Analysis of protein S-100B in serum: a methodological study.

BACKGROUND: Dysfunction and damage of the human central nervous system can be detected with biochemical markers, and protein S-100B is the best-established such marker. The aim of this study was to evaluate whether the protein is stable during long-term storage, to establish reference values for the new Elecsys S100 test and to compare this new method with the Liaison Sangtec 100 test. METHODS: We analysed blood samples from 118 blood donors and 196 patients with subarachnoid haemorrhage or head injury. The long-term stability of S-100B in frozen serum samples was evaluated with repeated analysis in 1997 and 2003 using an immunoradiometric assay. Method comparison between the Liaison Sangtec 100 and Elecsys S100 tests was performed using Bland-Altman difference plots. RESULTS: Serum concentrations increased significantly during long-term storage (mean difference 0.15 microg/L; +/-2 SD, 0.55 microg/L). Serum measurements using the Elecsys S100 method in 118 healthy blood donors showed S-100B levels between 0.02 and 0.08 microg/L (mean 0.05). The 95th percentile was 0.07 microg/L. The Liaison Sangtec 100 test usually measured higher concentrations than the Elecsys S100 method, and the difference between the two methods increased with increasing concentrations. The mean difference between the methods was 0.14 microg/L (+/-2 SD, 0.39 microg/L). CONCLUSIONS: Protein S-100B is not stable during long-term storage and the two analytical methods are not interchangeable.     

重型颅脑损伤患者血浆S-100B蛋白测定的临床意义

目的　探讨血浆 S 10 0 B蛋白作为一种生物学指标在重型颅脑损伤诊断及预后判断中的应用价值。方法　重型颅脑损伤患者 6 6例 ,伤后早期 (2～ 6 h)抽取血浆标本 ,并从伤后 2 4 h起连续 3～ 7d检测血浆 S 10 0 B蛋白含量 ,将其结果与患者伤后 6个月格拉斯哥预后评分 (GOS)进行比较。结果　 6 6例患者中死亡 2 5例 ,致残 2 2例 ,良好 19例。死亡组 S 10 0 B平均 2 .6 0 μg/ L,明显高于存活组 (0 .5 5 μg/ L,P<0 .0 0 1) ;死亡组中有 14例 S 10 0 B峰值超过 2 .0 0 μg/ L,而存活组中只有 4例峰值超过 2 .0 0 μg/ L(P<0 .0 0 5 )。结论　血浆 S 10 0 B蛋白在重型颅脑损伤的诊断及预后判断中具有可靠的应用价值。     

Renal elimination of protein S-100beta in pigs with acute encephalopathy

BACKGROUND: Protein S-100beta is an established biochemical marker for cerebral injury in serum. For the further interpretation and possible use of S-100beta serum measurements in acute hepatic encephalopathy, renal elimination of S-100beta was measured in pigs with elevated S-100beta levels due to hepatic encephalopathy. METHODS: Eighteen female Norwegian Landrace pigs were randomly allocated to either hepatic devascularization (n=13) or sham operation (n=5). Repeated samples from the common carotid artery, right renal vein, and urine were simultaneously drawn for S-100beta analysis, using the Sangtec100 Liamat immunoassay. RESULTS: In hepatic devascularized pigs, arterial serum levels of S-100beta increased from 0.96+/-0.04 microg/L (mean +/- SEM) at t = 0h to 1.74+/-0.11 microg/L (mean +/- SEM) at t = 5 h. Urinary excretion increased simultaneously from 8.48+/-3.66 ng/h (mean +/- SEM) to 20.4+/-9.54 ng/h (mean +/- SEM), while renal arterial-venous fluxes for both kidneys increased from 1022+/-404 ng/h (mean +/- SEM) to 2444+/-590 ng/h (mean +/- SEM). CONCLUSIONS: Increased arterial S-100beta levels in pigs with acute hepatic encephalopathy are not a result of decreased renal elimination. The large difference between the renal arterial venous S-100beta concentrations and the urinary excretion of S-100beta indicate that renal metabolism is the major route of elimination.     

