膀胱出口部分梗阻大鼠逼尿肌胆碱能和肾上腺素能受体变化的研究

目的观察大鼠膀胱出口部分梗阻后不同时间逼尿肌胆碱能（M）、肾上腺素能β及α1受体的变化。方法40只大鼠分为对照组、假手术组、梗阻2周组和梗阻5周组,每组10只。放射配基法测定逼尿肌M、β及α1受体密度和平衡解离常数。离体逼尿肌条拉力实验观察梗阻2周和5周后逼尿肌对氯化氨甲酰胆碱和异丙肾上腺素产生的收缩和舒张反应。结果4组M受体密度分别为（121．87±15．32）、（122．34±26．56）、（138．66±24．16）和（131．54±23．09）fmol／mg,β受体密度分别为（83．18±7．51）、（82．20±6．24）、（92．21±6．53）和（86．32±5．02）fmol／mg。梗阻组M受体和β受体密度与对照组及假手术组相比,差异有统计学意义（P〈0．05）,梗阻5周组较2周组降低（P〈 0．05）。4组α1受体密度分别为（30．08±3．51）、（31．07±2．99）、（29．56±3．21）和（28．31±1．16） fmol／mg,梗阻组与对照组及假手术组相比,差异无统计学意义（P〉0．05）。对照组M、β、α1受体平衡解离常数分别为（2．18±0．13）、（5．63±0．44）、（4．68±0．34）mmol／L,假手术组分别为（2．54±0．96）、（5．74±0．41）、（4．79±0．42）mmol／L,梗阻2周组分别为（2．22±0．36）、（5．66±0．32）、（4．56±0．33）mmol／L,梗阻5周组分别为（2．32±0．25）、（5．56±0．19）、（4．55±0．18）mmol／L,组间比较差异无统计学意义（P〉0．05）。氯化氨甲酰胆碱和异丙肾上腺素引起逼尿肌条的收缩和舒张均呈浓度依赖性反应（P〈0．05）。结论大鼠膀胱出口部分梗阻后可能引起逼尿肌M、β及α1受体的改变,导致膀胱功能变化。     

胆固醇结石患者肝脏核受体基因表达的研究

目的研究胆囊胆固醇结石患者肝脏的核受体基因：肝脏X受体α（liver Xreceptor α，LXRα、法尼醇受体（farnesoid X receptor，FXR）、人类固醇异生物受体（steroid xenobiotic receptor，SXR）及肝受体同类物1（liver receptor homolog 1，LRH-1）的表达，探讨胆固醇结石病的发病机理。方法27例胆囊胆固醇结石患者（胆石组），男6例，女21例，平均年龄（52．44±1．92）岁。10例无胆石症的胆囊息肉患者为对照（对照组），男6例，女4例，平均年龄（47．10±2．73）岁。测定胆石胆固醇成分及血清脂类成分：总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-ch）、载脂蛋白（Apo）B和ApoA1和胆汁脂类成分（胆固醇、磷脂和胆汁酸），并计算胆汁总脂和胆汁胆固醇饱和指数。实时定量PCR法测定肝脏LRH-1、FXR、SXR及LXRα基因的表达量。结果胆石组血清中HDL—ch浓度明显低于对照组[（0．93±0．05）mmol／L vs（1．33±0．09）mmol／LD，P〈0．001；ApoA1浓度也低于对照组[（1．19±0．05）g／L vs（1．36±0．06）g／L]，P〈0．05；血清ApoB、TC和TG2组比较差异均无统计学意义（P〉0．05）。胆石组胆汁呈胆固醇过饱和（胆固醇过饱和指数：1．17±0．02 vs 0．79±0．10，P〈0．001）；胆汁胆固醇摩尔百分比浓度较对照组升高[（7．96±0．39）mol％vs （5．26±0．89）mol％]，P〈0．01；胆汁总脂较对照组明显下降[（104．72±10．51）g／L vs （154．24±14．20）g／L]，P〈0．05；胆汁中胆汁酸和磷脂成分2组比较差异均无统计学意义（P〉0．05）。胆石组LRH-1表达高于对照组（14．18±1．80 vs 7．22±2．22），P〈0．05，LXRα、FXR和SXR表达2组差异无统计学意义（P〉0．05）。结论人类肝脏LRH-1的表达增高与胆囊胆固醇结石形成有关。     

