Yasufumi Asai

Direct Binding of Toll-Like Receptor 2 to Zymosan, and Zymosan-Induced NF-κB Activation and TNF-α Secretion Are Down-Regulated by Lung Collectin Surfactant Protein A

The lung collectin surfactant protein A (SP-A) has been implicated in the regulation of pulmonary host defense and inflammation. Zymosan induces proinflammatory cytokines in immune cells. Toll-like receptor (TLR)2 has been shown to be involved in zymosan-induced signaling. We first investigated the interaction of TLR2 with zymosan. Zymosan cosedimented the soluble form of rTLR2 possessing the putative extracellular domain (sTLR2). sTLR2 directly bound to zymosan with an apparent binding constant of 48 nM. We next examined whether SP-A modulated zymosan-induced cellular responses. SP-A significantly attenuated zymosan-induced TNF-α secretion in RAW264.7 cells and alveolar macrophages in a concentration-dependent manner. Although zymosan failed to cosediment SP-A, SP-A significantly reduced zymosan-elicited NF-κB activation in TLR2-transfected human embryonic kidney 293 cells. Because we have shown that SP-A binds to sTLR2, we also examined whether SP-A affected the binding of sTLR2 to zymosan. SP-A significantly attenuated the direct binding of sTLR2 to zymosan in a concentration-dependent fashion. From these results, we conclude that 1) TLR2 directly binds zymosan, 2) SP-A can alter zymosan-TLR2 interaction, and 3) SP-A down-regulates TLR2-mediated signaling and TNF-α secretion stimulated by zymosan. This study supports an important role of SP-A in controlling pulmonary inflammation caused by microbial pathogens.

Extracorporeal cardiopulmonary resuscitation for patients with out-of-hospital cardiac arrest of cardiac origin: a propensity-matched study and predictor analysis.

Objective:Encouraging results of extracorporeal cardiopulmonary resuscitation for patients with refractory cardiac arrest have been shown. However, the independent impact on the neurologic outcome remains unknown in the out-of-hospital population. Our objective was to compare the neurologic outcome following extracorporeal cardiopulmonary resuscitation and conventional cardiopulmonary resuscitation and determine potential predictors that can identify candidates for extracorporeal cardiopulmonary resuscitation among patients with out-of-hospital cardiac arrest of cardiac origin. Design:Post hoc analysis of data from a prospective observational cohort. Setting:A tertiary care university hospital in Sapporo, Japan (January 2000 to September 2004). Patients:A total of 162 adult patients with witnessed cardiac arrest of cardiac origin who had undergone cardiopulmonary resuscitation for longer than 20 minutes (53 in the extracorporeal cardiopulmonary resuscitation group and 109 in the conventional cardiopulmonary resuscitation group). Interventions:None. Measurements and Main Results:The primary endpoint was neurologically intact survival at three months after cardiac arrest. We used propensity score matching to reduce selection bias and balance the baseline characteristics and clinical variables that could potentially affect outcome. This matching process selected 24 patients from each group. The impact of extracorporeal cardiopulmonary resuscitation was estimated in matched patients. Intact survival rate was higher in the matched extracorporeal cardiopulmonary resuscitation group than in the matched conventional cardiopulmonary resuscitation group (29.2% [7/24] vs. 8.3% [2/24], log-rank p = 0.018). According to the predictor analysis, only pupil diameter on hospital arrival was associated with neurologic outcome (adjusted hazard ratio, 1.39 per 1-mm increase; 95% confidence interval, 1.09–1.78; p = 0.008). Conclusions:Extracorporeal cardiopulmonary resuscitation can improve neurologic outcome after out-of-hospital cardiac arrest of cardiac origin; furthermore, pupil diameter on hospital arrival may be a key predictor to identify extracorporeal cardiopulmonary resuscitation candidates.

Septic Thrombophlebitis of the Portal and Superior Mesenteric Veins as a Complication of Appendicitis: Report of a Case

Pylephlebitis is extremely rare and associated with high mortality, even in this modern era. It usually occurs secondary to infection in the region drained by the portal systems or in the structure contiguous to the portal vein. We report a case of septic thrombophlebitis of the portal and superior mesenteric veins (SMV) with multiple liver abscesses caused by acute appendicitis with an abscess of the mesoappendix. We performed appendectomy and successfully removed the thrombi using a Fogarty catheter. Postoperative histopathological examination confirmed a diagnosis of appendicitis and septic thrombophlebitis of the portal vein and SMV. The patient recovered completely with appropriate medical and surgical treatment.