Multicenter evaluation of the analytical and clinical performance of the Elecsys S100 immunoassay in patients with malignant melanoma.

The aim of this multicenter study was to evaluate the technical and clinical performance of the Elecsys S100 electrochemiluminescence immunoassay and to assess its utility as a tumor marker in patients with malignant melanoma. Imprecision studies yielded within-run coefficients of variation (CVs) of 0.7-2.0% and between-day CVs of 1.0-6.4%. Serum samples that were distributed to 11 participating laboratories for a comparability analysis resulted in excellent recoveries of 93-105% related to the median for all laboratories. The functional sensitivity of the assay was determined to be below 0.02 microg/L. The lot-to-lot reproducibility of Elecsys S100 was tested by analyzing 110 sera with three different reagent lots on an E2010 analyzer. This lot-to-lot comparison showed excellent correlation, with a coefficient of 0.99. A 95th percentile cut-off value of 0.10 microg/L was calculated from values measured in 206 healthy individuals. Using this cut-off value, sensitivity of 41% was found, with positive and negative predictive values of 0.50 and 0.91, respectively. Method comparison with the Sangtec 100 luminescence immunoassay, run on two different analyzers, showed correlation with coefficients ranging from 0.76 to 0.95. A comparison of S100 values obtained with both tests showed identical patterns in 68 serial samples from 15 patients with malignant melanoma during follow-up. These findings indicate that serial measurements with the Elecsys S100 assay are useful for the follow-up and monitoring of therapy in patients with malignant melanoma.     

Significance of Elecsys S100 immunoassay for real-time assessment of traumatic brain damage in multiple trauma patients.

BACKGROUND: The neuroprotein S100 released into the circulation has been suggested as a reliable marker for primary brain damage. However, safe identification of relevant traumatic brain injury (TBI) may possibly be hampered by S100 release from peripheral tissue. The objective of this study was to measure early S100 levels using the Elecsys S100 immunoassay for real-time assessment of severe TBI in multiple trauma. METHODS: Consecutively admitted multiple trauma patients (injury severity score >or=16 points) were stratified according to the results of the initial cerebral computed tomography (CCT) examination. S100 serum levels were determined at admission and at 6, 12, 24, 48 and 72 h after trauma. Data were correlated to creatine phosphokinase (CK) and lactate dehydrogenase (LDH) serum levels. Using receiver operating characteristic (ROC) analysis, the discriminating power of S100 measurement was calculated for the detection of CCT+ findings. RESULTS: Median S100 levels of CCT+ patients (n=9; 37 years) decreased from 3.30 microg/L at admission to 0.41 microg/L 72 h after trauma. They revealed no significant differences to CCT- patients (n=18; 44 years), but remained elevated compared to controls. Median CK and LDH levels correlated with the corresponding S100 levels during the first 24 h after trauma. ROC analysis displayed a maximum area under the curve of only 0.653 at 12 h after trauma. No significant difference was calculated for the differentiation between CCT+ and CCT- patients. CONCLUSIONS: Measurements of S100 serum levels using the Elecsys S100 immunoassay are not reliable for the real-time detection of severe TBI in multiple trauma patients. Due to soft tissue trauma or bone fractures, S100 is mainly released from peripheral sources such as adipocytes or skeletal muscle cells.     

Results from a multicenter evaluation of the 4th generation Elecsys Troponin T assay

