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急性脑损伤患者血清诱导神经元细胞凋亡:一种新的体外预后模型。

Apoptosis of neuronal cells induced by serum of patients with acute brain injury: a new in vitro prognostic model.

作者信息

Ballesteros Maria Angeles, López-Hoyos Marcos, Muñoz Pedro, Marin Maria Jose, Miñambres Eduardo

机构信息

Departamento de Medicina Intensiva, Hospital Universitario Marqués de Valdecilla, Avda Valdecilla s/n, 39008, Santander, Spain.

出版信息

Intensive Care Med. 2007 Jan;33(1):58-65. doi: 10.1007/s00134-006-0361-9. Epub 2006 Sep 9.

Abstract

OBJECTIVE

To investigate whether serum draining from the jugular bulb of patients with traumatic or haemorrhagic brain injury induced apoptosis of neuronal PC12 cells in vitro and whether the apoptotic rate correlated with patients' outcome at 6 months.

DESIGN AND SETTING

Prospective clinical investigation in a 21-bed intensive care unit (ICU) in a university hospital.

PATIENTS

Seventy patients who had suffered from acute brain injury requiring intensive care.

INTERVENTIONS

Jugular bulb vein and systemic samples were obtained on admission to the ICU and after 48 h. PC12 cells were incubated in the presence of 10% of heat-inactivated patient's sera and apoptotic rate was determined by flow cytometry using annexin V and 7-aminoactinomycin D.

RESULTS

Regional serum draining from the lesions induced higher early apoptosis of PC12 cells than systemic serum. Early apoptotic rate, Glasgow coma score, APACHE II score and the presence of pupil abnormalities were associated with mortality at 6 months in univariate statistical analyses. In logistic regression analysis only early apoptotic rate was an independent factor associated with mortality at 6 months (odds ratio: 1.502, 95% CI 1.2-1.9; p<0.001). The final model has a sensitivity of 82.4% and a specificity of 84.8% for predicting death within 6 months.

CONCLUSIONS

We developed a simple and reproducible in vitro model for predicting outcome in patients with traumatic or haemorrhagic brain injury that survived in the early phase. Our in vitro model combined with clinical and radiological measurements might improve the value of prognostic models to predict acute brain injury patients' outcome.

摘要

目的

探讨外伤性或出血性脑损伤患者颈静脉球引流血清是否能在体外诱导神经元PC12细胞凋亡,以及凋亡率是否与患者6个月时的预后相关。

设计与场所

在一所大学医院有21张床位的重症监护病房(ICU)进行的前瞻性临床研究。

患者

70例急性脑损伤需要重症监护的患者。

干预措施

在入住ICU时和48小时后采集颈静脉球静脉血和全身血样本。将PC12细胞在含有10%热灭活患者血清的条件下孵育,采用膜联蛋白V和7-氨基放线菌素D通过流式细胞术测定凋亡率。

结果

损伤部位引流的局部血清比全身血清诱导PC12细胞早期凋亡的程度更高。在单因素统计分析中,早期凋亡率、格拉斯哥昏迷评分、急性生理与慢性健康状况评分系统II(APACHE II)评分以及瞳孔异常与6个月时的死亡率相关。在逻辑回归分析中,只有早期凋亡率是与6个月时死亡率相关的独立因素(比值比:1.502,95%可信区间1.2 - 1.9;p<0.001)。最终模型预测6个月内死亡的敏感性为82.4%,特异性为84.8%。

结论

我们建立了一种简单且可重复的体外模型,用于预测早期存活的外伤性或出血性脑损伤患者的预后。我们的体外模型结合临床和影像学测量可能会提高预测急性脑损伤患者预后的模型价值。

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