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Objective: We evaluated the association between prehospital epinephrine administration by emergency medical services (EMS) and the long-term outcomes of out-of-hospital cardiac arrest (OHCA) with initial pulseless electrical activity (PEA) or asystole. Methods: We conducted a controlled, propensity-matched, retrospective cohort study by using Japan's nationwide OHCA registry database. We studied 110,239 bystander-witnessed OHCA patients aged 15–94 years with initial non-shockable rhythms registered between January 2008 and December 2012. We created 1–1 matched pairs of patients with or without epinephrine by using sequential risk set matching based on time-dependent propensity scores to balance the patients' severity and characteristics. We compared overall and neurologically intact survival 1 month after OHCA between cases and controls using conditional logistic regression models by category of the initial rhythm. Results: Propensity matching created 7,431 pairs in patients with PEA and 8,906 pairs in those with asystole. Epinephrine administration was associated with higher overall survival (4.49% vs. 2.96%; odds ratio [OR], 1.55; 95% confidence interval [CI], 1.30–1.85) but not with neurologically intact survival (0.98% vs. 0.78%; OR, 1.26; 95% CI, 0.89–1.78) in patients with PEA, and with higher overall survival (2.38% vs. 1.04%; OR, 2.34; 95% CI, 1.82–3.00) and neurologically intact survival (0.48% vs. 0.22%; OR, 2.28; 95% CI, 1.31–3.96) in those with asystole. Conclusions: Prehospital epinephrine administration by EMS is favorably associated with long-term neurological outcomes in patients with initial asystole and with long-term survival outcomes in those with PEA.

ACADEMIC EMERGENCY MEDICINE 2012; 19:782–792 © 2012 by the Society for Academic Emergency Medicine Abstract Objectives: This study aimed to investigate whether early epinephrine administration in out-of-hospital cardiopulmonary arrest (OHCA) patients was associated with improved outcomes and to address the selection bias inherent in observational studies (more severe cases are more likely to receive epinephrine). Methods: This was a retrospective analysis of prospectively collected population-based data of adult bystander-witnessed OHCA patients from a nationwide Japanese registry between January 2007 and December 2008. To address selection bias, those who attained early return of spontaneous circulation (ROSC) without epinephrine administration were excluded, leaving 49,165 patients in the analysis. The outcomes were intact neurologic survival, defined as survival with cerebral performance category score 1or 2, and any survival at 1 month or at discharge (whichever was earlier). The primary predictor was the time from the start of cardiopulmonary resuscitation (CPR) by emergency medical services (EMS) to first epinephrine administration, with early epinephrine defined as within 10 minutes. Results: Multivariate logistic regression analysis showed that cardiac origin OHCA patients who received early epinephrine (≤10 minutes) had significantly higher rates of intact neurologic survival (odds ratio [OR] = 1.39, 95% confidence interval [CI] = 1.08 to 1.78) and any survival (OR = 1.73, 95% CI = 1.46 to 2.04) than those who did not receive early epinephrine, after adjusting for potential confounders. Results for noncardiac OHCA patients were similar. Conclusions: Early epinephrine administration may be associated with higher rates of intact neurologic survival and any survival in adult bystander-witnessed OHCA patients. This article provides a potential method to address the selection bias inherent in observational studies that examine the effects of drug administration in OHCA patients.

Background Patients with blunt trauma to the liver have elevated levels of liver enzymes within a short time post injury, potentially useful in screening patients for computed tomography (CT). This study was performed to define the optimal cut-off values for serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in patients with blunt liver injury diagnosed with contrast enhanced multi detector-row CT (CE-MDCT). Methods All patients admitted from May 2006 to July 2013 to Teikyo University Hospital Trauma and Critical Care Center, and who underwent abdominal CE-MDCT within 3 h after blunt trauma, were retrospectively enrolled. Using receiver operating characteristic (ROC) curve analysis, the optimal cut-off values for AST and ALT were defined, and sensitivity and specificity were calculated. Results Of a total of 676 blunt trauma patients 64 patients were diagnosed with liver injury (Group LI+) and 612 patients without liver injury (Group LI−). Group LI+ and LI− were comparable for age, Revised Trauma Score, and Probability of survival. The groups differed in Injury Severity Score [median 21 (interquartile range 9–33) vs. 17 (9–26) (p