BACKGROUND AND OBJECTIVE: Discrepancies between serum and heparin plasma samples have been described for many commercial troponin assays including the cardiac troponin T (cTnT) assay. Using the current 3rd generation Elecsys Troponin T immunoassay, heparin plasma cannot be recommended for the determination of cTnT due to systematic lower test results caused by a direct interference of the immunoassay by heparin. The purpose of the multicenter study was to evaluate the analytical performance of an improved 4th generation Elecsys Troponin T immunoassay with a special focus on the comparability of cTnT results determined in heparin plasma and serum. METHODS AND RESULTS: The multicenter evaluation was performed in 10 clinical laboratories according to a standardized protocol (Roche Diagnostics, Penzberg, Germany, Study No. B05P008). The Elecsys Troponin T immunoassay was performed on the Modular Analytics E170 and Elecsys 2010 systems. Intraassay imprecision (n = 21) and total imprecision (2 runs/d, 10 days, triplicate measurements) were evaluated using 2 commercial controls (Roche Diagnostics) and 6 different serum pools (cTnT: 0.0140 - 4.102 microg/L). Intraassay CVs ranged from 0.73 to 3.22%. Total imprecision CVs ranged from 3.61 to 35.45% (cTnT < 0.1 microg/L) and 1.82 to 9.09% (cTnT > 0.1 microg/L), respectively. The cut-off for myocardial necrosis was determined to be 0.03 microg/L using the 10% total imprecision CV criteria. Linearity was assessed by serial dilutions of 6 different serum samples using cTnT negative serum pools. Linearity was proven up to 21.3 microg/L (recoveries: 90% - 110%). Regression data of all comparison studies were calculated according to the method of Passing and Bablok. The method comparison between the 4th generation and the commercially available cTnT immunoassay showed highly similar results across the whole measuring range (0.01 - 25.0 microg/L): y = 1.024x -0.001, r = 0.998; n = 988. Using the commercially available cTnT reagent, the serum to heparin plasma comparison yielded a systematic bias to approximately 8% lower cTnT results in heparin plasma. However, suitable comparability was obtained using the 4th generation Elecsys cTnT assay. The regression analysis (serum vs. heparin plasma) across the studied measuring range (cTnT: 0.01 - 14 microg/L) yielded the following equation: y = 0.975x + 0.001; r = 0.986; n = 403. However, rare individual serum to matched heparin plasma samples still yielded poor comparability (deviation > 20%) using the 4th generation Elecsys Troponin T immunoassay. CONCLUSION: Our data confirm an excellent analytical performance of the improved troponin T immunoassay. Most importantly, no systematic bias between cTnT results determined in serum and heparin plasma was observed from data obtained in 7 evaluation sites. The performance of the 4th generation Elecsys Troponin T assay is therefore comparable to other commercially available troponin immunoassays. Further studies are necessary to investigate the cause of poor comparability of cTnT results in rare individual serum to matched heparin plasma samples.     

Serum S-100B as an indicator of early postoperative deterioration after meningioma surgery

BACKGROUND: S-100B protein is an established serum marker of primary and secondary brain damage in head injury and stroke. Despite major progress in neurophysiologic monitoring, there are still difficulties in the early identification and quantification of evolving edema or trauma after craniotomy for tumor. In this study we aimed to correlate serum S-100B values with early postoperative neurologic course as well as late outcome in meningioma surgery. METHODS: We enrolled 50 consecutive patients who underwent meningioma resection. Serum S-100B was measured preoperatively and postcraniotomy for 7 consecutive days. Twenty-five patients (50%) developed immediate postoperative neurologic deterioration, and 15 (30%) had unfavorable 6-month outcomes. We used the Mann-Whitney U-test to assess the association of S-100B with all variables of interest. We used multiple logistic regression to search for the most significant predictor of postoperative deterioration. RESULTS: Increased S-100B was highly correlated with larger tumors, intraoperative difficulties, postcraniotomy acute deterioration, and long-term poor outcome. In addition, multiple logistic regression showed that age, sex, site, preoperative edema, history of meningioma resection, extent of resection, and histologic type did not correlate with postoperative increases in S-100B. Furthermore, patients with postoperative S-100B values >0.4 microg/L had increased risk of deterioration (relative risk = 9.0; 95% confidence interval, 2.4-34; P <0.0001) and of poor ultimate outcome (relative risk = 11; 95% confidence interval, 1.6-77; P = 0.002). CONCLUSIONS: After meningioma excision, postcraniotomy increases in serum S-100B appear to be an early indicator of short-term postoperative neurologic deterioration and of a poor longer-term outcome.     