自体骨髓细胞经门静脉移植治疗肝硬化与肝功能不全的临床研究

目的观察自体骨髓细胞经门静脉移植对肝硬化和肝功能不全的治疗效果。方法2005年2月至2006年6月在我科接受手术治疗的40例肝硬化门静脉高压症患者（脾切除、断流术或内镜食道曲张静脉套扎术）,被随机分为治疗组和对照组,每组20例。两组患者于术中埋置“门静脉导管-皮下药盒”,术后3-4周,治疗组经移植通道输注自体骨髓细胞,而对照组只输注生理盐水。在第1次输注后每隔1个月再重复进行输注,共输注3次。第3次输注后1个月进行疗效评价。结果（1）两组恢复均顺利,未发现与移植操作有关的不良反应或并发症。（2）丙氨酸转氨酶、总胆红素、白蛋白和凝血酶原时间：治疗组分别由（60±52）μmol／L、（26±15）μmol／L、（33±5）μmol／L和（18±2）s变为（26±15）μmol／L、（14±8）μmol／L、（41±3）μmol／L和（12±2）s（P〈0．01）;对照组分别由（47±37）μmol／L、（22±23）μmol／L、（35±4）μmol／L和（18±4）s变为（65±51）μmol／L、（19±42）μmol／L、（35±4）μmol／L和（18±4）s（P〉0．05）;治疗组优于对照组（P〈0．01）。（3）血清透明质酸和前胶原Ⅲ肽：治疗组分别由（188±160）ng／ml和（13±18）ng／ml变为（104±80）ng／ml和（8±9） ng／ml（P〈0．05）;对照组分别由（79±193）ng／ml和（10±16）ng／ml变为（136±187）ng／ml和（9±17）ng／ml（P〉0．05）;治疗组亦优于对照组（P〈0．01）。结论自体骨髓细胞经门静脉移植可改善肝功能和肝纤维化血清学指标。     

贲门癌患者血浆纤维蛋白原含量及其临床意义

目的观察贲门癌患者血浆Fibrinogen（FIB）水平与肿瘤临床分期、浸润程度和转移的关系，探讨其对于贲门癌患者的辅助诊断及判断预后的临床意义。方法结合临床资料，回顾分析使用美国贝克曼库尔特ACL8000型全自动凝血系列分析仪检测的我科收治的780例贲门癌患者的血浆中FIB含量。结果I～Ⅳ期FIB（g／L）含量分别为（3．13±0．73）、（4．08±0．71）、（4．87±0．83）、（5．59±0．74）。T1～T4FIB（g／L）含量分别为（3．16±0．69）、（3．59±0．74）、（4．52±0．75）、（5．47±0．68）。NOMFIB（g／L）含量分别为（3．21±0．60）、（4．17±0．43）、（5．06±0．72）、（5．59±0．74）差异均有统计学意义（P〈0．05）。结论贲门癌患者存在FIB异常，且与临床分期成正相关。     

奥美拉唑对大鼠减体积肝移植后肝再生的影响

目的观察奥美拉唑对大鼠减体积肝移植肝细胞再生的影响。方法建立大鼠减体积肝移植模型，实验组移植后即时给予奥美拉唑，对照组予生理盐水。两组分别于肝移植术后分为5组（n=8），观察术后3、5、7、10、14d血清丙氨酸转氨酶、天冬氨酸转氨酶值、移植肝重／供肝减体积前全肝重比值、移植肝细胞有丝分裂指数（MI）、增殖细胞核抗原（PCNA）表达指数、溴脱氧尿嘧啶核苷（BrdU）掺入指数及血清胃泌素值。结果大鼠减体积肝移植术后5d肝细胞再生达高峰，实验组的再生活性显著高于对照组，MI为（2．54±0．24）％和（1．71±0．16）％（P〈0．01）、PC—NA指数为（26．96±2．09）％和（18．73±1．94）％（P〈0．01）、BrdU指数为（10．24±1．11）％和（5．75±0．88）％（P〈0．01）。术后7d，实验组和对照组移植肝重／全肝重比值分别为（76．3±1．6）％和（71．2±1．0）％（P〈0．05），血清胃泌素水平分别为（441．9±25．9）ng／L和（292．9±14．2）ng／L（P〈0．05）。术后14d，实验组和对照组移植肝重／全肝重比值分别为（94．5±1．7）％和（86．9±1．5）％（P〈0．01），血清胃泌素水平分别为（487．8±29．4）ng／L和（291．7±21．6）ng／L（P〈0．01）。实验组和对照组血清ALT、AST值差异无统计学意义。结论奥美拉唑能促进减体积肝移植术后的肝细胞再生，其作用可能与胃泌素分泌增高有关。     

