来氟米特和环孢素A对异种心脏移植排斥反应中核因子κB信号传导的抑制作用

目的 探讨联合应用来氟米特(LeD和环孢素A(CsA)对大鼠异种心脏移植排斥反应中核因子kB(NF-kB)信号传导通路中核因子出抑制因子激酶α/β(IKKα/β)、NF-kB P65、核因子kB抑制因子α(IkBα)、细胞问粘附分子-1(ICAM-1)表达以及NF-kB DNA结合活性的影响.方法 以NIH小鼠为供者,Wismr大鼠为受者,施行颈部心脏移植,CsA组受者术后接受CsA腹腔注射,Lef组受者术后接受Lef灌胃,联合用药组受者术后接受CSA和Lef治疗,另设术后不接受任何药物处理的空白对照组.术后观察移植心脏存活时间,发生排斥反应时,切取移植心脏,进行组织病理学观察,采用免疫组织化学和Western印迹法检测各组移植心肌组织中IKKα/β、NF-kB P65、IkBa和ICAM-1的表达,凝胶电泳迁移率法检测NF-kBDNA结合活性.结果 空白对照组、CsA组、Lef组及联合用药组移植心脏的存活时间分别为(2.17±0.41)d、(2.50±1.05)d、(4.17±1.33)d和(6.50±2.56)d,联合用药组明显长于其它3组(P<0.05),Lef组明显长于空白对照组(P<0.05).4个组心肌组织中IKKα/β、NF-KB P65、IKBα和ICAM-1的表达由强到弱依次为空白对照组、CsA组、Lef组、联合用药组,其电泳条带积分吸光度值显示,Lef组的IKKα/β、NF-kB P65、IkBα和ICAM-1的表达明显低于空白对照组和CsA组(P<0.05),而联合用药组明显低于其它3组(P<0.05).Lef组的NF-kBDNA结合活性明显低于空白对照组及CsA组,联合用药组的NF-kDNA结合活性明显低于其它3组,差异均有统计学意义(P<0.05).结论 联合应用Lef和CsA可显著延长大鼠移植的异种(小鼠)心脏的存活时间,这可能与NF-kB信号通路中的IKKα/β、NFkB P65、IkBα、ICAM-1表达及NF-kB DNA结合活性受到抑制有关.     

环孢素A联合供者骨髓细胞输注延长大鼠移植心脏存活时间

目的：探讨环孢素A（CsA）联合供者骨髓细胞（DBMC）输注对同种大鼠移植心脏存活时间的影响。方法：制作Lewis大鼠到BN大鼠的异位（腹部）心脏移植模型，并按对受者处理的不同分为四组，对照组不进行特别处理，CsA组术后连续7d给予CsA5mg·kg^-1·d^-1，联合处理组分别于术中及术后第6天输注1×10^8个DBMC，术后连续7d给予CsA5nag·kg^-1·d^-1，DBMC组分别于术中及术后第6天输注1×10^8个DBMC；另设BN大鼠间的心脏移植作为对照（BN对照组）。观察移植心脏的存活时间，观测术后第6天血清白细胞介素2（IL-2）、移植心脏组织中肿瘤坏死因子（TNF-α）mRNA表达以及组织学改变，流式细胞仪检测术后第6、12、18天时受者外周血有核细胞中的供者来源细胞、CD3^＋ CD25^＋细胞、CD4^＋ CD25^＋细胞的百分比以及共刺激分子CD86表达、CD4^＋ CD45RC^＋／CD4^＋ CD45RC^-等。结果：联合处理组移植心脏存活时间为（21．6±3．2）d，明显长于对照组和DBMC组（P〈0．05），其血清IL广2为（313±95）pg／ml，心肌组织中TNF-α mRNA的表达量为0．12±0．10，均明显低于对照组和DBMC组（P〈0．05），排斥反应程度轻于其它3个移植组。联合处理组大鼠外周血有核细胞上CD86表达受到明显抑制；术后6、12d，联合处理组的CD4^＋ CD45RC^＋／CD4^＋ CD45RC^-比值低于对照组和DBMC组，CD3^＋ CD25^＋细胞百分比也低于对照组和DBMC组；接受DBMC输注者外周血中供者来源的有核细胞明显多于未接受DBMC者。结论：短疗程CsA联合DBMC输注能减轻大鼠心脏移植急性排斥反应程度，延长移植心脏存活时间。     