Emergency Endovascular Stent-Grafting for Infected Pseudoaneurysm of Brachial Artery

Abstract.The use of covered stents in an infected field is controversial. It is generally recommended that infected aneurysms be treated using autografts or allografts. We report a case of infected brachial pseudoaneurysms that developed after medical debridement of a methicillinresistant Staphylococcus aureus (MRSA)-infected wound of the right arm and emergency brachial artery bypass-grafting using the saphenous vein, which was successfully treated by endovascular stent-grafting followed by antibiotic administration. The present case suggests that endovascular stent-grafting prevents rupture and occlusion of infected aneurysms and enables the continued administration of antibiotics.

Shortening of cardiopulmonary resuscitation time before the defibrillation worsens the outcome in out-of-hospital VF patients☆

OBJECTIVE The purpose of the study is to investigate the influence of cardiopulmonary resuscitation (CPR) time before the first defibrillation. METHODS The present study retrospectively analyzed the Utstein template records from April 1, 2002, to June 30, 2005. Patients who had out-of-hospital-witnessed cardiac arrest caused by cardiac disease and who presented with ventricular fibrillation (VF) as the initial cardiac rhythm were included in the study. Before April 1, 2003, the emergency medical technician (EMT) needed to obtain telephone permission before attempting defibrillation, and CPR was continued until permission was received (CPR first). On and after April 1, 2003, the EMT was immediately able to attempt a defibrillation without obtaining permission (shock first). RESULTS In 143 patients who had out-of-hospital-witnessed VF, 43 patients and 100 patients were treated with the CPR-first strategy and the shock-first strategy, respectively. The duration of CPR before the first defibrillation was longer in the CPR-first group than that in the shock-first group. The CPR-first group showed a higher rate of favorable neurologic outcome 30 days after (28% vs 14%; P = .048) and 1 year after cardiac arrest (26% vs 11%; P = .033) than those of the shock-first group. In the patients with witnessed VF, a stepwise multiple logistic regression analysis showed the CPR-first strategy to improve the neurologic outcome. CONCLUSIONS In patients with out-of-hospital-witnessed VF, sufficient CPR before the first defibrillation is considered to improve the neurologic outcome in comparison to the performance of immediate defibrillation.

A Proposed Universal Medical and Public Health Definition of Terrorism

The lack of a universally applicable definition of terrorism has confounded the understanding of terrorism since the term was first coined in 18th Century France. Although a myriad of definitions of terrorism have been advanced over the years, virtually all of these definitions have been crisis-centered, frequently reflecting the political perspectives of those who seek to define it. In this article, we deconstruct these previously used definitions of terrorism in order to reconstruct a definition of terrorism that is consequence-centered, medically relevant, and universally harmonized. A universal medical and public health definition of terrorism will facilitate clinical and scientific research, education, and communication about terrorism-related events or disasters. We propose the following universal medical and public definition of terrorism: The intentional use of violence--real or threatened--against one or more non-combatants and/or those services essential for or protective of their health, resulting in adverse health effects in those immediately affected and their community, ranging from a loss of well-being or security to injury, illness, or death.

Surgical influence on Th1/Th2 balance and monocyte surface antigen expression and its relation to infectious complications