α1D与α1A受体亚型对大鼠不稳定逼尿肌收缩功能的影响

目的研究α1D及α1A受体亚型对大鼠膀胱出口梗阻（BOO）引起的不稳定逼尿肌（D1）收缩性、自律性的影响。方法建立Wistar大鼠BOO模型，充盈性膀胱测压确定D1模型，通过离体肌条牵拉实验，记录高选择性α1D及α1A受体亚型拮抗剂作用下，D1组和假手术对照组肌条自发性收缩频率及收缩力变化。结果35只BOO模型大鼠存活32只，D1发生率为71．9％。在一定张力前负荷下离体逼尿肌均产生自发性收缩，D1组肌条自发性收缩频率及收缩力均明显高于对照组；α1受体激动剂苯福林（PE）可使肌条自发性收缩频率及收缩力增加，选择性α1A受体拮抗剂5-MU能降低[（2．43±0．71）次／min，（0．14±0．03）g]对照组肌条的自发性收缩频率（2．64±0．72）次／min及收缩力（O．20±0．04）g，也能拮抗[（2．37±0．57）次／min，（0．19±0．02）g]PE所致的对照组肌条收缩频率（4．22±0．37）次／min和收缩力（0．31±0．03）g的增加（P〈O．01），而对D1逼尿肌作用不明显。选择性α1D受体拮抗剂BMY7378能降低[（2．32±0．56）次／min，（0．18±0．04）g]DI组肌条的自发性收缩频率（5．06±1．02）次／min及收缩力（0．42±0．08）g，并拮抗[（4．28±0．71）次／min，（0.48±0．04）g]PE所致的肌条收缩频率（6．73±0．61）次／min和收缩力（0.95±0．07）g的增加，但对正常逼尿肌作用不明显。结论 α1受体兴奋可使逼尿肌收缩频率及收缩力增加，正常逼尿肌中α1受体主要通过α1A亚型发挥作用，而梗阻性不稳定逼尿肌则主要通过α1D亚型发挥作用。     

紧密连接蛋白ZO-1在兔脊髓空洞前状态中的表达

目的 观察紧密连接蛋白ZO-1在实验性兔脊髓空洞前状态中的表达及变化规律。方法 通过Kaolin枕大池注射，建立兔脊髓空洞模型，分别在术后第1、3、7、14、21天，应用Evansblue法、免疫组织化学和Western blot测定印只（实验组40只，对照组20只）中国白兔血脊髓屏障功能、上颈髓中ZO-1表达含量，并探讨其内在相关性。结果 与对照组比较，实验组动物脊髓组织中Evansblue含量在术后第3天开始增高（2．79±0．42）mg／L，7d达到高峰（3．53±0．45）mg／L，持续到14d（3．45±0．35）mg／L，21d好转（3．36±0．27）mg／L。Western blot结果显示，ZO-1表达含量在第3天开始减弱（195．32±23．50），第7天（126．28±27．40）、14d（119．36±18．70）表达最弱，21d（165．70±21．20）部分恢复。同时免疫组织化学测定ZO-1表达变化趋势和Western blot结果一致。统计学分析表明，ZO-1表达与Evansblue含量在空洞前状态中的时相变化具有明显相关性（r=-0．9502，P〈0．01）。结论 ZO-1的表达强度变化趋势与实验性兔脊髓空洞前状态中的血脊髓屏障功能破坏程度变化相一致，ZO-1表达下降是形成实验性脊髓空洞前状态病理改变的重要因素。     

依那普利拉对严重烫伤大鼠早期心肌损害的防治作用

目的了解依那普利拉对烧伤后早期心肌损害的防治效果。方法将60只SD大鼠制成30％TBSAⅢ度烫伤模型，分为单纯烫伤组（30只，伤后常规补液）和依那普利拉组（30只，伤后立即一次性腹腔注射依那普利拉1mg／kg并行常规补液）。另取6只大鼠不致伤作为正常对照组。检测正常对照组及2组烫伤大鼠伤后1、3、6、12、24h血清心肌肌钙蛋白I（cTnI）的含量、心肌型肌酸激酶同工酶（CK—MB）的活性，并观察心肌组织病理学变化。结果（1）单纯烫伤组大鼠伤后各时相点cTnI、CK—MB均显著高于正常对照组（P〈0．01）。依那普利拉组伤后各时相点cTnI为（1．32±0．12）-（2．47±0．22）μg／L，均显著低于单纯烫伤组[（6．42±0．96）-（15．10±3．69）μg／L，P〈0．01]；其各时相点CK—MB活性为（438±68）-（5569±322）U／L，亦均低于单纯烫伤组[（2556±74）-（8047±574）U／L，P〈0．05或P〈0．01]。（2）与正常对照组比较，单纯烫伤组伤后出现心肌细胞浊肿、间质血管扩张充血、炎性细胞浸润等病理改变；依那普利拉组病变程度较之减轻。结论大鼠严重烫伤后早期心肌组织受损明显，依那普利拉能显著减轻这些损害。     