他克莫司联合青藤碱抑制大鼠心脏移植急性排斥反应

目的 探讨青藤碱（SIN）对大鼠心脏移植急性排斥反应抑制作用的机制，并评价青藤碱与他克莫司（FK506）联合作用的效果。方法 以PVG大鼠为供者，DA大鼠为受者，建立同种异体心脏移植模型。将受者随机分为4组，每组20只。对照组：采用生理盐水3ml·kg^-1·d^-1灌胃；SIN组：腹腔注射SIN 30mg·kg^-1·d^-1；FK506组：采用FK506 0．25mg·kg^-1·d^-1灌胃；联合组：腹腔注射SIN 30mg·kg^-1·d^-1并联合应用FK506 0．25mg·kg^-1·d^-1灌胃。各组均在术后24h内用药，用药时间共7d。观察各组移植心存活时间，术后第7d取部分受者的移植心做病理检查，检测外周血中肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）、T细胞亚群、一氧化氮合酶（iNOS）等的浓度。结果 对照组移植心平均存活时间为（6．0±1．054）d，FK506组为（10．2±2．2）d，SIN组为（9．5±1．84）d，联合组为（16．2±2．1）d，联合组与其他3组比较，差异有统计学意义（P〈0．05）。SIN组、FK506组及联合组与对照组比较，外周血中TNF-α、IFN-γ、iNOS的表达明显减少（P〈0．05），CD4^＋T细胞亚群增殖率也明显下降（P〈0．05）。其中联合组的效果更优于SIN组和FK506组（P〈0．05）。结论 SIN能明显地抑制大鼠心脏移植急性排斥反应的发生，与FK506联合应用有协同作用。     

核因子κB诱骗剂处理的树突状细胞延长小鼠移植心脏存活时间

目的探讨核因子κB（NF-κB）诱骗剂处理供者树突状细胞（DC）对同种异体小鼠移植心脏存活时间的影响。方法在体外以NF-κB诱骗剂处理供者骨髓来源的DC，并于心脏移植术前7d经门静脉输注2×10^6个DC给受者，术后1～7d受者接受亚治疗量的环孢素A（10mg·kg^-1·d^-1）腹腔注射（联合方案组），并设不作任何处理（对照组）、单用环孢素A（CsA组）、单纯输注未经处理DC（DC对照组）和单纯输注经处理DC（DC实验组）的对照组，另设接受来自第三方供者的对照组（第三供者组，受者的处理同联合方案组），所有受者均接受腹腔心脏移植。观察各组移植心脏的存活时间；采用酶联免疫吸附法检测术后第7天受者血清白细胞介素2（IL-2）、IL-4、IL-10和γ干扰素（IFN-γ）的含量。结果移植心脏平均存活时间（MST），对照组为7d，CsA组为10．3d，DC对照组为7．6d，DC实验组为21．4d，联合方案组为53．6d，第三供者组为9d，DC实验组移植心脏MST明显长于对照组和DC对照组，差异有统计学意义（P〈0．01）；联合方案组移植心脏MST明显长于CsA组、DC实验组及第三供者组，差异有统计学意义（P〈0．01）。联合方案组IL-2和IFN-γ的含量最低，而IL-4和IL-10的含量最高，与其它各组比较，差异均有统计学意义（P〈0．05）；与对照组、DC对照组及CsA组相比，DC实验组IL-2及IFN-γ的含量也显著降低（P〈0．05），而IL-4和IL-10则升高（P〈0．05）。结论术前输注经NF-κB诱骗剂处理的供者DC可延长同种小鼠移植心脏的存活时间，若术后加用短程亚治疗量CsA，则移植心脏的存活时间得到进一步延长。     

