Abstract: The aim of this study is to determine effective biochemical markers and optimal sampling timing for prediction of neurological prognosis in post-surgical aneurysmal subarachnoid hemorrhage (SAH) patients. Subjects were a sequential group of SAH patients admitted to our centre who underwent aneurysm clipping before Day 3 and who received a cerebrospinal fluid (CSF) drain. CSF samples from 32 patients were collected on Days 3, 7, and 14. Neurological outcome was assessed by neurosurgeons using the Glasgow outcome scale (GOS) at 6 months after onset. CSF levels of neuron-specific enolase (NSE), S100B, and glial fibrillary acidic protein (GFAP) were determined using enzyme-linked immunosorbent assay, and the CSF concentrations of malondialdehyde (MDA) were determined using spectrophotometric assay. In univariate analysis, S100B on Days 3 and 14, GFAP on Days 3 and 7, and MDA on Day 14 were significantly higher in the poor outcome group (GOS 1-4) than in the good outcome group (GOS 5). In multivariate analysis, only MDA on Day 14 was identified as a significant predictor of poor neurological outcome at 6 months after onset. The area under the receiver-operating characteristic (ROC) curve for MDA on Day 14 was 0.841. For a threshold of 0.3 microM, sensitivity and specificity were 0.875 and 0.750, respectively. Our findings suggest that these biochemical markers, especially MDA, show significant promise as predictors of neurological outcome in clinical practice.
Abstract: BACKGROUND:: Serum glial fibrillary acidic protein (GFAP) is a specific predictor of brain damage and neurologic outcome in patients with traumatic brain injury (TBI). In this study, serum GFAP, S-100B, and neuron-specific enolase (NSE) were compared in the same samples from severe trauma patients to assess their ability to predict abnormalities detectable on head computed tomography (CT). METHODS:: This study was a retrospective analysis at a single university emergency center. Thirty-four trauma patients were included. Serum samples were collected from the patients for 3 days. Serum GFAP, S-100B, and NSE concentrations were measured with enzyme-linked immunosorbent assays and compared in patients with and without TBI, as evaluated by head CT. RESULTS:: Serum GFAP, S-100B, and NSE were significantly higher in TBI patients than in the non-TBI patients (p < 0.05 for each protein). The receiver operating characteristic curves for TBI were compared for the three biomarkers for 3 days. Serum GFAP on day 1 had the largest area under the receiver operating characteristic curve (0.983), with 88.9% sensitivity and 100% specificity. CONCLUSIONS:: Serum GFAP has remarkable diagnostic value for TBI, defined by abnormal head CT findings, in prehospital-triaged patients with severe trauma.
Abstract: BACKGROUND: High-mobility group box 1 protein (HMGB1) is a nuclear factor that is a potent proinflammatory mediator, and may trigger increases in other inflammatory cytokines. The inflammatory cytokines in the cerebrospinal fluid (CSF) of patients with subarachnoid hemorrhage (SAH) have been reported previously, but HMGB1 has not. In this study, we measured HMGB1 and the inflammatory cytokines in the CSF of patients with SAH. METHODS: CSF samples were collected on days 3, 7, and 14 from the drainage tubes of the postaneurysm clips of 39 patients with SAH. HMGB1, interleukin-6 (IL-6), IL-8, and tumor necrosis factor alpha (TNF-alpha) were measured in the CSF, and compared between the patients with favorable (good recovery and moderate disability) and unfavorable outcomes (severe disability, vegetative state, and death) at 3 months. RESULTS: In the unfavorable outcome group, HMGB1 (P = 0.017), IL-6 (P = 0.003), IL-8 (P = 0.041), and TNF-alpha (P = 0.002) were significantly increased. HMGB1 correlated significantly with IL-6, IL-8, and TNF-alpha (R = 0.672, 0.421, and 0.697, respectively). CONCLUSIONS: HMGB1 was increased in the CSF of SAH patients with an unfavorable outcome, as were the other cytokines. These results suggest that HMGB1 and cytokines are related to the brain damage observed after SAH. HMGB1 might play a key role in the inflammatory response in the CNS of SAH patients.
