Serum neuron-specific enolase as a predictor of short-term outcome and its correlation with Glasgow Coma Scale in traumatic brain injury

Elevated serum neuron-specific enolase levels are correlated with brain cell damage. Low scores according to Glasgow Coma Scale are also considered as serious poor prognostic factor. The aims of the study were to investigate whether there is a correlation between the two measurements in patients with traumatic brain injury and whether serum neuron-specific enolase levels have potential as a screening test to predict outcome. A total of 169 consecutive patients with traumatic brain injury admitted to our clinic between 2002 and 2005 are included in this study. Those patients, who had any major health problem before trauma, were excluded from the study. However, patients with isolated head injury were included in the study. Serial serum neuron-specific enolase concentrations taken at the first 2, 24, and 48 h after traumatic brain injury were analyzed. A computed tomography was performed on each patient on admission. Their Glasgow Coma Scale scores were recorded serially. The relationship between Glasgow Coma Scale scores and the serum neuron-specific enolase levels were assessed by statistical methods. There was a significant negative correlation between the serum neuron-specific enolase levels and Glasgow Coma Scale scores. The levels of neuron-specific enolase were significantly higher in the patients who died in 30 days after trauma and whose scores were lower than or equal to 8 points in Glasgow Coma Scale. Although there are several serious limitations of the use of neuron-specific enolase as a biomarker in traumatic brain injury (i.e., hypoperfusion, extracranial trauma, bleeding, liver, or kidney damage also increase the level of neuron-specific enolase), its concentrations may be useful as a practical and helpful screening test to identify neurotrauma patients who are at increased risk and may provide supplementary estimation with radiological and clinical findings.     

Increased HLA-A*11 in Chinese children with steroid-responsive nephrotic syndrome

Human leukocyte antigen (HLA) associations have been frequently reported in childhood steroid-responsive nephrotic syndrome (SRNS) in other populations. The aim of this study was to characterize the immunogenetic background of Singaporean Chinese patients with childhood SRNS. We determined the HLA class I (HLA-A* and HLA-B*) as well as class II (HLA-DRB1*, HLA-DQB1*) gene polymorphisms using the polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) technique, in patients with SRNS (n=64) and normal controls (n=236 for HLA-A*, n=80 for HLA-B*, HLA-DRB1* and HLA-DQB1*). The frequency of HLA-A*11 allele was significantly higher in the SRNS patients compared to controls (78.1% vs 54.2%, respectively; relative risk, RR=3.01, Pc=0.011). However, there was no significant difference in the allele frequencies of HLA-B*, HLA-DRB1* and HLA-DQB1* between the SRNS patients and controls, unlike that in previous studies. Our data suggest that the immunogenetic background of Singaporean Chinese with childhood SRNS was different from that in other populations. As HLA-A*11 has been strongly associated with other autoimmune diseases, it is conceivable that the HLA-A*11-specific motif may play a role in the development of the abnormal T-cell-mediated immune response that may be responsible for triggering the proteinuria seen in SRNS. Received: 24 April 2001 / Revised: 14 November 2001 / Accepted: 18 November 2001     

Clinical stage T1c prostate cancer: pathologic outcomes following radical prostatectomy in black and white men

BACKGROUND: The incidence of prostate cancer in black men is 50% to 70% higher than among age-matched white men. Black men have a twofold higher mortality rate and overall tend to have higher serum prostate-specific antigen (PSA) levels than white men. To determine whether racial differences exist in men whose prostate cancer was diagnosed based solely on an elevated serum PSA level, we compared clinical and pathologic features in black and white men undergoing radical prostatectomy (RP) for clinical stage T1c prostate cancer. METHODS: We used a prospectively collected database to identify all men undergoing RP for clinical T1c prostate cancer between July 1995 and October 2000. A total of 129 consecutive men (56 black men and 73 white men) were compared for age at diagnosis, serum PSA level, biopsy Gleason score, pathologic stage, RP specimen Gleason score, incidence of lymph node metastasis, and incidence of positive surgical margins. RESULTS: Statistically significant differences were not found by race in patients' ages, serum PSA levels, biopsy Gleason score, pathologic stage, incidence of lymph node metastases, or incidence of positive surgical margins. The RP specimen Gleason score was more heterogeneous in black men than white men (P=0.02). CONCLUSIONS: Racial differences in the incidence and mortality rate of prostate cancer are well known, but differences in the clinical and pathologic features between black and white men with prostate cancer identified solely based on an elevated serum PSA level with negative results on digital rectal examination (clinical stage T1c ) have been poorly studied. Our results suggest that men with clinical stage T1c prostate cancer have similar clinical and pathologic findings regardless of race. These results suggest that early-detection programs using serum PSA testing for prostate cancer in black men potentially can result in improvements in prostate cancer outcomes in this high-risk group.     