环孢菌素A抑制大鼠同种心脏移植急性排斥反应中趋化因子受体CCR5表达的研究

目的观察大鼠同种心脏移植急性排斥反应中趋化因子受体CCID的表达及环孢菌素A（CsA）的抑制作用。方法分两组建立同种大鼠颈部心脏移植模型：对照组（n=25）和新山地明组（CsA组，n=25），各5例观察移植心脏存活时间。于移植术后第1、5、7、14天分别取移植心组织各5例，逆转录-聚合酶链反应（RT—PCR）检测移植心组织内趋化因子受体CCR5mRNA不同时间点的表达水平，免疫组织化学方法检测移植心组织内趋化因子受体CCR5分子的表达差异。结果对照组移植心存活时间为（11．6±1．5）d，CsA组移植心存活时间为（22．4±5．1）d，两组问移植心存活时间差异有统计学意义（P〈0．01）。急性排斥组和CsA处理组大鼠移植心脏在术后第5、7、14天都可检测到趋化因子受体CCR5mRNA阳性表达，但CsA处理组趋化因子受体CCRSmRNA的表达明显弱于急性排斥组。同样急性排斥组和CsA处理组大鼠移植心脏在术后第5、7、14天都可检测到趋化因子受体CCR5分子的表达，CsA处理组趋化因子受体CCR5分子的表达相对较弱。结论趋化因子受体CCR5在早期移植免疫事件中具有重要的作用，CsA能部分抑制趋化因子受体CCR5的表达，并与移植物存活时间延长有一定的关系。     

重组人肝细胞生长因子对心脏移植冠状血管内膜内皮型一氧化氮合酶的影响

目的探讨重组人肝细胞生长因子（rh-HGF）对大鼠心脏移植冠状血管内膜内皮型一氧化氮合酶（eNOS）的影响。方法近交系健康雄性Wistar大鼠80只和雄性sD大鼠40只，建立腹腔异位心脏移植模型。实验分3组：同系移植组，异系移植包括对照组和实验组。分别于术后15、60d采集各组标本，沿冠状动脉切取心肌组织，进行免疫组织化学检测冠状血管内膜eNOS的表达，逆转录．聚合酶链反应（RT-PCR）检测冠状血管内膜eNOS mRNA表达，以及观测冠状血管病理变化。结果实验组移植心脏冠状动脉内皮细胞完整，内膜轻度增厚，管腔轻度狭窄，病理改变明显轻于对照组。RT-PCR测定eNOS mRNA在移植心脏冠状动脉内膜的表达，实验组（1．81±0．25）、（1．57±0．24）均明显高于对照组（0．76±0．06）、（0．53±0．04）及同系移植组（0．82±0．06）、（0．89±0．10）表达（P〈0．01）。结论rh-HGF通过上调移植心脏冠状血管内膜eNOS表达，保护冠状血管内皮功能，以预防移植心脏血管病的发生。     

青藤碱和环孢素A联合应用延长大鼠移植心的存活时间

目的探讨青藤碱在大鼠单个核细胞（PBMC）增殖中的作用；观察青藤碱和环孢素A（CsA）联合应用对大鼠心脏移植术后移植心存活时间的影响。方法分离出大鼠外周血单个核细胞，用刀豆蛋白A（ConA）和混合淋巴细胞培养（MLC）激活单个核细胞增殖，采用四甲基偶氮唑盐（MTT）比色法及磷脂酰丝氨酸外翻分析（Annexin V）法检测单纯应用青藤碱或青藤碱＋CsA联合应用后对单个核细胞增殖作用的影响；以Wistar大鼠为供者，SD大鼠为受者，建立改良的颈部异位心脏移植模型，根据术后用药不同将其分为5组。（1）对照组：肌肉注射生理盐水1ml；（2）青藤碱组：肌肉注射青藤碱20mg·kg^-1·d^-1；（3）CsA组：肌肉注射CsA2mg·kg^-1·d^-1;（4）青藤碱＋CsA组：肌肉注射青藤碱20mg·kg^-1·d^-1＋CsA2mg·kg^-1·d^-1；（5）大剂量青藤碱组：肌肉注射青藤碱40mg·kg^-1·d^-1。观察各组移植心存活时间及病理学改变。结果（1）青藤碱能够显著的抑制ConA和MLC激活的单个核细胞增殖，并与CsA有协同作用。（2）青藤碱组及大剂量青藤碱组与对照组比较，移植心存活时间虽延长，但差异无统计学意义（P〉0．05）；青藤碱＋CsA组移植心存活时间明显延长，与其它4组比较，差异均有统计学意义（P〈0．01）。结论青藤碱能够显著的抑制单个核细胞的增殖；青藤碱联合小剂量环孢素A能明显延长移植心存活时间。     

