低潮气量和呼气末正压在肝肺综合征患者肝移植期的临床应用

目的:终末期肝硬化患者肝病晚期常合并肝肺综合征,伴随低氧血症出现,在肝移植期间进行针对性的通气治疗和管理,对于降低肝移植期的肺部并发症,甚至降低死亡率具有重要的临床意义。文章综合分析低潮气量和低呼期末正压通气对肝移植期间呼吸治疗的作用及其愈后。资料来源:应用计算机检索1970-01/2007-07MEDLINE及万方数据库有关肝移植期间呼吸治疗方面的文献。中文检索词包括"肝移植,肝肺综合征,潮气量,正压呼吸";英文检索词有"liver transplantation,hepato-pulmonary zsyndrome,Tidal ventilation,end-expiratory positive pressure mechanical ventilation"。包括临床研究(不限观察对象的年龄、性别、种族)和基础研究,不限体内或体外研究。资料选择:共收集到1310篇文献,阅读全部文章的文题和大部分文章的摘要,选择肝肺综合征病理改变和通气治疗方面的文献。排除重复性研究和Meta分析类文章。资料提炼:共得到符合纳入条件的文献159篇,排除1141篇。选择其中27篇英文文献及4篇中文文献进行分析。资料综合:①肝肺综合征发病机制错综复杂,术中血流动力学变化及新肝期内毒素、炎性介质、内环境改变等均易发生顽固性低氧血症,甚至出现通透性肺水肿,导致呼吸和心功能衰竭。这些变化是多因素共同作用的结果,在众多发病机制中,肺不张、门肺分流、通气减少或灌流增加均可使通气/灌流比值降低,是导致低氧血症的重要原因。②目前关于肝肺综合征主要是药物处理文献较多,但呼吸治疗报道尚未见到。③根据临床表现术前动脉血氧分压<60mmHg(1mmHg=0.133kPa),动脉二氧化碳分压在正常范围,以及新肝期供肝炎性介质释放,类似于急性呼吸窘迫综合征,因此临床处理均采用呼吸治疗,小潮气量和呼气末正压治疗效果及预后较好。结论:肝肺综合征患者肝移值围手术期应用小潮气量和呼气末正压机械治疗,可降低术后肺部并发症和重症监护时间。     

骨纤维结构不良的诊断和治疗进展

目的:对长期以来关于骨纤维结构不良大量相关研究及文献进行回顾,综述骨纤维结构不良的诊断和治疗的最新进展。资料来源:通过计算机互联网检索OVID数据库1966-01/2006-10关于骨纤维结构不良的文献,检索词:Osteofibrous dysplasia,限定语言种类为English。同时检索1994-01/2006-10中国全文期刊数据库有关骨纤维结构不良的文献,检索词为:骨纤维结构不良,限定语言种类为中文。资料选择:选择与骨纤维结构不良相关的观察对比研究、经验总结、个案报道、最新研究进展等文献,力求资料全面,排除重复研究。资料提炼:共收集相关国内外文献41篇,排除重复性研究11篇,采用30篇,包括关于骨纤维结构不良定义、发病机制、病理、诊断及治疗等。资料综合:①骨纤维结构不良是一种起源于纤维组织的良性骨肿瘤。发病率低、误诊率高。目前具体发病机制不明,现认为与常染色体显性遗传有关。②骨纤维结构不良好发于胫骨,症状为局部肿块。特征性影像学表现为胫骨中段前侧皮质膨胀性密度减低。确诊方法为病理检查。重点与骨纤维异常增殖症、造釉细胞瘤相鉴别,现有大量研究证明该病与造釉细胞瘤有联系。③治疗上过去认为10岁以前应保守治疗,10岁后选择手术治疗,目前倾向于早期骨膜外切除手术治疗。结论:骨纤维结构不良发病率低,对该病认识较少,误诊率较高,重点需与骨纤维异常增殖症、造釉细胞瘤相鉴别,应提高对该病的认识与重视程度,对可疑者行病理检查,确诊者行骨膜外切除,切除范围较大的病例行重建手术。     

Donor sepsis is not a contraindication to cadaveric organ donation

Systemic donor infection is regarded as being an absolute contraindication to cadaveric organ donation for transplantation. This is largely due to fear of transmitting pathogenic organisms to the immunosuppressed recipient. However, due to the current shortage of organs available for transplantation, clinicians are faced with the option of using organs from 'non-ideal' donors, such as those patients with documented evidence of infection. We report the successful outcome of six orthotopic liver transplants, 11 renal transplants, one combined heart lung transplant and one simultaneous kidney and pancreas transplant with organs from eight donors in whom bacterial meningitis (n = 7) and acute bacterial epiglottitis (n = 1) were the antecedent causes of death.      