雄激素对前列腺癌细胞PAR基因表达的影响及其机制

目的观察在前列腺癌特异性高表达的癌基因前列腺雄激素调节基因（PAR）对雄激素的反应及其机制，探讨通过抑制PAR基因治疗雄激素非依赖性前列腺癌的可能性。方法用细胞计数检测双氢睾酮对LNCaP、PC3细胞增殖的刺激效应，以逆转录-聚合酶链反应（RT-PCR）分别检测双氢睾酮对LNCaP、PC3细胞PAR基因mRNA表达水平的影响及双氢睾酮和其拮抗剂联合作用对LNCaP细胞PAR基因mRNA表达水平的影响。结果低浓度（0．001～1nmol／L）双氢睾酮刺激可促进LNCaP细胞增殖，且刺激效应随双氢睾酮浓度升高而增强，在0．1nmol／L浓度时达最大，细胞计数为（27、54±0．71）×10。爪／孔，为对照组（16．13±1．03）×10。爪／孔的（170．74±0．78）％；同时使PAR基因mRNA表达水平上调在0．1nmol／L浓度时最高，为对照组的（272．42±8．24）％，P〈0．05）；高浓度（10、100nmol／L）双氢睾酮则抑制其增殖和PAR基因表达，在10nmol／L和100nmol／L浓度，细胞计数分别为（12．02±0．41）×10。／孔、（11．13±1．92）×10^4／孔（P〈0．05）；PAR基因mRNA表达水平分别为对照组的（76．64±2．47）％和（52．97±1．07）％，（P〈0．05）。这一调节效应可以为氟他胺所阻断。双氢睾酮对PC3细胞生长及PAR基因mRNA表达无明显影响（P〉0．05）。结论PAR可能是雄激素．雄激素受体通路下游的前列腺癌特异性癌基因，有望成为雄激素非依赖性前列腺癌基因和药物治疗的潜在靶点。     

低温氧合血微流量持续灌注保存大鼠心脏的效果

目的探讨低温氧合血微流量持续灌注保存大鼠心脏的效果。方法切取Wistar大鼠心脏，随机分为3组，实验组的心脏以4℃氧合血微流量（1ml／h）持续灌注低温保存10h；对照组的心脏以4℃St．Thomas液微流量持续灌注低温保存10h；单纯冷保存组的心脏以4℃St．Thomas液单纯浸泡保存10h。保存后的鼠心用Langendorff装置灌注，生物机能实验系统测定血流动力学指标；高效液相色谱仪测定心肌细胞的ATP含量；光镜和电镜观察心肌组织和线粒体的形态学改变。结果在再灌注30min时，实验组的左心室收缩压（LVSP）为（38．25±3．84）mm Hg，左心室发展压（LVDP）为（32．54±4．01）mm Hg，左心室压力微分（±dp／dt）为（1080±123）mm Hg／s；对照组的LVSP为（34．48±4．68）mm Hg，LVDP为（19．27±4．63）mmHg，±dp／dt为（935±196）mmHg／s；单纯冷保存组的LVSP为（32．14±4．95）mmHg，LVDP为（16．99±4．85）mmHg，±dp／dt为（825±302）mmHg／s，实验组的上述血流动力学指标优于对照组和单纯冷保存组（P〈0．05）。实验组心肌细胞的ATP含量为（1．759±0．502）μmol／L，对照组的ATP为（1．453±0．573）μmol／L，单纯保存组的ATP为（1．059±0．463）μmol／L，实验组的ATP含量明显高于对照组和单纯冷保存组（P〈0．05）。实验组的心肌组织和细胞超微结构的变化轻于对照组和单纯冷保存组。结论低温氧合血微流量持续灌注能改善大鼠心脏的保存效果。     

Successful prevention of tunneled central catheter infection by antibiotic lock therapy using cefazolin and gentamicin