大鼠肝移植后早期血清一氧化氮的变化及其意义

目的探讨大鼠肝移植后早期血清一氧化氮（NO）的变化情况及其意义。方法将SD大鼠随机分成A、B、C三组，进行肝移植．供、受者均为SD大鼠。A组于移植肝恢复血流2h、B组于移植肝恢复血流4h、C组于移植肝恢复血流6h时采取受者的下腔静脉血和左肝叶组织．测定血清丙氨酸转氨酶（ALT）和NO含量．免疫组化法测定移植肝组织中核因子．κB p65亚单位（NF-κB p65）的表达，并观察肝组织病理学变化；每组均于移植肝恢复血流时收集5min的胆汁，测量5min胆汁分泌量。结果A组的5min胆汁分泌量为（3．73±1．11）μl．明显高于B组的（2．35±0．92）μ和C组的（2．23±0．81）μl（P〈0．05）。A组血清ALT含量为（468±36）IU／L．B组为（619±49）IU／L．C组为（820±65）IU／L，A组明显低于B、C组（P〈0．05），B组明显低于C组（P〈0．05）。A组血清NO含量为（14．2±1．5）μmol／L，明显高于B组的（10．5±1．2）μmol／L和C组的（10．3±1．1）μmol／L（P〈0．05）。A组肝组织中NF-κB p65表达阳性细胞百分率为（23．5±1．9）％．B组为（43．8±3．8）％，C组为（48．6±5．1）％．A组明显低于B、C组（P〈0．05）。病理学观察显示．随着移植肝脏再灌注时间的延长，肝组织损伤呈进行性加重。Pearson相关性分析提示．NO与血清ALT水平及NF-κB p65表达呈明显的负相关（r值分别为-0．74和-0．77，P〈0．01）。结论移植肝脏再灌注早期．血清NO下降，NF-κB的活性逐渐增强．移植肝脏的功能和组织损伤呈加重趋势。     

干扰素-α诱导肾癌细胞胸苷磷酸化酶表达对5-FU化疗敏感性的影响

目的 探讨干扰素-α诱导肾癌细胞胸苷磷酸化酶（thymidine phosphorylase，TP）表达对5-氟尿嘧啶（5-FU）化疗敏感性的影响。方法采用不同浓度的干扰素-α2b处理肾癌细胞株786—0，应用RT—PCR和免疫印迹方法分别检测TP mRNA和TP蛋白水平变化。MTT法检测不同处理组786—0细胞中5-FU的半数抑制浓度（IC50）。建立肾透明细胞癌移植瘤动物模型，观察干扰素-α2b联合5-FU化疗对移植瘤生长的影响，免疫组化检测移植瘤中TP的表达，TUNEL检测肿瘤细胞的凋亡。结果 干扰素-α2b3000和6000IU／ml处理组，TP mRNA表达量（灰度峰值）分别为0．5733±0．0231和0．8233±0．0404，TP蛋白表达量分别为0．6347±0．0719和0．8735±0．0640。干扰素-α对TP的表达有剂量依赖性增强作用（P〈0．01）。在干扰素-α2b作用下，5-FU对786—0半数抑制浓度由（13．9467±3．7140）μmol／L下降至（5．3200±0．1039）μmol／L，化疗敏感性增加（P〈0．01）。联合用药组移植瘤体积为（0．0940±0．0492）cm^3，小于单纯5-FU组的（0．5424±0．1591）cm^3（P〈0．05）。单纯5-FU组和联合用药组移植瘤中肿瘤细胞凋亡指数差异无统计学意义（P〉0．05）。结论 干扰素-α2b诱导的TP增强表达参与了干扰素-α联合5-FU化疗增效作用，TP是干扰素-α2b的靶基因之。     

他克莫司和环孢素A防治急性移植物抗宿主病的效果比较

目的比较他克莫司（FK506）和环孢素A（CsA）防治造血干细胞移植后急性移植物抗宿主病（aGVHD）的效果。方法根据所用免疫抑制方案的不同，将118例异基因造血干细胞移植患者分为两组，一组移植后采用以FK506为主的方案预防GVHD（FK506组，n=36例），另一组采用以CsA为主的方案预防GVHD（CsA组，n=82例）。观察两组患者aGVHD的发生情况及治疗效果、造血重建情况、存活率、原发病的复发率以及免疫抑制剂的不良反应。结果FK506组和CsA组aGVHD累积发生率分别为（50．0±8．8）％和（50．7±5．6）％（P〉0．05），Ⅱ～Ⅳ度aGVHD累积发生率分别为（13．0±6．1）％和（31．0±5．2）％（P〈0．05），Ⅲ～Ⅳ度aGVHD累积发生率分别为（2．8±2．7）％和（12．3±3．7）％（P〉0．05）。采用FK506及甲泼尼龙（MP）治疗Ⅰ～Ⅱ度aGVHD的效果优于CsA与MP组合，但差异无统计学意义（P〉0．05），而治疗Ⅲ～Ⅳ度aGVHD，FK506与MP组合明显优于CsA与MP组合（P〈0．05）。两组在造血重建时间、患者存活率、无原发病的存活率以及原发病复发率等方面的差异均无统计学意义。FK506组16．7％患者血糖升高，而CsA组血糖升高者仅占1．2％。结论FK506可有效预防和治疗异基因造血干细胞移植后的aGVHD，其总体效果优于CsA。     