FcR gamma-chain is essential for both surface expression and function of human Fc gamma RI (CD64) in vivo

Most Ig receptors exist as hetero-oligomeric complexes with separate ligand binding (alpha) and signal transducing (beta, gamma, or zeta) subunits. For Fc gamma RIIIa and Fc epsilon RI, association with the FcR gamma-chain is essential for surface expression. However, the human high affinity IgG receptor, hFc gamma RI, was found to be surface- expressed by itself in transient transfection models. We have now analyzed the integrity of hFc gamma RI expression in more detail in stable transfectants. In vitro we noted that, in the absence of FcR gamma-chain, surface expression of hFc gamma RI rapidly declined to background levels, in both IIA1.6 B cells and NIH3T3 fibroblasts. The effect of FcR gamma-chain on hFc gamma RI surface expression in vivo was evaluated by using two newly generated transgenic mouse lines, selectively expressing hFc gamma RI on myeloid cells. These transgenic mice were crossed with FcR gamma-chain-deficient mice. Analysis of blood monocytes and peritoneal macrophages showed that surface expression of hFc gamma RI was reduced by approximately 80%. The remaining approximately 20% of receptors were still capable of binding IgG-opsonized RBC, suggesting FcR gamma-chain not to be critical for hFc gamma RI ligand-binding capacity. Importantly, however, hFc gamma RI signaling capacity was lost in FcR gamma-chain-deficient cells. No phagocytosis could be observed using either ligand sensitized (EA- IgG2a) or CD64-targeted erythrocytes (using a bispecific antibody) in both hFc gamma RI transgenic lines. This documents the FcR gamma-chain to be indispensable for both surface membrane expression and function of human Fc gamma RI in vivo.     

Knowledge of pressure ulcer prevention: a cross-sectional and comparative study among nurses

Background  

Pressure ulcers are a common, painful and costly condition. Results of a 1991 study into the knowledge among Dutch hospital nurses on the usefulness of measures to prevent pressure ulcers showed moderate knowledge. Results were confirmed by subsequent studies. In recent years, Dutch guidelines have been updated and the attention given to pressure ulcer care has been increased. This was expected to improve pressure ulcer care and to increase nurses' knowledge. The aims of the current study were to investigate (1) how much nurses employed in Dutch hospitals know about the usefulness of 28 preventive measures considered in the most recent national pressure ulcer guideline; (2) whether differences in knowledge exist between nurses working in hospitals that audit pressure ulcers and those employed in hospitals that do not; and (3) to study whether knowledge among Dutch hospital nurses regarding the usefulness of preventive measures had changed between 1991 and 2003.     

Biochemical and behavioural characterization of EMPA,a novel high-affinity,selective antagonist for the OX2 receptor

Background and purpose:

The OX₂ receptor is a G-protein-coupled receptor that is abundantly found in the tuberomammillary nucleus, an important site for the regulation of the sleep-wake state. Herein, we describe the in vitro and in vivo properties of a selective OX₂ receptor antagonist, N-ethyl-2-[(6-methoxy-pyridin-3-yl)-(toluene-2-sulphonyl)-amino]-N-pyridin-3-ylmethyl-acetamide (EMPA).

Experimental approach:

The affinity of [³H]EMPA was assessed in membranes from HEK293-hOX₂-cells using saturation and binding kinetics. The antagonist properties of EMPA were determined by Schild analysis using the orexin-A-or orexin-B-induced accumulation of [³H]inositol phosphates (IP). Quantitative autoradiography was used to determine the distribution and abundance of OX₂ receptors in rat brain. The in vivo activity of EMPA was assessed by reversal of [Ala¹¹,D-Leu¹⁵]orexin-B-induced hyperlocomotion during the resting phase in mice and the reduction of spontaneous locomotor activity (LMA) during the active phase in rats.

Key results:

[³H]EMPA bound to human and rat OX₂-HEK293 membranes with K_D values of 1.1 and 1.4 nmol·L⁻¹ respectively. EMPA competitively antagonized orexin-A-and orexin-B-evoked accumulation of [³H]IP at hOX₂ receptors with pA₂ values of 8.6 and 8.8 respectively. Autoradiography of rat brain confirmed the selectivity of [³H]EMPA for OX₂ receptors. EMPA significantly reversed [Ala¹¹,D-Leu¹⁵]orexin-B-induced hyperlocomotion dose-dependently during the resting phase in mice. EMPA, injected i.p. in rats during the active phase, reduced LMA dose-dependently. EMPA did not impair performance of rats in the rotarod procedure.

