Effects of acute liver injury on blood coagulation

Summary.  The mechanisms leading to the hemostatic changes of acute liver injury are poorly understood. To study these further we have assessed coagulation and immune changes in patients with acute paracetamol overdose and compared the results to patients with chronic cirrhosis and normal healthy controls. The results demonstrate that in paracetamol overdose coagulation factors (F)II, V, VII and X were reduced to a similar degree and were significantly lower than FIX and FXI (mean levels 0.28, 0.16, 0.13, 0.19, 0.51 and 0.72 IU mL⁻¹, respectively). In cirrhosis, by contrast, FII, FV, FVII, FIX and FX were equally reduced whilst FXI was lower than the other factors (mean levels 0.64, 0.69, 0.62, 0.60, 0.66 and 0.40 IU mL⁻¹, respectively). FVIII was raised in paracetamol overdose patients but normal in those with cirrhosis (mean levels 1.95 and 1.01 IU mL⁻¹, respectively). Interleukin-6 and tumor necrosis factor-α levels were raised in both patient groups, but higher levels were found in paracetamol overdose, compared to cirrhosis. Thrombin-antithrombin and soluble tissue factor levels were higher in those with acute liver injury but normal in cirrhosis. Antithrombin levels were reduced in both acute liver injury and cirrhosis. From these data we put forward a novel mechanism for the coagulation changes in acute paracetamol induced liver injury. We propose that immune activation leads to tissue factor-initiated consumption of FII, FV, FVII and FX, but that levels of FIX and FXI are better preserved because antithrombin inhibits the thrombin induced positive feedback loop that activates these latter factors.     

机械通气治疗小儿急性肺损伤

目的：探讨小儿急性肺损伤(ALI)的临床治疗。方法：对本院综合ICU1998年4月至2002年4月发生的22例小儿ALI的临床治疗情况进行回顾性分析。结果：本组22例小儿ALI采用呼吸末正压机械通气(PEEP)联合大剂量甲基强的松龙冲击治疗，有效率为86．36％；3例死亡，死亡率为13．64％，死于多器官功能不全综合征(MODS)。结论：机械通气治疗小儿ALI应选择最佳PEEP，动态监测动脉血气指标和X线胸片，在综合治疗基础上加用大剂量甲基强的松龙冲击治疗能收到较好的疗效。     

移植肝缺血-再灌注损伤程度的评估及其与肝移植患者预后的关系

目的探讨移植肝缺血-再灌注损伤程度的评估方法及其与肝移植患者预后的关系。方法218例良性终末期肝病患者，在移植肝恢复血液灌注后1h采取外周静脉血，测定丙氨酸转氨酶浓度（定义为基础肝功能），同时采用组织气体分析仪测定肝组织的氧分压，并取肝组织活检，计算水变性及坏死细胞百分比，分别对上述3项指标进行评分，再根据各指标得分之和将缺血-再灌注损伤程度划分为5级（0～Ⅳ级），统计围手术期（术后2周内）、术后近期（术后2周至1个月）、术后中远期（1个月以上）的患者死亡率。结果移植肝缺血再灌注损伤程度评为0级者157例（A组），死亡7例（4．5％），71．4％（5／7）死于术后3-6个月；缺血-再灌注损伤程度评为Ⅰ级者25例（B组），死亡5例（20．0％），80．0％（4／5）死于术后2周至3个月；缺血-再灌注损伤程度评为Ⅱ级者23例（C组），死亡5例（21．7％），80．0％（4／5）死于术后2周至3个月；缺血-再灌注损伤程度评为Ⅲ级者8例（D组），死亡7例（87．5％），85．7％（6／7）死于术后1个月内；缺血-再灌注损伤程度评为Ⅳ级者5例（E组），全部死亡，80．0％（4／5）死于术后1个月内。A组各期死亡率明显低于B组、C组（P〈0．05）和D组、E组（P〈0．01）；B组、C组间各期死亡率的差异无统计学意义（P〉0．05）；B组、C组各期死亡率均低于D组、E组（P〈0．05）。结论基础肝功能、组织氧分压以及水变性和坏死细胞百分比三项指标可基本反映移植肝缺血-再灌注损伤程度；缺血-再灌注损伤评级达Ⅲ～Ⅳ级者术后死亡率较高。     

亚低温治疗重型颅脑损伤中脑组织氧分压的临床意义

目的观察亚低温治疗重型颅脑损伤过程中患者颅内压及脑组织氧分压的变化及临床意义。方法将80例急性重型颅脑损伤患者,随机分为亚低温治疗组(40例)和对照组(40例)。亚低温组入院后或术后立即给予亚低温治疗,保持肛温在32~34℃,持续24h~5d;对照组给予常规治疗。两组均观察颅内压(ICP)和脑组织氧分压(PbtO2)变化。结果亚低温组治疗后,ICP明显下降,PbtO2逐渐升高,与对照组相比有显著性差异。结论亚低温治疗能降低脑外伤后增高的ICP,提高PbtO2;伤后24h内持续PbtO2<5mmHg预示患者预后不良。     