Histochemical and contractile properties of striated muscles of urethra and levator ani of dogs and sheep

AIMS: To understand their possible importance in long- and short-term control of continence, some properties of the striated muscles of the urethra and pelvic floor (levator ani) of dogs and sheep were investigated, especially fiber types and contractile characteristics. MATERIALS AND METHODS: Striated muscles of urethra and levator ani of 29 male and 6 female dogs and 11 male and 6 female sheep were removed and cut into strips. Some strips were frozen and stained for ATPase at pH 9.4 and 4.3 for fiber typing; others were set up in an organ bath to study contractile responses to nerve stimulation. RESULTS: All muscles contained both type I (slow) and type II fibers, ranging from 97% type II in female greyhound urethra to 60% in female sheep levator ani. For each muscle, there were fewer type II muscles in sheep than in dog. The diameters of the urethral fibers were about 60% of the levator ani in dogs and 34% in sheep. Contraction of the urethral muscle was faster than for levator ani and declined to about 80% of the peak, 500 msec after the beginning of stimulation at 20 Hz. The levator ani contraction rose to a steady level as long as stimulation continued. CONCLUSIONS: Both the levator ani and urethral striated muscles contain slow and fast fiber types. The levator ani muscles are capable of sustained contraction with rapid onset which will produce long-term closure of the urethra. The circular urethral muscle contraction was faster but less well maintained.     

Incorporation and release of85Sr and14C-proline-hydroxyproline in mineral and collagen of bone and incisor teeth of growing rats

The extent to which exchange and reutilization processes of mineral tracers affect skeletal mineral accretion and resorption measurements was evaluated by comparing the rates of appearance and disappearance of⁸⁵Sr and¹⁴C-proline-hydroxyproline in bones and teeth in growing rats for 12 days following simultaneous parenteral injection of these tracers. Expressions for the relative rates of collagen synthesis and breakdown, which unlike mineral metabolism are considered not to be complicated by exchange phenomena, were based on¹⁴C-proline conversion to¹⁴C-hydroxyproline; the specific activity of the latter was determined. Both the mineral and the collagen specific activities reflected the rates and patterns of growth of the samples assayed; rapid growth and a short interval of time between formation and resorption of tissue in themetaphyseal bone which contains the cartilagineous growth plate, slow growth and an interval of time between formation and resorption of tissue indiaphyseal bone and incisor teeth which is longer than the 12 days of the experiment. However, in metaphyseal bone the specific activity collagen/mineral ratio dropped by one half during the 4–12 day interval in contrast to diaphyseal bone and incisor teeth in which no change in this ratio was observed during this period of time. The data indicate that collagen in the metaphyseal growth zone is removed by resorption before it has become fully mineralized, and that exchange is a relatively unimportant factor in the long term kinetics of bone mineral.