Linear polarized near-infrared irradiation around the stellate ganglia (Lizer-SGB) is thought to have a similar effect to stellate ganglion block (SGB), namely, a reduced effect on stress. The effect of Lizer-SGB on various hormone levels was examined. Six adult male volunteers received bilateral Lizer-SGB, and blood was collected before and after this treatment, followed by measurements of plasma adrenocorticotropic hormone (ACTH) and serum cortisol (CS), luteinizing hormone (LH), testosterone (TS), thyroid stimulating hormone (TSH), triiodothyronine (T3) and thyroxine (T4). On a different day, the same measurements were taken from volunteers in the absence of irradiation. The results showed that ACTH, LH, TS and T4 levels were similar in treated and non-treated groups, whilst CS levels decreased after Lizer-SGB. Although TSH and T3 levels decreased, their values were not changed as a specific effect of Lizer-SGB. The results obtained showed that Lizer-SGB has an effect similar to SGB, regarding ...

Objectives: Neoendothelialization by circulating endothelial progenitor cells has been a topic of recent research. The extent and scale of this process in humans is not well understood. We examined the extent of neoendothelialization of the aorta and peripheral arteries in the case of a patient who underwent peripheral blood stem cell transplantation for acute radiation syndrome. Methods: Human tissue samples from the aorta and peripheral arteries were obtained at autopsy. Endothelial cells were isolated, confirmed by von Willebrand factor immunostaining, and then subjected to fluorescent in situ hybridization analysis using X- and Y-chromosome specific probes to examine neoendothelialization by donor cells as possible in this case in which the donor and recipient were of different genders. Results: The aorta showed almost 25% of all endothelial cells to be replaced by donor-origin endothelial cells. The peripheral arteries were also replaced but to a lesser extent. Discussion: The present study provides evidence that peripheral blood is a source of endothelial progenitor cells in humans. Neoendothelialization of the aorta occurs to a significant extent under certain conditions suggesting the potential for exploitation of therapeutic neovascularization by transplantation of circulating endothelial progenitor cells.

Patient A who was exposed to a critical dose of radiation developed skin lesions throughout the body surface, gastrointestinal disorder with massive diarrhea and prominent bleeding, which caused severe loss in body fluids. Gastrointestinal bleeding due to the deteriorated intestinal mucosa was considered to be one of the major causes of death, although infection did not develop, possibly because of SDD and aseptic intensive care, until terminal stages. Patient A ultimately developed respiratory and renal failure in addition to skin exudate and gastrointestinal bleeding, and died of multiple organ failure on the 83rd day after exposure. The extreme unevenness of the dose distribution and the neutron versus y-ray component made the clinical manifestation very complicated. Initially, the mean absorbed dose was calculated as 16-20 GyEq for Patient A, mainly based on neutron-activated 24Na in the blood. However, a very recent calculation showed that the absorbed skin dose was highest at the upper-right abdomen reaching 61.8 Gy (27.0 as neutron plus 34.8 Gy as y-ray). The dorsal side was calculated to have received one eighth of the value of the abdominal side, and much smaller neutron component. His absorbed-dose distribution throughout the body was very inhomogeneous because of the closeness of the standing point to the mixing tank. Despite prolonged survival because of intensive care with massive fluids and blood transfusion, peripheral blood stem-cell transplantation, cultured skin-cell grafts, and the administration of cytokines for marrow, the patient was not saved. Restoration of the bone marrow function, prevention of skin fibrosis, radiation lung damage, and repair of gastrointestinal mucosa, and final recovery of the patient were elusive. Abundant personnel and resources were also a prerequisite to allow for the comprehensive and collective intensive care. A further understanding of the effects of high-dose radiation as well as the basic and clinical development of regeneration medicine are important issues for the future.