Catheter-related bacteremia (CRB) is one of the various complications related to hemodialysis (HD). As a result of this high rate of infection, the antibiotic lock technique (ALT) has been recommended to prevent CRB. However, adverse effects of ALT such as increased emergence of strains resistant to antibiotics and increased mechanical dysfunction catheter were poorly evaluated. We prospectively evaluated the efficacy of catheter-restricted filling using an antibiotic lock solution in preventing CRB. A total of 233 HD patients requiring 325 new tunneled catheters while waiting for placement and maturation of an arteriovenous fistula or graft were enrolled in this study. Patients with a tunneled catheter were assigned to receive either an antibiotic–heparin lock solution (antibiotic group: cefazolin 10 mg/ml, gentamicin 5 mg/ml, heparin 1,000 U/ml) or a heparin lock solution (no-antibiotic group: heparin 1,000 U/ml) as a catheter lock solution during the interdialytic period. The present study aimed to assess the efficacy of ALT using cefazolin and gentamicin in reducing CRB in patients undergoing HD with tunneled central catheter and to identify its adverse effects. CRB developed in 32.4 % of patients in the no-antibiotic group and in 13.1 % of patients in the antibiotic group. CRB rates per 1,000 catheter-days were 0.57 in the antibiotic group versus 1.74 in the no-antibiotic group (p < 0.0001). Kaplan–Meier analysis also showed that mean CRB-free catheter survival was significantly higher in the antibiotic group than in the no-antibiotic group (log-rank statistic 17.62, p < 0.0001). There was statistically significant difference between the two groups in causative organisms of CRB, with predominance of negative culture in both groups, but this prevalence was higher in ALT group (57.9 vs 90.1 %, p < 0.0001), and the two groups also were different in prevalence of gram-positive bacteria as causing organisms (ALT group 21.05 vs = 0 % in control group, p < 0.0001). There was no statistically significant difference between the two groups in drug-resistant germs. There were statistically significant differences between the two groups in the catheter removal causes, with higher rate of infectious cause in control group (12.32 vs 2.22 %, p < 0.0001) and mechanical cause in ALT group (28.26 vs 37.78 %, p < 0.0001). The results suggest that ALT may be a beneficial means of reducing the CRB rate in HD patients with tunneled catheter, without association between ALT and emergence of strains resistant. However, mechanical complications were more prevalent in antibiotic group. Further studies are required to determine the optimal drug regimen, concentrations for ALT, and its adverse effects.     

Prevention of uncuffed hemodialysis catheter-related bacteremia using an antibiotic lock technique: a prospective, randomized clinical trial

As a result of the high rate of infection, the NKF-K/DOQI guidelines recommended that an uncuffed catheter (UC) should not be used for longer than three weeks. However, the findings of the Dialysis Outcomes and Practice Patterns Study recognized that 48% of new hemodialysis patients in the US and 75% in Europe used UC for temporary access during arteriovenous fistula or graft maturation. The antibiotic lock technique (ALT) has been recommended to prevent catheter-related bacteremia (CRB). Here, we prospectively evaluated the efficacy of catheter-restricted filling using an antibiotic lock solution in preventing CRB. A total of 120 new hemodialysis patients requiring a temporary catheter while waiting for placement and maturation of an arteriovenous fistula or graft were enrolled in this study. Patients with a UC were randomly assigned to receive either an antibiotic-heparin lock solution (antibiotic group: cefazolin 10 mg/ml, gentamicin 5 mg/ml, heparin 1000 U/ml) or a heparin lock solution (no-antibiotic group: heparin 1000 U/ml) as a catheter lock solution during the interdialytic period. The end point of the trial was CRB. CRB developed in seven (11.7%) patients in the no-antibiotic group (Staphylococcus aureus, two; Staphylococcus epidermidis, five) whereas only one patient in the antibiotic group had S. aureus bacteremia. CRB rates per 1000 catheter-days were 0.44 in the antibiotic group versus 3.12 in the no-antibiotic group (P=0.031). Kaplan-Meier analysis also showed that mean CRB-free catheter survival of 59 days (95% CI, 58-61 days) in the antibiotic group was greater than that in the no-antibiotic group (55 days; 95% CI, 50-59 days). The results suggest that ALT may be a beneficial means of reducing the CRB rate in hemodialysis patients with UC.     