Performance characteristics of six third-generation assays for thyroid-stimulating hormone

BACKGROUND: Thyroid-stimulating hormone (TSH) is used to detect primary hypo- and hyperthyroidism. Current guidelines for TSH assays recommend a functional sensitivity of < or =0.02 mIU/L. The protocol for determining the functional sensitivity of TSH assays specifies analyses of serum samples with two reagent lots over a 6- to 8-week period. METHODS: We determined the functional sensitivities of the Access 2, ADVIA Centaur, ARCHITECT i2000, E170, IMMULITE 2000, and Vitros ECi automated methods, using seven serum pools and two reagent lots for each method. RESULTS: The observed functional sensitivities were as follows: Access 2, <0.020 mIU/L; ADVIA Centaur, 0.039 mIU/L; ARCHITECT i2000, <0.005 mIU/L; Elecsys E170, 0.011 mIU/L; IMMULITE 2000, 0.014 mIU/L; Vitros ECi, 0.004 mIU/L. However, there were large differences between some method means for the seven serum pools. For the pool with the lowest TSH concentration, mean results were as follows: Access 2, 0.0203 mIU/L; ADVIA Centaur, 0.0085 mIU/L; ARCHITECT i2000, 0.0049 mIU/L; E170, 0.0098 mIU/L; IMMULITE 2000, 0.0077 mIU/L; Vitros ECi, 0.0014 mIU/L. Method-comparison studies using samples with TSH concentrations >0.2 mIU/L also showed method differences. The ARCHITECT i2000 method was the most precise at low TSH concentrations. CONCLUSIONS: TSH methods do not provide comparable results for serum pools with TSH concentrations <0.2 mIU/L or for patient results across the analytic measurement range. Further investigation into the cause of these differences and additional harmonization efforts are required.     

Measurements of serum S-100B protein: effects of storage time and temperature on pre-analytical stability.

Measurement of S-100B protein in serum or cerebrospinal fluid is increasingly used as a molecular marker of brain damage. However, there is no information about the pre-analytical in vitro stability of S-100B. We have investigated whether storing blood samples at different time periods and conditions affected the measured levels of S-100B protein. Blood samples were taken from 29 neurosurgical patients with normal serum S-100B values and from seven patients with increased serum S-100B values. Blood samples were immediately divided into nine aliquots for measuring S-100B immediately and after 4, 8, 12, and 24 hours, stored at room temperature or at 4 degrees C. Measurement of S-100B was performed using the LIAISON assay (Byk-Sangtec Diagnostica, Dietzenbach, Germany). Moreover, in 10 additional patients the effect of freezing the serum and thawing the sample after 24 hours was investigated. There were no differences between the results of S-100B measurements after storing the sample at different temperatures and time periods. There was no trend towards higher or lower values in all three groups. Therefore, blood samples may be collected as part of the daily clinical routine without time constraint and even stored overnight without affecting S-100B serum levels when measured with the LIAISON Sangtec 100 assay.     

S-100beta protein-serum levels in healthy children and its association with outcome in pediatric traumatic brain injury