We studied the change in gap junctional intercellular communication (GJIC) on human umbilical vein endothelial cells (HUVEC) under hypoxia-reoxygenation (H-R) conditions by the fluorescence redistribution after photobleaching (FRAP) method. Confluent HUVEC monolayers were exposed to hypoxia (pO20.1%) for 12 hours, and then were returned to normal atmospheric conditions for reoxygenation. Contrast microscopic observation showed no significant changes in the morphology of the HUVEC at any times after H-R. Reoxygenation following hypoxia caused time-dependent decrease in GJIC, that is, GJIC reduction was induced after 2 hours and reached maximum at 4-6 hours which recovered to normal levels after 18 hours. Oxidant sensitive fluorescence dye assay revealed that the generation of intracellular free radicals increased during the first 2 hours after reoxygenation. Hydroxyl radical scavengers (MCI-186, DMSO) and an iron chelator (deferoxamine) abolished the reduction of GJIC due to H-R. However, SOD, catalase and probucol were essentially inactive on this reduction. These data suggest that ischemia-reperfusion injury may be caused by a functional defect of GJIC induced by reactive oxygen radicals.

Vascular endothelial cells (EC), communicating with one another across gap junctions, are usually made dysfunctional by hypoxia and reoxygenation (H/R); however, very limited information exists regarding the effects of H/R on the endothelial gap junctions. We investigated whether H/R interferes with endothelial gap junctional intercellular communication (GJIC). After human umbilical vein EC had grown to confluence, they were exposed to hypoxia (pO2 < 0.1%) for 12–16 h and then returned to normal atmospheric conditions for reoxygenation. At 0-, 2-, 4-, 6-h reoxygenation, GJIC was detected by means of a fluorescence recovery after a photobleaching technique. The results demonstrated that a GJIC reduction (about 20% less than that under normoxia) was induced after 2 h of reoxygenation; after 4 h of reoxygenation, it began to recover (to about 10% less than that under normoxia); and after 6 h of reoxygenation, GJIC was restored to the normal level. Calphostin C (1 × 10−7 mol/l), a specific protein kinase C inhibitor, partially inhibited the reduction in GJIC (resulting in a level about 10% less than that under normoxia), whereas the tyrosine kinase inhibitor genistein (10 µmol/L) completely blocked the reduction in GJIC. Vanadate (1.5 mmol/l), a tyrosine phosphatase inhibitor, amplified the inhibitory effect of H/R on GJIC (to about 40% less than that under normoxia). Immunofluorescence and immunoprecipitation showed that 2-h reoxygenation significantly stimulated tyrosine protein phosphorylation, and this phosphorylation event was obviously enhanced by vanadate. The results of Western blotting showed that the gap junctional protein connexin 43 (Cx43) was phosphorylated by H/R; moreover, immunoprecipitation demonstrated that 2-h reoxygenation induced a prominent increase of tyrosine phosphorylation of Cx43 compared with that under normoxia. These data indicate that H/R induces a transient endothelial GJIC dysfunction through the activation of tyrosine kinase and phosphorylation of tyrosine residues of Cx43. J. Cell. Physiol. 180:305–313, 1999. © 1999 Wiley-Liss, Inc.

To examine (1) the effects of trauma on changes in neutrophil L-selectin and CD11b expression and on the levels of soluble L-selectin and (2) whether these alterations are different on leukocyte subpopulations in those patients who develop multiple organ dysfunction syndrome.Twenty patients with Injury Severity Score (ISS)or = 16 and 15 patients with ISS score16 were studied. Arterial blood were collected serially after injury. The staining of leukocyte surface adhesion molecules was performed with antibodies against L-selectin and CD11b. Positive cell count and mean fluorescence intensity were determined by flow cytometry. Soluble L-selectin was measured using enzyme-linked immunosorbent assay.In patients with ISSor = 16, neutrophil L-selectin expression showed an immediate increase, reaching peak levels between 3 to 4 hours after injury (p0.05 vs. patients with ISS16), followed by a gradual decrease. Plasma levels of soluble L-selectin reached peak levels at 6 hours after injury. However, in patients with ISS16, minimal changes in L-selectin expression and soluble L-selectin were observed. Neutrophil CD11b expression showed an immediate increase for the first 3 hours followed by a gradual increase up to 24 hours after injury. In patients who developed multiple organ dysfunction syndrome, CD11b both on neutrophils and lymphocytes remained elevated for 120 hours.These findings suggest that acute neutrophil activation is an early event after trauma and may be implicated as "a vulnerable window" for leukocyte-mediated end organ injury.