The incidence and costs of bacteremia due to lack of gentamicin lock solutions for dialysis catheters

The use of antibiotic lock solutions as prophylaxis for catheter‐associated blood stream infection (CRBSI) has been shown to be effective in previous randomized controlled trials. However, the cost‐effectiveness of this approach had not been studied. In 2012, the routine gentamicin‐heparin lock solution used in Auckland City Hospital was withdrawn from the market, leading to a change to heparin‐only lock. This was then replaced with gentamicin‐citrate lock in 2014. This situation allowed review of the CRBSI rate and financial impact of different catheter lock solutions. A retrospective audit was performed from 1 January 2011 to 31 December 2015 to investigate the rate of culture‐proven CRBSI in patients with tunneled cuffed dialysis catheters. There were 89 cases of CRBSI involving 64 patients in the 5‐year period. In comparison with the heparin‐only lock, both gentamicin‐heparin and gentamicin‐citrate locks had a significantly lower rate of bacteremia, with rate ratios of 0.46 (confidence interval 0.30‐0.72) and 0.11 (confidence interval 0.05‐0.22), respectively. The inpatient costs as a consequence of the CRBSI were NZ$27 792 per 1000 catheter days for heparin‐only lock, NZ$10 608.56 per 1000 catheter days for gentamicin‐heparin lock, and NZ$ 1898.45 per 1000 catheter days for gentamicin‐citrate lock. The lack of antibiotic lock solutions led to an increase in bacteremia rates and higher financial cost for inpatient management of bacteremia. Our findings highlight the importance of consistent supply of pharmaceuticals.     

Prevention of dialysis catheter-related sepsis with a citrate-taurolidine-containing lock solution.

BACKGROUND: The use of haemodialysis catheters is complicated by catheter-related sepsis. Intraluminal colonization of the catheter with bacteria is important in the pathogenesis of catheter-related sepsis. The use of a catheter lock solution containing the antimicrobial taurolidine might prevent bacterial colonization, thereby reducing the incidence of catheter-related sepsis. METHODS: In a randomized prospective trial, patients receiving a dialysis catheter were included and catheters were locked with either heparin or a citrate-taurolidine-containing solution. Blood cultures drawn from the catheter lumen were routinely taken every 2 weeks and at time of removal of the catheter to detect bacterial colonization. Catheter-related sepsis and exit-site infections were registered for both groups. RESULTS: A total of 76 catheters were inserted in 58 patients. The incidence of catheter colonization progressed slowly over time with no differences between dialysis catheters filled with heparin or citrate-taurolidine-containing solution. The number of exit-site infections was also similar between both groups. In the heparin group, four cases of catheter-related sepsis occurred as opposed to no sepsis episodes in the patients with catheters locked with the citrate-taurolidine-containing solution (P<0.5). No side effects with the use of citrate-taurolidine catheter lock solution were noted. CONCLUSIONS: This study shows that catheter filling with a solution containing the antimicrobial taurolidine may significantly reduce the incidence of catheter-related sepsis. Taurolidine appears to be effective and safe and does not carry the risk for side effects that have been reported for other antimicrobial lock solutions containing gentamicin or high concentrations of citrate.     

Antibiotic lock technique for prevention of cuffed tunnel catheter associated bacteremia

Background: Central venous cuffed tunnel catheters are commonly used for short term or long term hemodialysis access. However, catheter-associated bacteremia is a common complication. It has been suggested that the addition of antibiotics to the catheter during the interdialytic interval results in a decrease in bacterial colonization and thereby a decrease in catheter associated infections. To test this hypothesis, a prospective, randomized study was performed comparing a gentamicin citrate mixture to standard heparin as the catheter lock. The effect of covering the catheter hub in a sterile bag on the infection rate was additionally tested. Methods: From January 1999 to April 2000, all patients who underwent tunnel catheter placement or change (55 catheters) in the Nephrology Interventional Laboratory at Louisiana State University Health Sciences Center in Shreveport, were prospectively randomized as follows: group 1 (n=14): Antibiotic lock with tricitrasol (46.7%), gentamicin (40 mg/ml) and saline in a ratio of 1:5:5 and catheter hub covered with a sterile plastic bag after cleaning with a 10% povidone iodine solution; group 2 (n=22): Heparin lock and sterile plastic bag over catheter hub after cleaning with povidone iodine; and group 3 (n=19): Heparin lock alone. The primary end points of the study were catheter-associated bacteremia and thrombosis. Catheter loss due to access maturation, transplant or transfer were censored. Results: There were a total of 4,805 at risk patient-days. The total number of catheter associated bacteremias were one in group 1, four in group 2 and four in group 3. The number of catheter associated bacteremias per 1000 patient-days in each group was 0.62, 3.05, and 2.11 respectively. The sixty day percent survival of catheters in each group was 74 +/- 12, 55 +/- 12 and 59 +/- 11 respectively. Conclusions: 1) Tricitrasol and gentamicin as an antibiotic lock reduced the incidence of catheter associated bacteremia; 2) Covering the catheter hub with a sterile bag did not provide an additional advantage; 3) The antibiotic lock improved overall survival of catheters.     