OBJECTIVE: To describe normal serum levels of S-100beta in healthy children and determine whether serum S-100beta levels after traumatic brain injury are associated with outcome. DESIGN: Prospective cohort study. SETTING: Urban, tertiary care, children's teaching hospital. PATIENTS: A total of 136 healthy children and 27 children with traumatic brain injury. METHODS: Serum S-100beta levels were measured in 136 healthy children. A total of 27 children with traumatic brain injury had S-100beta levels collected within 12 hrs of injury. Other indices of severity of injury measured were admission Glasgow Coma Scale score, and Pediatric Risk of Mortality score at 24 hrs (PRISM 24). Outcome was measured by the Pediatric Cerebral Performance Category (PCPC) score at hospital discharge and 6 months postinjury or at death. MEASUREMENTS AND MAIN RESULTS: S-100beta levels in healthy children had a mean of 0.3 microg/L (90% confidence interval, 0.03-1.47) and inversely correlated with age, (r = -.32, p <.001). In children with traumatic brain injury, 6-month postinjury outcome inversely correlated with Glasgow Coma Scale score (r = -.47, p =.01) and correlated with PRISM 24 score (r =.83, p <.001) and S-100beta levels (r =.75, p <.001). Six months postinjury, comparing good outcome (PCPC < or = 3, n = 20) vs. poor outcome (PCPC > or = 4, n = 7), median admission Glasgow Coma Scale scores were 8 (range, 3-15) and 3 (range, 3-7, p =.01), median PRISM 24 scores were 7 (range, 0-19) and 30 (range, 18-35, p <.001), and median S-100beta levels were 0.85 microg/L (range, 0.08-4.8 microg/L) and 3.6 microg/L (range, 1.4-20 microg/L, p <.001), respectively. A serum S-100beta level of > or =2.0 microg/L is associated with poor outcome, with a sensitivity of 86% and a specificity of 95%. The area under the receiver operating curve for S-100beta was 0.94 (+/-0.05). CONCLUSIONS: Serum S-100beta levels in healthy children have a moderate inverse correlation with age. After traumatic brain injury in children, the acute assessment of serum S-100beta levels seems to be associated with outcome.     

Analytic evaluation of the beta-human chorionic gonadotropin assay on the Abbott IMx and Elecsys2010 for its use in doping control

OBJECTIVES: The principal objective of this study was to compare the analytical performance of the Elecsys2010 (Roche Diagnostics) system with the IMx (Abbott laboratories) system for beta-hCG assay in order to assess its possible utility as a confirmation test for the quantitative measurement of beta-hCG in urine for doping control purposes. DESIGN AND METHODS: Urine samples with spiked standard known concentrations of beta-hCG and different urine samples from athletes were used in order to determine the calibration curve stability and linearity, detection limit, total, within-run and between-run precision, and method comparison for the IMx and Elecsys2010 systems for beta-hCG assay, along with the stability of samples, at room temperature and at 4 degrees C. RESULTS: The IMx assay was linear up to 500 IU/L, whereas the Elecsys2010 assay was linear up to 1000 IU/L. The detection limit for the IMx and Elecsys2010 systems were 0.75 IU/L and 0.25 IU/L, respectively. The total precision of the IMx and Elecsys2010 systems were 相似文献   

Brain-specific NSE and S-100 proteins in umbilical blood after normal delivery

BACKGROUND: To determine normal blood levels of brain-specific proteins S-100 and neuron specific enolase (NSE) in healthy newborns and their mothers following uncomplicated birth. METHODS: Umbilical artery and vein blood and maternal venous blood was collected at 112 consecutive uncomplicated deliveries. Venous blood samples were taken from 18 of the neonates 3 days after birth. S-100 and NSE were analyzed quantitatively by double antibody immunoluminometric assay (Sangtec Medical AB, Sweden). RESULTS: Compared with adults, healthy neonates had higher levels of both S-100 and NSE. For S-100, median levels (range) were 1.10 microg/l (0.38-5.50 microg/l and 0.98 microg/l (0.43-2.70 microg/l) in umbilical artery and vein, respectively. For NSE, median levels (range) in umbilical artery blood and vein were 27 microg/l (10-140 microg/l) and 10.75 microg/l (8.80->/=200 microg/l) respectively. The maternal venous blood levels of both S-100 and NSE were significantly lower than in their infants. At 3 days of life, neonatal venous levels of the proteins were still high: S-100, 0.48-9.70 microg/l; NSE, 17->/=200 microg/l. In contrast to adults, haemolysis affected the S-100 levels in umbilical blood significantly. CONCLUSION: Concentrations of both S-100 and NSE in blood are greater in newborns after normal birth than in healthy adults. The higher levels in umbilical artery blood than in umbilical vein blood are consistent with a fetal origin of these proteins. High levels in venous blood at 3 days of life suggest that the high levels at birth are not related to the birth process but reflect a high activity of these proteins during fetal development.     