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Zusammenfassung Das Ausmaß, bis zu welchem Austausch- und Wiederverwendungsprozesse der mineralen Tracer die Messungen des mineralen Skelett-Auf- und Abbaues beeinflussen können, wurde ausgewertet; zu diesem Zweck wurde die Geschwindigkeit des Auftretens und Verschwindens von⁸⁵Sr und von¹⁴C-Prolin-Hydroxyprolin in Knochen und Zähnen von wachsenden Ratten während der 12 auf die simultane parenterale Injektion dieser Tracer folgenden Tage verglichen.Der Ausdruck für die relative Geschwindigkeit des Kollagen-Auf- und Abbaues, bei welchem im Gegensatz zum Mineralmetabolismus kein Mitwirken des Austauschphänomens vermutet wird, basiert auf der Umwandlung von¹⁴C-Prolin zu¹⁴C-Hydroxyprolin; die spezifische Aktivität des letzteren wurde bestimmt.Aus der spezifischen Aktivität des Minerals sowie jener des Kollagens konnten die Geschwindigkeit und die Art des Wachstums der untersuchten Proben ersehen werden, d.h.schnelles Wachstum und ein kurzes Zeitintervall zwischen Bildung und Resorption des Gewebes imKnochen der Metaphyse, die auch die knorpelige Wachstumsplatte enthält, und andererseitslangsames Wachstum und längeres Zeitintervall (länger als die 12 Tage des Experimentes) zwischen Bildung und Resorption des Gewebes imKnochen der Diaphyse und in den Schneidezähnen. Immerhin fiel die spezifische Aktivität des Kollagen/Mineral-Anteils im Knochen der Metaphyse während dem 4–12tägigen Zeitintervall auf die Hälfte, im Gegensatz zum Knochen der Diaphyse und der Schneidezähne, bei welchen während dieser Zeitspanne kein Unterschied in diesem Verhältnis beobachtet wurde.Diese Ergebnisse zeigen, daß Kollagen in der Wachstumszone der Metaphyse durch Resorption verschwindet, bevor es ganz mineralisiert ist, und daß der Austausch ein relativ unwichtiger Faktor in der Kinetik auf lange Sicht des Knochenminerals ist.

     

Instrumented ligamentotaxis and stabilization of compression and burst fractures of dorsolumbar and mid-lumbar spines

Background:

Controversy continues regarding the best treatment for compression and burst fractures. The axial distraction reduction utilizing the technique employing the long straight rod or curved short rod without derotation to reduce fracture are practised together with short segment posterolateral fusion (PLF). Effects of the early postoperative mobilization without posterolateral fusion on reduction maintenance and fracture consolidation were not evaluated so far. The present prospective study is designed to assess the effectiveness of i) reduction and restoration of sagittal alignment, ii) no posterolateral fusion on the reduced, fractured vertebral body and injured disc, iii) fracture consolidation and iv) the fate of the unfused cephalad and caudal injured motion segments of the fractured vertebra.

Materials and Methods:

The study includes 15 Denis burst and two Denis type D compression fractures between T₁₂ and L₃. The lordotic distraction technique was used for ligamentotaxis utilizing the contoured short rods and pedicle screw fixator. Three vertebrae including the fractured one were fixed. The patients after surgery were braced for ten weeks with activity restriction for 2-4 weeks. The patients were evaluated for change in vertebral body height, sagittal curve, reduction of retropulsion, improvement in neural deficit. The unfused motion segments, residual postoperative pain and bone and metal failure were also evaluated.

Results:

The preoperative and postreduction percentile vertebral heights at, zero (immediate postoperative), at three, six and 12 months followup were 62.4, 94.8, 94.6, 94.5 and 94.5%, respectively. The percentages of the intracanal fragment retropulsion at preoperative, and postoperative at zero, 3, 6 and 12 months followup were 59.0, 36.2,, 36.0, 32.3, and 13.6% respectively.The preoperative and postreduction percentile loss of the canal dimension and at zero, three, six and 12 months were 52.1, 45.0, 44.0, 41.0 and 29% respectively suggesting that the under-reduced fragment was being resorbed gradually by a remodeling process. The mean initial kyphosis of 33° became mean 2° immediately after reduction and mean 3° at the final followup. The fractured vertebral bodies consolidated in an average period of ten weeks (range 8-14 weeks). The restored disc heights were relatively well maintained throughout the observation period. All paraparetic patients recovered neurologically. There were no postoperative complications.

Conclusion:

Instrument-aided ligamentotaxis for compression and burst fractures utilizing the short contoured rod derotation technique and the instrumented stabilization of the fractured spine are found to be effective procedures which contribute to the fractured vertebral body consolidation without recollapse and maintain the motion segment function.     

Principles and Practice of Hemofiltration and Hemodiafiltration

There is growing interest in the convective dialysis therapies, hemofiltration (HF) and hemodiafiltration (HDF). Both require dialysis membranes which are highly permeable to solutes as well as fluid, and in both cases large volumes of ultrafiltration are the condition for convective transport. In HDF the convection is combined with diffusion, and as a consequence, maximum clearance over the entire molecular weight spectrum is achieved. Optimal forms of HDF provide urea clearance 10–15% higher than the corresponding diffusive mode. The larger the solute, the greater is the impact of convection, and β₂-microglobulin (β₂m) levels may be up to 70% reduced. Traditional postdilution HF provides high clearance of medium sized and large molecules. Satisfactory clearance of small solutes requires blood flows in excess of 500 ml/min. With access to practically unlimited volumes of substitution solution through on-line ultrafiltration, predilution HF can now be used. This increases the clearance of small solutes to an acceptable range. For HDF as well as HF, large patient populations consistently treated for longer periods of time are needed to make valid outcome comparisons with other therapies.     