Prevention of tunneled hemodialysis catheter-related infections using catheter-restricted filling with gentamicin and citrate: a randomized controlled study

Tunneled catheters are widely used for the provision of hemodialysis. Long-term catheter survival is limited by tunneled catheter-related infections (CRI). This study assesses the efficacy of catheter-restricted filling with gentamicin and citrate in preventing CRI in hemodialysis patients. A double-blind randomized study was conducted to compare heparin (5000 U/ml) with gentamicin/citrate (40 mg/ml and 3.13% citrate; ratio 2:1) as catheter-lock solutions. A total of 112 tunneled catheters in 83 patients were enrolled at the time of catheter insertion for commencement or maintenance of hemodialysis. The primary end point was CRI. Catheter malfunction, defined as blood flow rate of <200 ml/min for three consecutive dialyses and/or the use of urokinase, was also assessed as a secondary end point. Infection rates per 100 catheter-days were 0.03 in the gentamicin group versus 0.42 in the heparin group (P = 0.003). Kaplan-Meier survival analyses showed mean infection-free catheter survival of 282 d (95% CI, 272 to 293 d) in the gentamicin group versus 181 d (95% CI, 124 to 237 d) in the heparin group (log rank, 9.58; P = 0.002). Cox regression analyses showed a relative risk for infection-free catheter survival of 0.10 (95% CI, 0.01 to 0.92) in the gentamicin group when adjusted for gender, race, diabetes mellitus, catheter malfunction, and hemoglobin (P = 0.042). The incidence of catheter malfunction was not significantly different between groups. Predialysis gentamicin levels were significantly higher in patients randomized to gentamicin (gentamicin/citrate: median 2.8 mg/L [range, 0.6 to 3.5 mg/L], n = 5; heparin: median <0.2 mg/L [range <0.2 to 0.2 mg/L], n = 5; P = 0.008). Tunneled hemodialysis catheter-restricted filling with gentamicin and citrate is a highly effective strategy for prevention of CRI. Although citrate as a catheter-lock solution provides adequate anticoagulation for the interdialytic period, gentamicin levels suggest significant risk for chronic aminoglycoside exposure and associated ototoxicity. Before this technique is adopted, these preliminary observations warrant replication in future studies that will examine the efficacy and safety of lower doses of gentamicin or alternative agents with a reduced potential for toxicity.     

Citrate lock versus heparin lock for the prevention of catheter related infections in hemodialysis patients with tunneled catheters: a Meta-analysis of randomized controlled trials

ObjectiveTo study whether citrate lock is superior to heparin lock in the prevention of catheter related infections, bleeding complications and catheter malfunctions among hemodialysis patients with tunneled catheters. MethodsBy searching in Pubmed, the Cochrane Library, EMBASE, Ovid, WanFang, VIP, CNKI and CBM databases as well as related journals, qualified randomized controlled trials were included in a Meta - analysis using Revman 5.0 and STATA 10.0 software. The endpoints included catheter related infection, bleeding complication, thrombolytic treatment, catheter removal for malfunction, catheter thrombosis and all - cause death. ResultsFifteen randomized controlled trials were included with 1621 patients involved. Eight studies compared citrate alone with heparin lock, while 7 trials focused on citrate in combination with other antimicrobials. Pooled analysis demonstrated that incidence of catheter related infections in patients receiving citrate lock decreased by 47% compared with those on heparin (RR=0.53, 95%CI 0.36-0.77, P＜0.01). Subgroup analysis by types of citrate lock indicated that all combined lock solutions of citrate and other antimicrobials (citrate + gentamicin, citrate + taurolidine, citrate + methylene blue + methylparaben + propylparaben) were superior to heparin lock in preventing catheter-related infections (P＝0.01, 0.04, 0.01, respectively); citrate alone seemed to reduce catheter-related infection risk (RR＝0.68), but no statistically significant difference was observed (95%CI 0.38-1.21, P＝0.19). There were fewer patients with bleeding complications in citrate group (RR＝0.53, 95%CI 0.34-0.84, P＜0.01), while citrate showed no advantage over heparin lock in terms of thrombolytic treatment (P＝0.93), catheter removal for malfunction (P＝0.35), catheter thrombosis (P＝0.64) and all - cause death (P＝0.35). ConclusionsFor hemodialysis patients with tunneled catheters, combined lock solutions of citrate and other antimicrobials, rather than citrate alone, are superior to heparin in preventing catheter related infections. Citrate locks are associated with less bleeding complications, and are comparable to heparin in the maintenance of catheter patency.     