血清、脑脊液中S-100B、NSE水平与缺血性脑卒中的研究

目的探讨血清、脑脊液中S-100B、神经元特异性烯醇化酶(NSE)与缺血性脑卒中的关系。方法将无特定病原体(SPF)级48只SD大鼠随机编号分为8组,每组6只,手术后8 h做行为学评价。按照不同时间段,术后8 h、12 h、1 d、3 d、5 d、7 d、21 d腹腔取血及抽取脑脊液,检测S-100B蛋白及NSE水平;进行2,3,5-氯化三苯基四氮唑(TTC)大脑染色及行为学功能评价并分析其相关性。结果SD大鼠血清及脑脊液中S-100B及NSE在不同时间段呈趋势性变化;脑脊液中S-100B、NSE水平增高时间均早于血清中S-100B、NSE水平增高时间;脑损伤后12 h,脑脊液中NSE水平即可达到峰值,血清中S-100B、NSE水平增加,3 d后达到峰值,7 d后S-100B、NSE水平与对照组比较,差异无统计学意义(P>0.05);血清和脑脊液中S-100B、NSE水平与梗死面积、神经功能评分均呈正相关(P<0.05)。结论脑脊液及血清中S-100B及NSE均能反应脑损伤程度,作为缺血性脑卒中的生物学指标,可进一步为临床患者提供血液及脑脊液标本采集的时间窗口。     

Serum S100B levels in patients with neural tube defects

BACKGROUND: We investigated the levels of S100B protein in the serum of patients with neural tube defects (NTD), and the ontogenetic variation on this group of patients. METHODS: Samples from 24 control individuals and 25 patients with NTD were studied. S100B protein levels were determined using LIA-mat Sangtec kit. RESULTS: We observed no difference between the levels of S100B in NTD patients (median 0.860 microg/l) and control individuals (median 0.580 microg/l). When groups were classified according to age, decreased levels were observed in subjects > or = 4 y compared to the younger ones, on the control group; no significant difference was observed when the same comparison is performed on the group of patients with NTD. CONCLUSIONS: This study indicates that the serum concentration of S100B in patients with NTD is similar to that of normal individuals; however, patients with NTD do not show the negative correlation with age which was observed on normal individuals.     

新型丙型肝炎病毒抗体检测试剂Elecsys anti-HCV Ⅱ的性能评价与比较

目的评价新上市的丙型肝炎病毒抗体(抗-HCV)筛查试剂Elecsys anti-HCV Ⅱ的性能,并与其他两种临床上广泛应用的同类试剂进行性能比较。 方法使用罗氏Elecsys anti-HCV Ⅱ、雅培Architect anti-HCV和强生Vitros anti-HCV 3种试剂,平行检测4个HCV血清转换盘、861份临床常规样本、100份抗-HCV检测临界阳性样本及178份HIV感染患者样本。抗-HCV确诊试验为重组免疫印迹法(RIBA 3.0)或HCV RNA定量检测。此外,使用Elecsys anti-HCV Ⅱ检测203份不同HCV基因型样本以评价其基因型覆盖度。 结果相比Architect和Vitros anti-HCV,Elecsys anti-HCV II可提前7～14d检测到HCV感染后抗-HCV的产生;在检测临床常规样本(包括抗-HCV临界阳性样本)时,Elecsys anti-HCV Ⅱ有100%的敏感度及良好的特异度;70.22%(125/178)HIV感染患者样本为HCV RNA阳性,Elecsys anti-HCV Ⅱ可检测出其中97.60%(122/125)样本中的抗-HCV;Elecsys anti-HCV Ⅱ可能低估3b型样本的抗-HCV水平。 结论Elecsys anti-HCV Ⅱ可进一步缩短HCV感染后的检测窗口期,可灵敏、特异地检测临床样本包括免疫缺陷患者样本中的抗-HCV,适用于临床HCV感染的筛查,但对其检测特定HCV基因型样本的性能尚需纳入更多样本深入研究。     

Role of serum S100B as a predictive marker of fatal outcome following isolated severe head injury or multitrauma in males.

