The type III secretion system is a recently identified mechanism for protein secretion in Gram-negative bacteria. Through this secretion system, bacteria directly translocate bacterial toxins into the cytosol of eukaryotic cells under direct contact with surface of the eukaryotic cells. The translocated proteins modify the eukaryotic cell signaling to evade host immunity. The type III secretion system was recently identified in Pseudomonas aeruginosa. P. aeruginosa secretes exoenzymes directly into the cytosol of the target cell through the type III secretion system. Cytotoxic P. aeruginosa that secretes the type III cytotoxins causes acute necrosis of lung epithelium, disseminates into the systemic circulation rapidly, and induces sepsis. It suggests the type III secretion system of P. aeruginosa has a major role in the pathogenesis of acute lung injury and sepsis in P. aeruginosa pneumonia.

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Patients with syncopal episode or ventricular fibrillation are usually referred for consultation to ICU. It has been recognized that ventricular fibrillation can occur in the structurally normal heart or so-called idiopathic ventricular fibrillation. In this category, an additional clinical and electrocardiographic subgroup, now frequently called Brugada syndrome, associated with a specific electrocardiogram (ECG) pattern of right bundle-branch block and ST-segment elevation in leads V₁ to V₃ was reported in 1992. Current management and prognosis based on several studies suggesting a high mortality risk for middle-aged men and implantation of a cardioverter-defibrillator (ICD) seems to be the only proven effective therapy in preventing sudden death in patients with the Brugada syndrome.
In the field of intensive and critical care medicine, the clinical features of the Brugada syndrome must be more widely enlightened, because it is possible to prevent sudden death.

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We examined whethar maintained cardiac output has benefical effect on neurological outcome evaluated about 6 months after traumatic brain injury (TBI) treated in moderate hypothermia of 32-33°C. Consecutive thirty one TBI patients were selected as a hypothermia group and serial 13 patients treated in 36.5-38°C were thought of as a control group. All patients had Glasgaw Coma Scale (GCS) less than or equal to 8 on admission and positive findings on CT scan. The hypothermia period was ususally three to four days and then patients were rewarmed at a rate of 1°C per day. There was no difference in age, gender, GCS score on admission and other indices between the groups. Cardiac output in hypothermic group was intentionally maintained in normal-hyperdynamic range by fluid loading and low dose dobutamine. The rate of the good outcome (GR, good recoverry+MD; moderate disability in GOS) was, however, significantly higher in hypothermic group than that of normothermic group (22/31 vs. 4/13; Chi-Square test, p<0.05). Although the effect of hypothermic therapy remains controversial, we insist that moderate hypothermia improves neurological outcome of TBI patients so far as their cardiac output was maintained in normal-hyperdynamic range.

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BACKGROUND: Intestinal mucosa have an important role in the protection against bacterial infiltration. Its injury could induce bacterial translocation, resulting in sepsis and/or endotoxemia. Induction of heat shock protein-70 (HSP-70) has shown cytoprotective effects acting as a chaperon of protein folding and assembly. Although sepsis may not only induce intestinal mucosal injury but also HSP-70 in mucosal tissue, the association of the cytoprotective effect of HSP-70 and intestinal injury during sepsis remains to be elucidated. The aim of this study is to clarify its association using septic rats.
METHODS: Sepsis was produced in rats by cecal ligation and puncture (CLP). Animals were divided into four groups: CLP, sham, heat-stress loading followed by CLP (HS-CLP), and sodium arsenite injection followed by CLP (SA-CLP) groups. Thirty-six hours after the operation, intestinal injury was histopathologically evaluated, and HSP-70 expression was studied by the immunohistochemical method.
RESULTS: HSP-70 was induced in the intestinal tissue of the CLP group but not in the sham group. The grade of intestinal injury in the HS-CLP and SA-CLP groups were reduced compared to that in the CLP group (P<0.05).
CONCLUSION: Sepsis induced HSP-70 in intestinal tissue, but its expression did not show cytoprotection. Induction of HSP-70 before CLP could reduce intestinal injury. These results indicate that HSP-70 has a cytoprotective effect on intestinal tissue against sepsis.

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To clarify the relevant factors to the tolerance for continuous sedation by midazolam and flunitrazepam with or without propofol, multifactorial retrospective observational case-controlled study was introduced. The subjects were 70 critically-ill patients admitted to ICU of our critical care and emergency center from June 1995 to January 1998. We examined the differences in clinical variables between 14 patients resisting continuous sedation (R group) and 56 patients successfully sedated with standard-dose sedatives (non-R group).
Patients in R group experienced significantly longer stay in ICU, longer mechanical ventilation, more prevalence of systemic inflammatory response syndrome (SIRS), more flunitrazepam as a choice of sedative, more continuous renal replacement therapy, and longer use of steroid and erythromycin than non-R group. We speculate, from these results, that strong inflammation or infection may lead to develop pharmacokinetic tolerance for sedative within a few days and long duration of mechanical ventilation accompanied by long-term sedation may lead to develop the pharmacodynamic tolerance in late phase about two weeks after. Further prospective study will determine the clinical risk factors of tolerance for sedative drugs.