4％枸橼酸钠溶液在中心静脉置管血液透析患者中的应用

目的观察4％枸橼酸钠封管液在临时性中心静脉置管血液透析患者中的应用。方法将61例维持性血液透析患者随机分为2组,即4%枸橼酸钠封管组30例,肝素钠封管组31例。每次透析结束后,对2组患者分别以4％枸橼酸钠和肝素钠封管,均连续使用5周。评价2组患者导管相关的出血、感染和导管功能不良情况。结果①4％枸橼酸钠封管组导管相关的出血事件发生率较肝素钠封管组低,差异有统计学意义（P〈0．05）。②4％枸橼酸钠封管组有1例次出现透析中发热,但导管液和血液细菌培养均为阴性,肝素钠封管组有1例患者出现透析中发热,导管液培养为金黄色葡萄球菌阳性,血培养为阴性。③2组患者导管功能不良发生率无显著差异（P〉0．05）。结论对于临时性中心静脉置管的血液透析患者,4％枸橼酸钠封管液可作为常规肝素钠封管液的替代。     

Locking solutions for hemodialysis catheters; heparin and citrate--a position paper by ASDIN

There is wide variation in the use of solutions to "lock" or fill tunneled central venous catheters for dialysis. Some centers use undiluted heparin concentrations ranging from 1000 to 10,000 U/ml and other centers place from 1000 to 10,000 U per lumen. Based on available evidence, it appears that heparin 1000 U/ml, or 4% sodium citrate are suitable choices for lock solution to maintain patency of tunneled central venous catheters for dialysis. Risks from systemic anticoagulation are lower with heparin 1000 U/ml and 4% sodium citrate, compared with higher concentrations of heparin (5000 and 10,000 U/ml). The need for use of tissue plasminogen activator for maintaining catheter patency is increased by using heparin lock at 1000 U/ml, vs. higher concentrations. Higher concentrations of heparin lock should be reserved for patients who have evidence of catheter occlusion or thrombosis when heparin is used at 1000 U/ml. Similar choices for lock solution are sensible for acute hemodialysis catheters. When heparin is used for catheter lock, the injected volume should not exceed the internal volume of the catheter.     

血液透析双腔导管肝素封管液浓度的随机对照研究

目的 观察规律血液透析患者采用不同浓度肝素液进行颈内静脉留置双腔导管封管时对患者凝血功能、出血倾向、导管血栓形成等的影响,探讨合理的封管浓度。 方法 90例颈内静脉留置双腔导管作为维持性血液透析血管通路的患者根据不平衡指数最小分配原则随机分为3组（均n=30）,分别采用不同浓度肝素钠溶液进行封管。A组：纯肝素钠封管（6250 U/ml）;B组：中浓度肝素钠（1040 U/ml）+生理盐水溶液;C组：低浓度肝素钠（625 U/ml）+生理盐水溶液。测定封管后短期凝血功能,监测出血倾向、通路血栓形成情况、感染情况及血小板变化。 结果 A组在封管后30 min时凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、凝血酶时间（TT）等凝血功能指标均较基础值显著延长（P < 0.01）,在4 h后仍显著高于基础值（P < 0.05）,但24 h后PT、TT恢复至基础水平（P > 0.05）,APTT仍显著超过基础值（P < 0.05）。B组患者封管30 min后仅APTT显著超过基础值（P < 0.05）,且在4 h后恢复至基础水平（P > 0.05）。C组患者封管后PT、APTT和TT与基础值比较,差异均无统计学意义（P > 0.05）。观察期内,A组患者出血事件发生率显著高于B、C组（26.7% 比10%、0,P < 0.05）;C组血栓事件显著高于A、B组（23.3% 比0、10%,P < 0.05）。C组出现1例可疑导管相关感染。A组出现2例血小板中度减少。 结论 中等浓度肝素钠溶液进行颈内静脉留置双腔导管封管不良反应较少,可用于大多数患者。有高凝倾向的患者更适合采用高浓度肝素液;有出血倾向的患者可以用低浓度肝素钠溶液封管。