经鼻给予抗ICAM-1抗体对大鼠脑缺血再灌注损伤的保护作用

目的 探讨经鼻腔给予抗细胞间黏附分子-1(ICAM-1)单克隆抗体(单抗)对大鼠脑缺血再灌注损伤的保护作用.方法 将30只雄性Wistar大鼠随机分为假手术组、脑缺血再灌注组及脑缺血再灌注+经鼻给予高、中、低剂量抗ICAM-1单抗干预组.采用插线法制作局灶脑缺血再灌注模型.各干预组于缺血1 h经鼻给予抗ICAM-1单抗,再灌24 h后取脑行冠状切片.采用TTC、HE及免疫组化染色法测定脑梗死体积及免疫组化阳性区占总面积比.结果 缺血再灌注组脑标本均可见缺血侧的脑膜充血,脑组织肿胀;单纯脑缺血再灌注组及低、中、高抗ICAM-1单抗干预组脑梗死体积(以像素值表示)分别为57 042±12 483、32 871±4 325、25 932±3 103和15 325±3 356,免疫组化阳性区面积占总面积比分别为(6.64±0.476)%、(5.15±0.987)%、(4.36±0.682)%和(3.42±0.537)%,各组间差异均有统计学意义.结论 (1)脑缺血再灌注可使脑组织ICAM-1表达显著增高;(2)经鼻腔给予抗ICAM-1单抗可有效降低脑组织ICAM-1的表达,缩小脑梗死体积;(3)经鼻腔给予抗ICAM-1单抗的剂量同脑梗死体积呈负相关;(4)脑缺血再灌注时ICAM-1免疫组化阳性区面积比与脑梗死体积呈正相关.     

脊髓损伤大鼠的阴茎海绵体肌电图研究

目的探讨海绵体肌电图诊断脊髓性勃起功能障碍的价值。方法将24只成年雄性SD大鼠(300～400 g)分成:对照组、T9和L6损伤组(每组8只)。损伤脊髓1周后,用肌电图仪采集注射阿朴吗啡前后阴茎肌电数据,采集频率20～3 000 Hz、扫描速度5 ms／d、灵敏度10 μV／d。用t检验方法分析统计数据。结果对照组使用阿朴吗啡10 min均方根振幅为(5．60±0．89)μV, 大于T9损伤组(3．60±1．14)μV(P<0．05);使用阿朴吗啡前、使用后5 min和10 min高／低功率比均为0．05±0．03,小于L6损伤组0．13±0．04、0．15±0．07、0．13±0．07(P<0．05)。T9损伤组使用阿朴吗啡后5 min和10 min平均频率分别为(122．40±47．99)、(151．80±76．42)Hz,较L6损伤组(278．83±118．66)、(265．00±81．35)Hz低(P<0．05)。结论海绵体肌电图对脊髓性勃起功能障碍有诊断价值。     

寰椎Jefferson骨折伴横韧带损伤的诊治

目的 分析总结寰椎Jefferson骨折伴横韧带损伤的诊断和治疗。方法 1995年3月-2005年3月收治26例寰椎Jefferson骨折伴横韧带损伤患者。其中新鲜骨折20例，陈旧性骨折6例。所有患者均伴有不同程度的横韧带损伤，23例有神经损害表现。X线检查显示寰椎弓环及侧块不同部位骨折，寰齿间距（ADI）为4．7mm。5例行非手术治疗，其余21例行颈椎后路枕颈融合术或寰枢椎融合术治疗。结果所有患者术后获6～24个月（平均15个月）随访，21例手术治疗患者术后临床症状缓解；5例非手术治疗患者中，4例成功，另1例失败再行颈后路寰枢椎融合术治疗，术后疗效满意。结论 寰椎Jefferson骨折伴横韧带损伤患者的临床表现主要取决于韧带断裂后寰椎前脱位的程度以及是否造成脊髓压迫，诊断以ADI为主、并结合外伤史及临床表现。对于可能存在寰枢椎不稳或已有横韧带损伤且存在典型神经症状的患者，应早期行寰枢椎融合术或枕颈融合术治疗。     

Ex Vivo Application of Carbon Monoxide in University of Wisconsin Solution to Prevent Intestinal Cold Ischemia/Reperfusion Injury

Carbon monoxide (CO), a byproduct of heme catalysis, was shown to have potent cytoprotective and anti-inflammatory effects. In vivo recipient CO inhalation at low concentrations prevented ischemia/reperfusion (I/R) injury associated with small intestinal transplantation (SITx). This study examined whether ex vivo delivery of CO in University of Wisconsin (UW) solution could ameliorate intestinal I/R injury. Orthotopic syngenic SITx was performed in Lewis rats after 6 h cold preservation in control UW or UW that was bubbled with CO gas (0.1-5%) (CO-UW). Recipient survival with intestinal grafts preserved in 5%, but not 0.1%, CO-UW improved to 86.7% (13/15) from 53% (9/17) with control UW. At 3 h after SITx, grafts stored in 5% CO-UW showed improved intestinal barrier function, less mucosal denudation and reduced inflammatory mediator upregulation compared to those in control UW. Preservation in CO-UW associated with reduced vascular resistance (end preservation), increased graft cyclic guanosine monophosphate levels (1 h), and improved graft blood flow (1 h). Protective effects of CO-UW were reversed by ODQ, an inhibitor of soluble guanylyl cyclase. In vitro culture experiment also showed better preservation of vascular endothelial cells with CO-UW. The study suggests that ex vivo CO delivery into UW solution would be a simple and innovative therapeutic strategy to prevent transplant-induced I/R injury.