This study aimed to investigate whether early epinephrine administration in out-of-hospital cardiopulmonary arrest (OHCA) patients was associated with improved outcomes and to address the selection bias inherent in observational studies (more severe cases are more likely to receive epinephrine).This was a retrospective analysis of prospectively collected population-based data of adult bystander-witnessed OHCA patients from a nationwide Japanese registry between January 2007 and December 2008. To address selection bias, those who attained early return of spontaneous circulation (ROSC) without epinephrine administration were excluded, leaving 49,165 patients in the analysis. The outcomes were intact neurologic survival, defined as survival with cerebral performance category score 1 or 2, and any survival at 1 month or at discharge (whichever was earlier). The primary predictor was the time from the start of cardiopulmonary resuscitation (CPR) by emergency medical services (EMS) to first epinephrine administration, with early epinephrine defined as within 10 minutes.Multivariate logistic regression analysis showed that cardiac origin OHCA patients who received early epinephrine (≤ 10 minutes) had significantly higher rates of intact neurologic survival (odds ratio [OR]=1.39, 95% confidence interval [CI]=1.08 to 1.78) and any survival (OR=1.73, 95% CI=1.46 to 2.04) than those who did not receive early epinephrine, after adjusting for potential confounders. Results for noncardiac OHCA patients were similar.Early epinephrine administration may be associated with higher rates of intact neurologic survival and any survival in adult bystander-witnessed OHCA patients. This article provides a potential method to address the selection bias inherent in observational studies that examine the effects of drug administration in OHCA patients.

1978年から1990年までの13年間に国立水戸病院救命救急センターでは50例の膵外傷手術例を経験した。主膵管損傷の有無と十二指腸損傷合併の有無によりI, II, III型に大別し,さらにII, III型を膵周囲主要血管損傷の有無よりそれぞれII a, II bおよびIII a, III bと2つに分けるという損傷形態分類を試みた。この分類は簡便で,形態別に手術術式とおよそ対応した。つまり,I型には膵縫合・ドレナージ,II型には膵体尾部切除,III型には膵体尾部切除,膵切離膵空腸吻合などの膵の処置に,十二指腸損傷の処置を加えればよいということである。また,この分類は死亡率からみた予後もよく反映した。手術術式は,膵縫合・ドレナージを30例(60%)に,膵切除術のなかでは膵体尾部切除を11例(22%)に,膵頭十二指腸切除を1例(2%)に,またRouxen-Yにて膵空腸吻合(Letton-Wilson法),十二指腸空腸吻合を合わせて7例(14%)に行った。膵外傷の治療は,その機能の保全より安全をより重視する基本方針をとっており,膵体尾部切除を11例(22%)と多用する傾向がみられた。膵損傷の際,膵切除量80%以下の体尾部切除に伴う糖尿病は11例中1例(9%)のみで,また消化吸収障害は1例もなかった。また,膵体尾部切除後の合併症発生頻度(36%)も縫合・ドレナージ術後の頻度(38%)と同程度であった。膵体尾部切除は簡便で手術時間が短縮でき,安全であり膵機能の面からも問題は少なく,膵断裂・挫傷例に基本術式とできると考えられた。全体として死亡率は16%,術後合併症率は42%であった。死亡例(8例)の検討では,その原因は膵周囲主要血管からの出血と術後のMOFであった。予後の改善のためには,損傷形態に基づいた適切な術式を選択することにより術後合併症の減少と受傷早期に膵周囲主要血管からの出血をコントロールすることが必要である。