血清游离和总前列腺特异抗原测定在鉴别前列腺良恶性病变中的价值

目的　比较血清总前列腺特异抗原 (TPSA)和游离PSA(FPSA)与TPSA的比值 (F/T)鉴别诊断良性前列腺增生 (BPH)和前列腺癌 (PCa)的价值。　方法　测定 177例BPH和 6 0例PCa患者血清TPSA、FPSA浓度 ,计算F/T值 ,分别比较F/T值与TPSA在诊断灰区、灰区外低值区及灰区外高值区中鉴别两种疾病的能力。　结果　在诊断灰区外高值区 ,TPSA和F/T在两组间的差别均有显著性意义 (0 .0 1

0 .0 5 ) ,而F/T值的差别有显著性意义 (P <0 .0 5 ) ,假阴性率仅 3% ;在灰区外低值区 ,TPSA和F/T值在两组间差别均无显著性意义 (P >0 .5 )。　结论　血清TPSA为前列腺癌标记物 ,F/T值作为TPSA的辅助指标 ,在诊断灰区有重要价值     

Kidney Transplantation in Patients with Antibodies against Donor HLA Class II

The immunologic risk associated with donor-specific antibodies (DSA) against Class II human leukocyte antigens (HLA) in kidney transplant (KTx) recipients is unclear. The aim of this study was to determine the outcome of KTx when DSA was detected only against HLA Class II. To isolate the impact of anti-Class II DSA, we retrospectively analyzed 12 KTx recipients who at baseline had a positive B-cell flow cytometric crossmatch (FXM) and a negative T-cell FXM. Using alloantibody specification analysis, 58.3% (7/12) had DSA against donor Class II and 41.7% had no demonstrable DSA. Biopsy-proven AMR occurred in 57% (4/7) in the Class II(+) group and 0% in the Class II(-) group (p > 0.05). Peritubular capillaries stained positive for C4d in 86% (6/7) of the Class II(+) patients and in 40% (2/5) of the Class II(-) patients (p > 0.05). One patient in the Class II(+) group lost their graft at 3 months to accelerated transplant glomerulopathy, while all other grafts were functioning 3-37 months posttransplant despite the persistence of anti-Class II DSA. We conclude that KTx recipients with clearly defined anti-Class II DSA are at risk for humoral rejection suggesting that desensitization and/or close posttransplant monitoring may be needed to prevent AMR.     

Propensity score to evaluate prognosis in pregnancy-associated breast cancer: Analysis from a French cancer network

PurposeTo compare the prognosis of pregnancy associated breast cancer occurring during pregnancy (BCP) to non-pregnancy associated breast cancers (non-BCP) in young women managed at a national expert center.MethodsRetrospective cohort study of a prospective database using propensity score matching (PSM) analysis with known prognostic factors.ResultsWe analyzed data of 49 patients with BCP and 104 with non-BCP diagnosed between 2002 and 2017 at Tenon University Hospital (Paris, France). The BCP tumors were often locally advanced (lymph node metastases in 59%), of high grade (55%) and highly proliferative (67% with Ki67 ≥ 20%). After PSM, breast cancer-free survival (p = 0.45) and breast cancer specific survival (p = 0.81) were similar in the two groups. The recurrence rate was 12% vs 18% (p = 0.45) and the death rate was 6% vs 8% (p = 0.74) for the BCP and non-BCP groups, respectively. No difference in recurrence type was observed between the groups (p = 0.60).ConclusionsAfter PSM for known prognostic factors, the prognosis of BCP patients did not differ from that of young patients with non-BCP.     