骨折不愈合与延迟愈合的成因与治疗

目的探讨骨折不愈合与延迟愈合的成因、报肯治疗的方法与设果。方法对1990年7月～2004年12月间收治的107例骨折不愈台、54例骨折延迟愈合2例先天性胫骨骨不连进行回顾性研究，分析原因，随访治疗结果。18例延迟愈合行保守治疗，本组其他145例行手术治疗，结果除2例先天性胫骨骨不连外，其余161例的成因中均有医源性因素。10例失去随访，153例平均随访17（6-28）个月，骨折均获骨性连接，愈合时间平均10（6-14）个月，肢体功能恢复良好，结论医源性技术缺陷是骨折不愈合与延迟愈合的主要原因，针对各种不同因素进行合理治疗可获得满意效果。     

Recognition and management of phaeochromocytoma and paraganglioma

Phaeochromocytomas and paragangliomas (PPGL) are catecholamine-secreting neuroendocrine tumours arising from the chromaffin cells in the adrenal medulla. These tumours may be identified incidentally, as part of a work-up for multiple endocrine neoplasia or following haemodynamic surges during unrelated procedures. Advances in perioperative management and improved management of intraoperative haemodynamic instability have significantly reduced surgical mortality from around 40% to less than 3%. Surgery is the definitive treatment in most cases and laparoscopic resection where possible is associated with improved outcomes. Anaesthetic management of PPGL cases represents a unique haemodynamic challenge both before and after tumour resection. In this article we describe the physiology of these tumours, their diagnosis, preoperative optimization methods, intraoperative anaesthetic management and management of postoperative complications.     

Physiology and pharmacology of nausea and vomiting

Nausea and vomiting are both very unpleasant experiences. The physiology is poorly understood; however, understanding what we do know is key to tailoring a preventative or therapeutic antiemetic regime. There are two key sites in the central nervous system implicated in the organization of the vomiting reflex: the vomiting centre and the chemoreceptor trigger zone. There are five key neurotransmitters involved in afferent feedback to these areas. These are histamine (H₁ receptors), dopamine (D₂), serotonin (5-HT₃), acetyl choline (muscarinic) and neurokinin (substance P). Postoperative nausea and vomiting will occur in around one-third of elective patients who have no prophylaxis. This can result in many detrimental effects including patient dissatisfaction, unplanned admission and prolonged recovery. It is therefore essential that clinicians understand how they can prevent and treat nausea and vomiting using either a single agent or a combination of antiemetics to target relevant receptors. Commonly used drugs include antihistamines, dopamine antagonists, serotonin antagonists and steroids. More novel agents are being developed such as aprepitant, a neurokinin receptor antagonist, palonosetron, a 5HT₃ receptor antagonist and nabilone, a synthetic cannabinoid.     

Physiology and pharmacology of nausea and vomiting

Nausea and vomiting are both very unpleasant experiences. The physiology is poorly understood; however, understanding what we do know is key to tailoring a preventative or therapeutic antiemetic regime. There are two key sites in the central nervous system implicated in the organization of the vomiting reflex: the vomiting centre and the chemoreceptor trigger zone. There are five key neurotransmitters involved in afferent feedback to these areas. These are histamine (H₁ receptors), dopamine (D₂), serotonin (5-HT₃), acetyl choline (muscarinic) and neurokinin (substance P). Postoperative nausea and vomiting will occur in around one-third of elective patients who have no prophylaxis. This can result in many detrimental effects including patient dissatisfaction, unplanned admission and prolonged recovery. It is therefore essential that clinicians understand how they can prevent and treat nausea and vomiting using either a single agent or a combination of antiemetics to target relevant receptors. Commonly used drugs include antihistamines, dopamine antagonists, serotonin antagonists and steroids. More novel agents are being developed such as aprepitant, a neurokinin receptor antagonist, palonosetron, a 5HT₃ receptor antagonist, and nabilone, a synthetic cannabinoid.