Abstract: BACKGROUND: In past research, procalcitonin (PCT) and glial fibrillary acidic protein (GFAP) have been reported to be useful biomarkers in predicting neurological outcome after the return of spontaneous circulation (ROSC) following out-of-hospital cardiac arrest (CA), although they have only been studied separately. In this study, we compared the usefulness of PCT and GFAP in predicting neurological outcome. METHODS: This study was a retrospective, single-center analysis, conducted in the intensive-care unit of a university hospital. Twenty-one sequential post-CA patients were included. Serum samples were collected from patients at 12 and 24 h after ROSC. Serum PCT and GFAP were measured and compared in patients with favorable and unfavorable neurological outcomes, evaluated at 6 months using the Glasgow-Pittsburgh Cerebral Performance Categories. RESULTS: Serum PCT was significantly higher at 12 and 24 h in patients with unfavorable outcomes (P = 0.004 and 0.002, respectively). Serum GFAP was not significantly higher at 12 and 24 h in patients with unfavorable outcomes (P = 0.118 and 0.079, respectively). The combination of PCT and GFAP showed high predictive value for unfavorable outcomes (86.7% sensitivity and 100% specificity at 12 h; 100% sensitivity and 83.3% specificity at 24 h). CONCLUSION: Serum PCT is a marker of unfavorable neurological outcome in post-CA patients, and is superior to serum GFAP in the early phase.
Abstract: AIM OF THE STUDY: Serum glial fibrillary acidic protein (GFAP) has recently been identified as a specific predictor of brain damage and neurological outcome in patients with head trauma. In this study, serum GFAP was assessed as a predictor of neurological outcome in post-cardiac-arrest (PCA) patients. METHODS: This study was a retrospective, single-medical-center analysis, conducted in the intensive care unit of a university hospital. Forty-four sequential PCA patients with cardiogenic or non-cardiogenic arrest were included. The patients were treated with or without therapeutic hypothermia (TH). Serum samples were collected from the patients at 12, 24, and 48h after the return of spontaneous circulation (ROSC). Serum GFAP concentrations were measured by enzyme-linked immunosorbent assay and compared in patients with good and poor neurological outcomes, evaluated over a period of 6 months using Glasgow Outcome Scale. RESULTS: Serum GFAP was significantly higher in patients with a poor outcome at 12 and 24h without TH and at 48h with TH (P<0.05). GFAP (>0.1ngdL(-1)) was a specific predictor of poor neurological outcome at 6 months with or without TH treatment. CONCLUSIONS: Although this study is preliminary, serum GFAP after ROSC reflected a poor neurological outcome in PCA patients.
Abstract: AIM OF THE STUDY: In postcardiac-arrest (PCA) patients, hyperglycemia is a factor reflecting an unfavorable outcome, and might be caused by the inflammation and stress of "sepsis-like" syndrome. In this study, plasma glucagon, a representative glycogenolytic and gluconeogenic hormone, was measured and assessed the correlation for neurological outcome in PCA patients. METHODS: This study was a retrospective, single-medical-center analysis, conducted in the intensive care unit of a university hospital. Twenty-four sequential PCA patients were included. Plasma samples were collected from the patients on days 1, 2, and 3 after the return of spontaneous circulation (ROSC). Glucagon was compared in patients with favorable and unfavorable neurological outcomes. RESULTS: At all time points, plasma glucagon was significantly higher in patients with an unfavorable outcome (P<0.05). Glucagon on day 1 had remarkable sensitivity (88.2%) and specificity (85.8%) as an indicator of outcome, and correlated with the collapse-ROSC interval, the start of cardiopulmonary resuscitation (CPR)-ROSC interval, and the epinephrine dose during CPR. CONCLUSIONS: Plasma glucagon reflects unfavorable outcomes in PCA patients, and might be related to ischemic and reperfusion stress.