Malignancy and operation for it cause several alterations in immune function that are considered to be concerned with the development of infectious complications. Forty-three patients who underwent curative surgery for gastrointestinal malignancies were entered into this study and were divided into two groups, those with and those without postoperative infection. Changes in the proportion of Th1/Th2 subsets in CD4+ T cells and the expression of human leukocyte antigen (HLA)-DR and CD16a molecules on monocytes were measured by flow cytometry before and after surgery. We performed intracellular cytokine stainings to exactly detect Th1/Th2 subsets. The proportions of interferon-γ-producing CD4+ T (Th1) cells in the preoperative state were almost equal in the two groups, and the proportion decreased on postoperative day (POD) 1 in both groups. On POD 7, the proportion of Th1 cells recovered to the preoperative level in the noninfection group, while the suppression was further reinforced in the infection group (26.8% versus 18.3%, p < 0.005). In contrast, the proportion of interleukin-4-producing CD4+ T (Th2) cells in the infection group (11.3%) was already suppressed in the preoperative state when compared with the noninfection group (17.3%, p < 0.005). Changes in HLA-DR and CD16a expression on monocytes were similar to the changes in the proportion of Th1 cells. These results indicate that the suppression of Th1 cell and monocyte functions during the early phase of the postoperative course was directly related to the occurrence of infectious complications and that several immunological impairments have already occurred in the preoperative state in cancer patients.

An experimental evaluation of the lactate concentration following mesenteric ischemia.

PurposeAlthough a diagnosis of mesenteric necrosis can easily be made, mesenteric ischemia is sometimes overlooked, especially in the acute phase. We experimentally evaluated the time course of the lactate concentration, which may be a possibly useful variable in making a diagnosis of mesenteric ischemia, and determined how an early diagnosis can be made.MethodsThe superior mesenteric artery (SMA) was surgically ligated in an anesthetized pig. Blood tests, including a blood gas analysis, were done using samples from the superior mesenteric vein (SMV), hepatic vein, femoral vein, and artery until 6 h after SMA ligation.ResultsThere were no variables in any samples that showed a significant change within 4 h after SMA ligation except for samples taken from the SMV. All acidosis-related variables had changed significantly within 6 h after ischemia. Among them, the lactate concentration only in the SMV was observed to have increased significantly within one hour after SMA ligation.ConclusionsCurrently available peripheral blood tests, including tests using blood obtained from the hepatic vein, do not enable the detection of mesenteric ischemia within 4 h after onset. In a case in which an exploratory laparotomy is performed, the measurement of the lactate concentration in SMV is thus considered to be a useful supplementary test for making a prompt diagnosis of mesenteric ischemia in an early phase.

Spinal cord ischemia after cardiac arrest

Subsequent to cardiac arrest, a 58-year-old man with intractable dysrhythmia and severe arteriosclerosis developed flaccid paraplegia, depressed deep tendon reflexes, and showed no pain or temperature sensation caudal to Th-7 in spite of completely intact proprioception and vibration sensation. An echocardiogram showed no clots or vegetation on the prosthetic valve and no thrombus in the left atrium or left ventricle. The patients paraplegia was permanent, at least through a follow-up period of 2 years. These findings suggest that the etiology was spinal cord ischemia due to blood supply in the area of the anterior spinal artery (ASA); however, magnetic resonance T2-weighted imaging demonstrated signal abnormalities throughout the gray matter and in the adjacent center white matter. Somatosensory-evoked potentials (SEP) measure neural transmission in the afferent spinal cord pathway, which is located in the lateral and posterior columns of the white matter; these showed a delay in latency between Th-6 and Th-7. The spinal cord is as vulnerable to transient ischemia as the brain. Spinal cord ischemia after cardiac arrest results from principal damage in the anterior horn of the gray matter, the so-called ASA syndrome; however, the pathways of SEP and pathogenesis of the spinal cord ischemia need further investigation.

Delayed Visceral Bleeding from Liver Injury After Cardiopulmonary Resuscitation

BACKGROUND Visceral injury is a life-threatening complication of cardiopulmonary resuscitation (CPR); however, the clinical significance has been masked by the lethal outcome of out-of-hospital cardiac arrest (OHCA). OBJECTIVE The objective is to share our experience of successful treatment of OHCA patients with serious, CPR-related visceral complications. CASE REPORTS We report two cases of cardiac-origin OHCA with liver injury exacerbated by heparinization during mechanical circulatory support. Although both patients presented with delayed massive liver bleeding (intrahepatic or peritoneal) that compromised hemodynamic status, one patient was successfully treated by selective transcatheter arterial embolization and the other by a surgical procedure. CONCLUSION Preventive measures such as careful CPR, as well as interventional or surgical repair after the early diagnosis of visceral injury, are required to improve the outcome in some cases of OHCA.