Importance Neurologically intact survival after out-of-hospital cardiac arrest (OHCA) has been increasing in Japan. However, associations between increased prehospital care, including bystander interventions and increases in survival, have not been well estimated. Objective To estimate the associations between bystander interventions and changes in neurologically intact survival among patients with OHCA in Japan. Design, Setting, and Participants Retrospective descriptive study using data from Japan’s nationwide OHCA registry, which started in January 2005. The registry includes all patients with OHCA transported to the hospital by emergency medical services (EMS) and recorded patients’ characteristics, prehospital interventions, and outcomes. Participants were 167 912 patients with bystander-witnessed OHCA of presumed cardiac origin in the registry between January 2005 and December 2012. Exposures Prehospital interventions by bystander, including defibrillation using public-access automated external defibrillators and chest compression. Main Outcomes and Measures Neurologically intact survival was defined as Glasgow-Pittsburgh cerebral performance category score 1 or 2 and overall performance category scores 1 or 2 at 1 month or at discharge. The association between the interventions and neurologically intact survival was evaluated. Results From 2005 to 2012, the number of bystander-witnessed OHCAs of presumed cardiac origin increased from 17 882 (14.0 per 100 000 persons [95% CI, 13.8-14.2]) to 23 797 (18.7 per 100 000 persons [95% CI, 18.4-18.9]), and neurologically intact survival increased from 587 cases (age-adjusted proportion, 3.3% [95% CI, 3.0%-3.5%]) to 1710 cases (8.2% [95% CI, 7.8%-8.6%]). The rates of bystander chest compression increased from 38.6% to 50.9%, bystander-only defibrillation increased from 0.1% to 2.3%, bystander defibrillation combined with EMS defibrillation increased from 0.1% to 1.4%, and EMS-only defibrillation decreased from 26.6% to 23.5%. Performance of bystander chest compression, compared with no bystander chest compression, was associated with increased neurologically intact survival (8.4% [6594 survivors/78 592 cases] vs 4.1% [3595 survivors/88 720 cases]; odds ratio [OR], 1.52 [95% CI, 1.45-1.60]). Compared with EMS-only defibrillation (15.0% [6445 survivors/42 916 cases]), bystander-only defibrillation (40.7% [931 survivors/2287 cases]) was associated with increased neurologically intact survival (OR, 2.24 [95% CI, 1.93-2.61]), as was combined bystander and EMS defibrillation (30.5% [444 survivors/1456 cases]; OR, 1.50 [95% CI, 1.31-1.71]), whereas no defibrillation (2.0% [2369 survivors/120 653 cases]) was associated with reduced survival (OR, 0.43 [95% CI, 0.39-0.48]). Conclusions and Relevance In Japan, between 2005 and 2012, the rates of bystander chest compression and bystander defibrillation increased and were associated with increased odds of neurologically intact survival.

To investigate the effects of hemorrhagic shock and intra-abdominal hypertension (IAH) on inflammatory responses of peripheral circulating neutrophils such as intracellular cytokine production, phagocytic capacity and expression of nuclear factor (NF)- kappaB.Twenty-four rabbits were divided equally into 4 groups including a hemorrhagic shock (HS) group complicated by abdominal compartment syndrome (ACS) (Group A), a HS group (Group B), a ACS group (Group C) and a normal control group (Group D). Intracellular interleukin (IL)-8 production in the peripheral neutrophils were measured in the rabbits by flow cytometry, phagocytic function of the neutrophils evaluated by a chemiluminescence method and the NF-kappaB expression detected by immunocytochemistry before, immediately and 4 h after the traumatization.Four hours after the trauma, decreased intracellular IL-8 production and impaired phagocytic function of the peripheral neutrophils were observed in Group A along with suppressed NF-kappaB expression. But in Group B and Group C, the intracellular IL-8 production, phagocytic function and expression of NF-kappaB returned to the normal levels 4 hours after the trauma following the early-stage changes. In Group D, no significant changes occurred during the observation.Responsiveness and function of the neutrophils to the stimuli by endotoxin are suppressed by the sequential second-hit of IAH after hemorrhagic shock, which may contribute to the occurrence of sepsis in ACS.

Accidental exposure to acute high-dose total body neutron radiation is rare. We report a 35-year-old man exposed to a total body dose of 5.4 Gy neutron- and 8.5-13 Gy gamma-radiation in a radiation criticality accident. He received a blood stem cell transplant from his HLA-identical sister. There was bone marrow recovery with complete donor chimerism. Random chromatid breaks were observed in donor cells suggesting a bystander effect of neutron exposure. The subject died 82 days after the accident (75 days post transplant) from multi-organ failure.