Abstract: This study used an electrochemical O2. sensor to investigate the effects of hyperoxia on generation of the superoxide radical (O2.) in the jugular vein during forebrain ischemia/reperfusion in rats. Twenty-eight male Wistar rats were allocated to a sham group (n = 7; sham-treated rats with inspired oxygen fraction [FiO2] 0.4), an HS/R group (n = 7; hemorrhagic shock without carotid artery occlusion and reperfusion with FiO2 0.4), a normoxia group (n = 7; forebrain ischemia produced by bilateral carotid arteries occlusion with hemorrhagic shock and reperfusion with FiO2 0.4), and a hyperoxia group (n = 7; forebrain ischemia with FiO2 0.4 and reperfusion with FiO2 1.0). The jugular venous O2. current was measured for 10 min during forebrain ischemia and for 120 min after reperfusion. The O2. current increased gradually during forebrain ischemia in the three groups other than the sham group. Immediately after reperfusion, the current showed a marked increase in the normoxia group and a pronounced decrease in the hyperoxia group. Levels of brain and plasma malondialdehyde, high-mobility group box 1 (HMGB1) protein, and intercellular adhesion molecule-1 (ICAM-1) were significantly attenuated in the hyperoxia group relative to those in the normoxia group.In conclusion, hyperoxia suppressed jugular venous O2. generation and malondialdehyde, HMGB1, and ICAM1 in the brain and plasma in the acute phase of cerebral ischemia/reperfusion. Thus, the administration of 100% oxygen immediately after reperfusion suppresses oxidative stress and early inflammation in cerebral ischemia/reperfusion.
Abstract: ABSTRACT: BACKGROUND: The hypothalamo-pituitary-adrenal (HPA) axis modulates the inflammatory response during sepsis. Macrophage migration inhibitory factor (MIF), which counteracts the anti-inflammatory activity of glucocorticoid (GC), is one of the mediators of the development of inflammation. An inflammatory imbalance involving GC and MIF might be the cause or result of adrenal insufficiency. Our objective was to clarify the relationship between serum MIF and adrenal function in the HPA axis of sepsis patients using the adrenocorticotropic hormone (ACTH) stimulation test. METHODS: An observational study was performed in a university intensive care unit over a two-year period. Of 64 consecutive sepsis patients, 41 were enrolled. The enrolled patients underwent an ACTH stimulation test within 24 h of the diagnosis of severe sepsis or septic shock. Clinical and laboratory parameters, including serum MIF and cortisol, were measured. RESULTS: Based on their responses to the ACTH stimulation test, the patients were divided into a normal adrenal response (NAR) group (n = 22) and an adrenal insufficiency (AI) group (n = 19). The AI group had significantly more septic shock patients and higher prothrombin time ratios, serum MIF, and baseline cortisol than did the NAR group (P < 0.05). Serum MIF correlated significantly with the SOFA (Sequential Organ Failure Assessment) score, prothrombin time ratio, and delta max cortisol, which is maximum increment of serum cortisol concentration after ACTH stimulation test (rs = 0.414, 0.355, and -0.49, respectively, P < 0.05). Serum MIF also correlated significantly with the delta max cortisol/albumin ratio (rs = -0.501, P = 0.001). Receiver operating characteristic curve analysis identified the threshold serum MIF concentration (19.5 ng/mL, P = 0.01) that segregated patients into the NAR and AI groups. CONCLUSIONS: The inverse correlation between serum MIF and delta max cortisol or the delta max cortisol/albumin ratio suggests that high serum MIF reflects an insufficient adrenal response in the HPA axis. Serum MIF could be a valuable clinical marker of adrenal insufficiency in sepsis patients.
