procedures for splenic rupture, intracranial bleeding, and mandibular abscess (2002) with preoperative supplement of fibrinogen concentrate. He was urgently admitted to the Critical Care Medical Center and diagnosed with diffuse peritonitis in 2003. After prophylactic administration of ten units of fresh-frozen plasma (FFP), resection of the small intestine was performed. Numerous thromboses were detected in the mesenteric veins of the resected specimen. The color of the remaining small intestine darkened during wound closure and mesenteric circulation worsened. Continuous infusion of unfractionated heparin (Novo Heparin 1000, Mochida Pharmaceutical Co., Japan) at 500 units/h was initiated following a 2000-unit bolus. The following day, massive resection of the small intestine, leaving only 60 cm of small intestine, was performed due to necrosis identified during a second-look operation. In 2004, emergency surgery was performed for adhesive intestinal obstruction without hemostatic complications by prophylactic administration of fibrinogen concentrate and unfractionated heparin. Perioperative laboratory data from 2002, 2003, and 2004 are shown in Table 1. In 2002, data revealed undetectable plasma fibrinogen levels by the functional assay, undetectable prothrombin time (PT) and activated partial thromboplastin time (APTT), and thrombocytosis. Supplementation with 9000 mg of fibrinogen raised fibrinogen levels to 1.91 g/l and normalized PT and APTT. In 2003, fibrinogen levels, PT, APTT, and platelet count after preoperative administration of ten units of FFP were approximately the same as in 2002. However, excessively high levels of hemostatic and inflammatory markers preoperatively indicated a hypercoagulable and inflammatory state. While perioperative heparin infusion in the first operation suppressed levels of hemostatic markers, the levels of those in the second-look operation were still above normal range. In 2004, preoperative tests again showed undetectable plasma fibrinogen level and PT, but APTT was normal. Values for all hemostatic markers, WBC, and C-reactive protein (CRP) were markedly elevated compared to reference ranges, but platelet count was normal. Supplementation with fibrinogen concentrate and intraoperative heparin administration resulted in a plasma fibrinogen concentration of 1.03 g/l and an APTT of 44.7 s. Fibrinogen level measured using both functional and immunological assays was 0.1 g/l at 5 days after administration of 1000 mg of fibrinogen concentrate. Prothrombin activation increases and increased thrombin generation has been observed in afibrinogenemia [2]. Thrombin represents a potent activator of platelets and platelet aggregation [3]. Tefferi et al. [4] reported marked thrombocytosis occurring in 22.0% of postsplenectomy patients. Furthermore, Remijn et al. [1] showed that the absence of fibrinogen results in large but loosely packed platelet aggregates and suggested that afibrinogenemic patients could be at risk for thrombosis. Thus, hypercoagulable states due to increased prothrombin activation and platelet aggregation may exist in our patient. Compensative reaction for severe intestinal inflammation and/or heparin-induced thrombocytopenia [5] may have been considerable for the reduced platelet count in 2004, Y. Takasugi (*) . Y. Shiokawa . R. Kajikawa . J. Oh . Y. Koga Department of Anesthesiology, Kinki University School of Medicine, 377-2 Ono-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan e-mail: yoshihiro.takasugi@nifty.com Tel.: +81-72-3660221 Fax: +81-72-3660206

Traumatic laceration of the intracranial vertebral artery causing fatal subarachnoid hemorrhage: Case report

A 36-year-old man who had been drinking alcohol had a fatal subarachnoid hemorrhage immediately after suffering a moderate craniofacial injury. Autopsy revealed a 3-mm longitudinal laceration of the left intracranial vertebral artery proximal to the posterior inferior cerebellar artery. There was no finding of arterial dissection. We discuss the mechanisms of the traumatic laceration of the vertebral artery in relation to traumatic dissection of the vertebral artery.

Molecular basis of actin reorganization promoted by binding of enterohaemorrhagic Escherichia coli EspB to α-catenin

EspB is a multifunctional protein associated with the type III secretion system of enterohaemorrhagic Escherichia coli, and interacts with various biomolecules including α‐catenin in the host cell. The binding of EspB to α‐catenin is thought be involved in actin reorganization during bacterial infection, although the precise mechanism of this phenomenon is still unclear. Recent research shows that dimerization of α‐catenin dissociates it from E‐cadherin/β‐catenin/α‐catenin complexes, and that the dimer suppresses Arp2/3‐mediated actin branching or polymerization. These results inspired us to evaluate the effect of EspB on the functions of α‐catenin. Based on a series of in vitro biochemical approaches, including pull‐down, co‐sedimentation and pyrene–actin polymerization assays combined with transmission electron microscopy, we conclude that EspB promotes all the functions of dimeric α‐catenin described above. These results clarified the molecular basis of reorganization of actin filaments during infection with enterohaemorrhagic Escherichia coli.

Molecular basis of actin reorganization promoted by binding of enterohaemorrhagic Escherichia coli EspB to alpha-catenin.

EspB is a multifunctional protein associated with the type III secretion system of enterohaemorrhagic Escherichia coli, and interacts with various biomolecules including α‐catenin in the host cell. The binding of EspB to α‐catenin is thought be involved in actin reorganization during bacterial infection, although the precise mechanism of this phenomenon is still unclear. Recent research shows that dimerization of α‐catenin dissociates it from E‐cadherin/β‐catenin/α‐catenin complexes, and that the dimer suppresses Arp2/3‐mediated actin branching or polymerization. These results inspired us to evaluate the effect of EspB on the functions of α‐catenin. Based on a series of in vitro biochemical approaches, including pull‐down, co‐sedimentation and pyrene–actin polymerization assays combined with transmission electron microscopy, we conclude that EspB promotes all the functions of dimeric α‐catenin described above. These results clarified the molecular basis of reorganization of actin filaments during infection with enterohaemorrhagic Escherichia coli.

The mRNA expression of fatty acid amide hydrolase in human whole blood correlates with sepsis

An excessive accumulation of anandamide (N-archidonoylethanolamine, AEA) is associated with septic shock. Results of previous studies have suggested that mRNA coding for the AEA degrading enzyme fatty acid amide hydrolase (FAAH), which converts AEA into arachidonic acid and ethanolamine, might be down-regulated in septic shock. We used real-time reverse transcription PCR assays to measure relative FAAH mRNA concentrations in the whole blood of 30 healthy donors and eight sepsis patients to ascertain whether such down-regulation takes place. Our results suggest that concentrations of FAAH mRNA in male and female samples from healthy donors are similar, but that concentrations are significantly lower in sepsis patients. These findings indicate that mRNA expression of FAAH in human whole blood correlates with sepsis, and may be an interesting biomarker for predicting the onset of septic shock.