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We treated a case of acute respiratory failure due to a postoperative fistula between right main bronchus and mediastinal abscess by drainage and extracorporeal membrane oxygenation. The patient was a 54-year-old male who underwent esophagotomy for esophageal cancer. On the 5th postoperative day, P/F ratio decreased to 47 because of a large amount of intratracheal pus. As differential lung ventilation failed to improve it, veno-venous extracorporeal membrane oxygenation was started at 2.2l·min^-1. The ventilator settings during the extracorporeal support were adjusted to maintain percutaneous oxygen saturation not less than 95% with F_IO₂≤60%. Bronchofiberscopy on the 9th postoperative day recognized a fistula communicating right main bronchus and mediastinal abscess. A 7.5Fr catheter was inserted into the abscess cavity through the tracheal tube and a fistula, and an 18Fr drainage tube was percutaneously inserted. Respiratory failure was improved in accordance with a reduction of pus. The patient was successfully weaned from the extracorporeal support on the 13th day, and then from a ventilator on the 40th day.

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We report selective impairment of the acetylcholine-induced vasodilation in the right arm of a patient with right hemiparesis due to old cerebral infarction. A 45-year-old male admitted due to recent myocardial infarction has a history of cerebral infarction evidenced by magnetic resonance imagings disclosed T1 low and T2 high signals in the left middle cerebral artery region at age 33, which was followed by sensory loss to pain, temperature, vibration and touch on his right side. Coronary angiography showed total occlusion of the left anterior descending artery and no stenosis on the right coronary or the left circumflex arteries. The vascular endothelial function was studied concurrently by measureing blood flow change in accordance with acetylcholine infusion compared with normal saline. Blood flow of the circumflex artery was 18.3ml·min^-1 during normal saline infusion. Acetylcholine administered at 0.45, 4.5 and 45μg·3min^-1 increased blood flow in a dose-dependent manner to 22.4, 35.7, 44.1ml·min^-1, respectively. Blood flow in the left brachial artery (neurologically normal side) was 108.2ml·min^-1 during normal saline infusion, and was dose-dependently increased to 122.3, 135.9, and 164.1ml·min^-1 by acetylcholine infusion at the rate of 22.5, 45, and 90μg·3min^-1. In contrast acetylcholine failed to increase blood flow in the right brachial artery (neurologically impaired side). It was 54.8 ml·min^-1 during normal saline and was 56.0, 54.0, and 60.9ml·min^-1 during the acetylcholine infusion at 22.5, 45 and 90μg·3min^-1. We conclude that central sensory disturbance may decrease endothelial response to acethylcholine in the affected limbs.

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A 24-year-old male, habitual thinner sniffer, and suffering polyuria and mascle weakness was admitted to our institute after sniffing thinner for several weeks.
The data on the admission day indicated severe hypokalemia, severe metabolic acidosis with normal anion gap, and high urinary level of hippuric acid which is a metabolite of toluene, a major component of thinner. Although the function of acidifying urine was not fully damaged, toluene-induced tubular injury in both proximal as well as distal tubes caused renal tubular acidosis (RTA). The proximal type RTA inhibits reabsorption of HCO₃^- and the distal type, on the contrary, inhibits active excretion of H⁺. Thus either acid loading such as NH₄Cl or low HCO₃^- concentration can acidify urine in the proximal type RTA.
Acid loading test done on the 25th admission day suggested our case to be the proximal type. Proximal type RTA is rarely reported so far as we reviewed but should be kept in mind of the physicians who take care.

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Nephrotoxicity is one of the most serious adverse effects of immunosuppresive agents and it may interfere with the anti-rejection therapy following organ transplantation. Human atrial natriuretic peptide (hANP) is known to have renal protective properties to accerate urine production, the mechanisms of which are attributable to dilatation of renal arteries and relaxation of messangial cells. By infusing hANP we successfully treated three cases of serious acute renal failure which were refractory to the conventional therapies. These results suggest that hANP is a possible additional modality for acute renal failure following organ transplantation.

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Gene therapies and oligonucleotide decoy (NFκB DON) therapy are recently tried, experimentally and clinically, in critical diseases without particular therapies. Acute severe pancreatitis, frequently treated in emergency wards and intensive care units, is one of these disorders with poor prognosis. We examined, as a preliminary study, if a gene therapy is effective in a cerulein-induced pancreatitis model in rats. In eleven male Sprague-Dawley rats, weighning 200 to 240g, pancreatitis was induced by subcutaneous injection of cerulein after pretreatment by NFκB DON (n=5), NFκB non-sense (NFκB NON, n=3), or saline (Control, n=3). After two hours, serum amylase and lipase levels were measured as severity indicators of pancreatitis. Serum amylase and lipase levels of NFκB DON group were significantly lower than NFκB NON and saline control group. Pretreatment of NFκB DON, which regulates genes by combining with NFκB in m-RNA level, partially suppressed acute pancreatitis in a rat model. This result suggests that the agent may be a new treatment for acute pancreatitis. Its effectiveness and its side effects in posttreatment should be further studied.

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