Abstract: Acetamiprid belongs to a new class of insecticides called neonicotinoids, which have different effects from other insecticides. Neonicotinoids act as selective agonists at the nicotinic acetylcholine receptors, therefore their toxicity is higher to insect pests than to humans. Cases of acetamiprid poisoning are still rare, because neonicotinoids have been released in the market only within the last decade. We experienced a case of acute acetamiprid poisoning and measured the blood concentration of acetamiprid. A 79-year-old man had ingested acetamiprid and got medical attention two hours after ingestion. On arrival, he had consciousness disturbance (GCS-8), hypotension, nausea, vomiting and hyperglycemia, but had no constricted pupils nor mucous supersecretion which are characteristic in organophosphate poisoning. Gastric lavage was performed and activated charcoal and laxative were administered. Paroxysmal atrial fibrillation persisted until 11 hours after ingestion. The next day, his symptoms with regards to the effects of acetamiprid improved and he was discharged from the hospital without complication. Blood concentration of acetamiprid on arrival, approximately 2 hours after the ingestion, was 21.1 microg/ml.
Abstract: BACKGROUND: The Japanese Guidelines for the Diagnosis and Treatment of Deep-Seated Mycosis were established in 2003. Proven Candida infection (CI) is defined as at least one positive blood culture yielding a Candida species. Clinically documented CI requires documentation of more than 2 sites of colonization and a positive plasma beta-D-glucan test. Possible CI is diagnosed by one of the above criteria in febrile, nonneutropenic critically ill patients. OBJECTIVE: To assess the use of definitions of clinically documented and possible CI for guiding preemptive antifungal therapy in critically ill patients. METHODS: The patients treated in our intensive care unit (ICU) for at least 48 hours between 2000 and 2004 were investigated. The administration of antifungal agents and ICU mortality were compared among proven, clinically documented, and possible CI groups for age, sex, APACHE II score, diagnosis, length of ICU stay, treatment, number of colonization sites, and plasma beta-D-glucan level. RESULTS: Six patients were diagnosed with proven CI, 25 were diagnosed with clinically documented CI, and 104 with possible CI. The patients with clinically documented CI were compared with those with possible CI, and statistically significant differences were found in the following variables: APACHE II score (p = 0.018), length of ICU stay (p < 0.01), use of ventilator (p = 0.027), tracheotomy (p = 0.027), number of colonization sites (p < 0.001), plasma beta-D-glucan level (p < 0.001), and administration of antifungal agents (p < 0.001); incidence of mortality was not statistically significant (p = 0.33). The shorter length of ICU stay, use of ventilator, and continuous hemodiafiltration were risk factors for death after adjusting for APACHE II score, admission before/after 2003, antifungal therapy, and other factors. Although the frequency of the administration of preemptive antifungal therapy was higher after 2003 than before, the mortality rate did not differ significantly. CONCLUSIONS: The use of the definitions of clinically documented and possible CI may be beneficial for determining when it is appropriate to initiate preemptive antifungal therapy. However, use of the guidelines did not lead to prevention of possible CI proceeding to clinically documented CI or to improved mortality.
Abstract: Brain hypothermia therapy has been expected to lead to good neurological outcome in acute brain insults. There are a few positive results which have been proven by multicenter randomized clinical trials (RCT) in the cardiopulmonary arrest (CPA) in patients with ventricular fibrillation. Among these clinical trials, early application of hypothermia, maintenance of cerebral blood flow during hypothermia therapy and prevention of quick rewarming are pointed out to result in good outcome from clinical experiences. For brain hypothermia therapy to become an effective method for acute brain insults, indications, brain oriented intensive cares and biomarkers for the therapy must be established. RCT in acute brain insults beside CPA victims are needed in the near future.
Abstract: To clarify the involvement of intracellular signaling pathway and calpain in the brain injury and its protection by mild hypothermia, immunoblotting analyses were performed in the rat brain after global forebrain ischemia and reperfusion. After 30 min of ischemia followed by 60 min of reperfusion, Ca2+/calmodulin-dependent kinase II (CaM kinase II) and protein kinase C (PKC)-alpha, beta, gamma isoforms translocated to the synaptosomal fraction, while mild hypothermia (32 degrees C) inhibited the translocation. The hypothermia also inhibited fodrin proteolysis caused by ischemia-reperfusion, indicating the inhibition of calpain. These effects of hypothermia may explain the mechanism of the protection against brain ischemia-reperfusion injury through modulating synaptosomal function.