附睾蛋白酶抑制剂对前列腺特异性抗原活性的抑制作用

目的 观察附睾蛋白酶抑制剂(Eppin)是否抑制前列腺特异性抗原(PSA)酶活性.方法 利用分子克隆技术体外构建、表达、纯化重组Eppin和PSA.利用PSA水解变色底物S-2586的颜色变化,于分光光度计下测定其吸光度值,代表PSA酶反应速度,反应体系是在缓冲液0.1 mol/LTris-HCl,pH8.3,1.0 mol/L NaCl中进行,观察不同浓度Eppin的加入对PSA酶反应速度的影响.结果通过体外重组技术获得较高纯度和生理活性的Eppin和PSA,通过PSA水解变色底物S-2586的检测,重组PSA具有酶活性,0.3 μmol/L PSA与底物S-2586反应的饱和曲线分析显示Km(反应速度为最大反应速度一半时的底物浓度)值是0.5 μmol,底物饱和浓度0.2 mmol/L,分别加入4中不同浓度的重组Eppin 0、0.56、1.16、2.32 μmol/L,随着Eppin浓度的增加,PSA水解其变色底物S-2586速度明显减慢,PSA活性越来越受到抑制.结论 附睾蛋白酶抑制剂(Eppin)是前列腺特异性抗原(PSA)一种新的特异性抑制剂.

Abstract：

Objective To investigate the inhibitory effects of the epididymal protease inhibitor (Eppin) on the activity of prostate specific antigen (PSA).Methods Recombinant Eppin and recombinant PSA were produced by molecular cloning technique in vitro.The enzymatical analysis of Eppin inhibiting PSA was done in the reaction buffer 0.1 mol/L Tris-HC1,pH 8.3,1.0 mol/L NaCl.The hydrolysis of velocity of PSA to the chromogenic substrate S-2586 was detected by spectrometer.Results Recombinant Eppin and PSA with high purity were produced by molecular cloning technique.The recombinant PSA had the enzymatical activity by hydrolyzing its substrate S-2586.0.3μmol/L PSA and the substate S-2586 reaction to the saturation curve analysis showed that Km( response rate of half the maximum reaction rate when the substrate concentration) value was 0.5μmol,and substrate saturated concentration was 0.2 mmol/L.With the increases of Eppin (0,0.56,1.16,2.32μmol/L),the hydrolysis velocity of PSA to S-2586 was slowed down.Conclusion Eppin,as a new inhibitor,specifically inhibits the activity of PSA.     

The limits of passive motion are variable between and unrelated within normal tibiofemoral joints

Patient‐to‐patient differences should be accounted for in both clinical evaluations and computational models of knee laxity. Accordingly, the objectives were to determine how variable the laxities are between knees by determining the range of the internal–external (I‐E), varus–valgus (V‐V), anterior–posterior (A‐P), and compression–distraction (C‐D) limits of passive motion, and how related the laxities are within a knee by determining whether these limits are correlated with one another. The limits in I‐E (± 3 Nm), V‐V (± 5 Nm), A‐P (± 45 N), and C‐D (± 100 N) were measured in 10 normal human cadaveric knees at 0° to 120° flexion in 15° increments using a six degree‐of‐freedom load application system. The ranges from 15° to 120° flexion of the I‐E limits were greater than 3.6°, of the A‐P limits were greater than 1.8 mm, and of the varus limits were greater than 1.4°. The ranges from 30° to 120° flexion of the distraction limits were greater than 2.0 mm. Twenty‐four of the 28 pair‐wise comparisons between the limits had a correlation coefficient less than 0.65. These results demonstrate that a patient‐specific approach, including all degrees of freedom of interest, is necessary during clinical evaluations of laxity and when creating and validating computational models of the tibiofemoral joint. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1594–1602, 2015.     

Pathogen Stimulation History Impacts Donor‐Specific CD8+ T Cell Susceptibility to Costimulation/Integrin Blockade–Based Therapy

Recent studies have shown that the quantity of donor‐reactive memory T cells is an important factor in determining the relative heterologous immunity barrier posed during transplantation. Here, we hypothesized that the quality of T cell memory also potently influences the response to costimulation blockade‐based immunosuppression. Using a murine skin graft model of CD8⁺ memory T cell–mediated costimulation blockade resistance, we elicited donor‐reactive memory T cells using three distinct types of pathogen infections. Strikingly, we observed differential efficacy of a costimulation and integrin blockade regimen based on the type of pathogen used to elicit the donor‐reactive memory T cell response. Intriguingly, the most immunosuppression‐sensitive memory T cell populations were composed primarily of central memory cells that possessed greater recall potential, exhibited a less differentiated phenotype, and contained more multi‐cytokine producers. These data, therefore, demonstrate that the memory T cell barrier is dependent on the specific type of pathogen infection via which the donor‐reactive memory T cells are elicited, and suggest that the immune stimulation history of a given transplant patient may profoundly influence the relative barrier posed by heterologous immunity during transplantation.