BACKGROUND: Severe traumatic brain injury (TBI) is associated with a 30%-70% mortality rate. S100B has been proposed as a biomarker for indicating outcome after TBI. Nevertheless, controversy has arisen concerning the predictive value of S100B for severe TBI in the context of multitrauma. Therefore, our aim was to determine whether S100B serum levels correlate with primary outcome following isolated severe TBI or multitrauma in males. METHODS: Twenty-three consecutive male patients (age 18-65 years), victims of severe TBI [Glasgow Coma Scale (GCS) 3-8] (10 isolated TBI and 13 multitrauma with TBI) and a control group consisting of eight healthy volunteers were enrolled in this prospective study. Clinical outcome variables of severe TBI comprised: survival, time to intensive care unit (ICU) discharge, and neurological assessment [Glasgow Outcome Scale (GOS) at ICU discharge]. Venous blood samples were taken at admission in the ICU (study entry), 24 h later, and 7 days later. Serum S100B concentration was measured by an immunoluminometric assay. RESULTS: At study entry (mean time 10.9 h after injury), mean S100B concentrations were significantly increased in the patient with TBI (1.448 microg/L) compared with the control group (0.037 microg/L) and patients with fatal outcome had higher mean S100B (2.10 microg/L) concentrations when compared with survivors (0.85 microg/L). In fact, there was a significant correlation between higher initial S100B concentrations and fatal outcome (Spearman's =0.485, p=0.019). However, there was no correlation between higher S100B concentrations and the presence of multitrauma. The specificity of S100B in predicting mortality according to the cut-off of 0.79 microg/L was 73% at study entry. Conclusions: Increased serum S100B levels constitute a valid predictor of unfavourable outcome in severe TBI, regardless of the presence of associated multitrauma.     

Elevated serum levels of S-100beta protein and neuron-specific enolase are associated with brain injury in patients with severe sepsis and septic shock

OBJECTIVE: We investigated whether serum levels of neuron-specific enolase (NSE) and S-100beta protein could be used to evaluate cerebral injury and to predict outcome in severe sepsis and severe septic shock. DESIGN: Prospective study. SETTING: University hospital. PATIENTS AND MEASUREMENTS: In 170 consecutively enrolled patients with severe sepsis and septic shock, serum S-100beta and NSE were measured daily during four consecutive days after intensive care unit admission. Admission Glasgow Coma Scale before sedation and daily Sequential Organ Failure Assessment scores were recorded in all patients. Acute encephalopathy was defined as either a state of agitation, confusion, irritability, and convulsions (type A) or characterized by somnolence, stupor, and coma (type B) and persistently observed during 72 hrs after withdrawing sedation. When clinically indicated, contrast computed tomography or magnetic resonance imaging were performed to evaluate brain injury. MAIN RESULTS: S-100beta and NSE increased in, respectively, 72 (42%) and 90 (53%) patients. High biomarker levels were associated with the maximum Sequential Organ Failure Assessment scores (p = .001), and the highest values were found in patients who died early, within 4 days of inclusion (p = .005). Low consciousness encephalopathy type B was more frequently observed in patients with elevated S-100beta (p = .004). S-100beta levels of >or=4 microg/L were associated with severe brain ischemia or hemorrhage, and values of <2 microg/L were found in patients with diffuse cerebral embolic infarction lesions. High S-100beta levels were associated with higher intensive care unit mortality (p = .04) and represented the strongest independent predictor of intensive care unit survival, whereas NSE and the Glasgow Coma Scale failed to predict fatal outcome. CONCLUSIONS: S-100beta and NSE are frequently increased and associated with brain injury in patients with severe sepsis and septic shock. S-100beta levels more closely reflected severe encephalopathy and type of brain lesions than NSE and the Glasgow Coma Scale.     