We studied the change in gap junctional intercellular communication (GJIC) on human umbilical vein endothelial cells (HUVECs) under hypoxia/reoxygenation (H/R) conditions and the influence of leukocytes on GJIC by the fluorescence redistribution after photobleaching (FRAP) method. Contrast microscopic observations showed no significant changes in the morphology of the HUVECs after H/R. Reoxygenation following hypoxia (12 h) caused a time-dependent decrease in GJIC; that is, GJIC reduction was induced after 2 h and reached maximum levels at 4-6 h, recovering to normal levels after 18 h. The oxidant-sensitive fluorescence dye assay revealed that generation of reactive oxygen species (ROS) increased during the first 2 h after reoxygenation. Hydroxyl radical scavengers abolished reduction of GJIC by H/R. H/R led to significant release of membrane and supernatant tumor necrosis factor-α (TNFα). Anti-human TNFa antibody abolished the H/R-induced suppression of GJIC. GJIC of HUVECs that had adherent neutrophils was suppressed. Treatment with anti-human intercellular adhesion molecule-1 (ICAM-1) antibody abolished this suppression. Assays using intercell chambers showed that no suppression of GJIC was observed. This suppression was abolished by pretreatment with tyrosine kinase inhibitors. These data suggest that (1) ischemia/reperfusion injury may be involved in suppression of GJIC induced by TNFa release via reactive oxygen species; (2) suppression of GJIC by adherent neutrophils is mediated by ROS in HUVECs, not by proteases, and this suppression is attributed to tyrosine phosphorylation of gap junction protein caused by neutrophil adhesion through integrin and ICAM-1 binding.

Objectives To evaluate the effectiveness of pre-hospital adrenaline (epinephrine) administered by emergency medical services to patients with out of hospital cardiac arrest. Design Controlled propensity matched retrospective cohort study, in which pairs of patients with or without (control) adrenaline were created with a sequential risk set matching based on time dependent propensity score. Setting Japan’s nationwide registry database of patients with out of hospital cardiac arrest registered between January 2007 and December 2010. Participants Among patients aged 15-94 with out of hospital cardiac arrest witnessed by a bystander, we created 1990 pairs of patients with and without adrenaline with an initial rhythm of ventricular fibrillation or pulseless ventricular tachycardia (VF/VT) and 9058 pairs among those with non-VF/VT. Main outcome measures Overall and neurologically intact survival at one month or at discharge, whichever was earlier. Results After propensity matching, pre-hospital administration of adrenaline by emergency medical services was associated with a higher proportion of overall survival (17.0% v 13.4%; unadjusted odds ratio 1.34, 95% confidence interval 1.12 to 1.60) but not with neurologically intact survival (6.6% v 6.6%; 1.01, 0.78 to 1.30) among those with VF/VT; and higher proportions of overall survival (4.0% v 2.4%; odds ratio 1.72, 1.45 to 2.04) and neurologically intact survival (0.7% v 0.4%; 1.57, 1.04 to 2.37) among those with non-VF/VT. Conclusions Pre-hospital administration of adrenaline by emergency medical services improves the long term outcome in patients with out of hospital cardiac arrest, although the absolute increase of neurologically intact survival was minimal.

Accidental whole-body overexposure of radiation occurs very rarely. Radiation exposure causes DNA breaks in the cells and shows various clinical features, which are time dependent, dose dependent and tissue dependent. Neutron rays are more destructive than gamma rays but their actual effect on humans have been under-reported. We observed the time-dependent and the dose-dependent dermatological changes in a patient who was severely irradiated by neutron and gamma rays, with the aim of clarifying the clinicopathological features of severely irradiated skin. The detection of DNA breaks in keratinocytes was performed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling technique. The degenerative changes of the skin and the re-epithelialization varied in a time dependent and dose dependent manner. DNA breaks were significantly higher in irradiated keratinocytes. Neutron rays caused depth-dependent degeneration of the skin. Evaluation of DNA breaks in the skin cells might be a clue to estimate local dosimetry.