Relationship of thyroid function to post-traumatic S-100b serum levels in survivors of severe head injury: preliminary results

Objective To assess thyroid function abnormalities in survivors of severe head trauma and to examine their relationship with indices of brain injury severity.Design Prospective study.Setting General intensive care unit (ICU) in a university hospital.Patients and participants Twenty-two (21 men) head-injured patients, with a median age of 25.5 years at the time of injury, were investigated. Severity of brain trauma was assessed by Glasgow Coma Scale (GCS) score, Marshall Computerized Tomographic Classification, intracranial pressure levels and serum S-100b concentrations measured over a 6-day period.Interventions Thyroid function testing was performed 1 year after ICU discharge and included the measurement of free thyroxine, triiodothyronine and thyrotropin.Measurements and results On admission to the ICU, GCS ranged from 3 to 8. Peak S-100b was 1.49 µg/l (range: 0.37–5.26 µg/l). Median triiodothyronine and thyrotropin were 123 ng/dl and 1.60 IU/ml, respectively. Free thyroxine was 1.08±0.22 ng/dl (range: 0.7–1.5 ng/dl). Overall, 7 of the 22 patients (32%) had thyroid dysfunction. Four patients had central hypothyroidism and three patients had subclinical hypothyroidism. Peak S-100b correlated negatively with free thyroxine (r=–0.47, p=0.02). There were no correlations between other brain injury severity indices and thyroid hormone levels.Conclusions A significant subset of brain injury patients presents with changes in thyroid function 1 year after ICU discharge; these depend upon biochemical serum markers of head trauma severity.     

Impairment of blood-brain barrier integrity during carotid surgery as assessed by serum S-100B protein concentrations.

During carotid endarterectomy (CEA) the internal carotid artery is cross-clamped for a period of several minutes. This maneuver may cause cerebral hypoperfusion and/or impairment of the blood-brain barrier (BBB) even in cases where clinical signs are absent. The aim of the present study was to examine whether such alterations could be detected by monitoring the cerebral marker S-100B protein concentrations during and after CEA in the serum. Twenty-five consecutive patients (17 M/8 F, mean age: 64.2 years, range 47-79 years) undergoing elective CEA at our department were studied. All of these patients were without perioperative neurological deficit. Intraoperative samples were collected from internal jugular and peripheral venous blood: 1) before carotid cross-clamping; 2) immediately before declamping; 3) after clamp release. Postoperative samples were taken from peripheral blood at 6 and 24 h, respectively. S-100B was assayed in sera using an immunoluminometric technique. During carotid cross-clamping, S-100B protein concentrations in the ipsilateral jugular serum significantly (p < 0.02) increased to pre-clamp values. After declamping, however, S-100B returned to the baseline level. No differences were seen between the responses of hypertensive and normotensive patients. There was no correlation between carotid occlusion time and S-100B protein concentrations. In the peripheral venous serum no significant changes in S-100B concentrations were detected during or after CEA. We presume that the elevation of S-100B protein concentration during CEA in patients with no neurological deficits indicates the transient opening of the BBB elicited by carotid cross-clamping.     

Elevated serum levels of S-100B reflect the extent of brain injury in alcohol intoxicated patients after mild head trauma

Elevated systemic levels of S-100B are proposed as a potential indicator of brain damage in identifying high-risk patients after mild head trauma (MHT). Although incidence of alcohol intoxication is high in these patients, the influence of alcohol intoxication on S-100B levels is unclear. Therefore, the aim of our study was to investigate serum concentrations of S-100B in intoxicated (group 1) and sober (group 2) patients after MHT in comparison with those of mild (group 3) or severely intoxicated (group 4) individuals without trauma. S-100B was significantly increased in MHT patients exhibiting posttraumatic lesions in initial cranial computed tomography scan. Alcohol intoxication did not elevate S-100B levels in group 3 or 4 subjects. Our data indicate for the first time that alcohol intoxication does not influence the diagnostic value of S-100B measurements in patients after MHT.