Conclusions and implications:

EMPA is a high-affinity, reversible and selective OX₂ receptor antagonist, active in vivo, which should prove useful for analysis of OX₂ receptor function.     

Regulation by FK506 and rapamycin of Ca2+ release from the sarcoplasmic reticulum in vascular smooth muscle: the role of FK506 binding proteins and mTOR

Background and purpose:

The sarcoplasmic reticulum (SR), regulates the cytoplasmic Ca²⁺ concentration ([Ca²⁺]_cyto) in vascular smooth muscle. Release from the SR is controlled by two intracellular receptor/channel complexes, the ryanodine receptor (RyR) and the inositol 1,4,5-trisphosphate receptor (IP₃R). These receptors may be regulated by the accessory FK506-binding protein (FKBP) either directly, by binding to the channel, or indirectly via FKBP modulation of two targets, the phosphatase, calcineurin or the kinase, mammalian target of rapamycin (mTOR).

Experimental approach:

Single portal vein myocytes were voltage-clamped in whole cell configuration and [Ca²⁺]_cyto measured using fluo-3. IP₃Rs were activated by photolysis of caged IP₃ and RyRs activated by hydrostatic application of caffeine.

Key results:

FK506 which displaces FKBP from each receptor (to inhibit calcineurin) increased the [Ca²⁺]_cyto rise evoked by activation of either RyR or IP₃R. Rapamycin which displaces FKBP (to inhibit mTOR) also increased the amplitude of the caffeine-evoked, but reduced the IP₃-evoked [Ca²⁺]_cyto rise. None of the phosphatase inhibitors, cypermethrin, okadaic acid or calcineurin inhibitory peptide, altered either caffeine- or IP₃-evoked [Ca²⁺]_cyto release; calcineurin did not contribute to FK506-mediated potentiation of RyR- or IP₃R-mediated Ca²⁺ release. The mTOR inhibitor {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002, like rapamycin, decreased IP₃-evoked Ca²⁺ release.

Conclusions and implications:

Ca²⁺ release in portal vein myocytes, via RyR, was modulated directly by FKBP binding to the channel; neither calcineurin nor mTOR contributed to this regulation. However, IP₃R-mediated Ca²⁺ release, while also modulated directly by FKBP may be additionally regulated by mTOR. Rapamycin inhibition of IP₃-mediated Ca²⁺ release may be explained by mTOR inhibition.     

Oxidative degradation of cholesteryl esters in low-density lipoproteins: analysis by liquid chromatography-light scattering and protection by a new synthetic antioxidant, S20478

Summary— Cholesteryl esters in the hydrophobic core of low-density lipoprotein (LDL) particles constitute a major molecular target during copper-mediated oxidation. To facilitate the rapid analysis and quantitation of the oxidative degradation of LDL cholesteryl esters, we describe a new approach based on light scattering detection following separation by HPLC. We have applied this approach to the evaluation of the protective capacity of a new synthetic antioxidant, S20478, during oxidation of LDL in the presence of copper ions. HPLC separation of cholesterol and the four major molecular species of cholesteryl esters (C16:0, C18:1, C18:2 and C20:4) of LDL was achieved in a single run of 20 min with high sensitivity (50 ng) and low background. Time course studies of the oxidative modification of LDL (ratio LDL protein: copper, 100 μg/mL: 1μM) revealed that the content of unsaturated cholesteryl esters (C20:4 and C18:2) decreased (–30% and –15%, respectively) within 90 min of copper-mediated oxidation, while only minor degradation (up to 15%) of monounsaturated (C18:1) and saturated (C16:0) esters occurred. At 24 hours of oxidation, only traces (< 5%) of the C20:4 and C18:2 esters were detectable; whereas 52% of the C18:1 ester remained (P < 0.01). Of the saturated esters, only minor proportions (35% or less) underwent oxidative modification. In addition, some 81% of free cholesterol was conserved as the native sterol. The synthetic antioxidant, S20478 (50 μM) was capable of inhibiting the initiation and the propagation of copper-mediated LDL oxidation as determined by the time- and dose-dependant inhibition of the formation of conjugated dienes and thiobarbituric acid-reactive substances, as well as the conservation of the net electrical charge of LDL; indeed S20478 conserved cholesteryl esters in their native form up to 24 hours. However, after prolonged exposure to copper ions (48 hours), only 47% of the unsaturated esters remained (C18:2, P < 0.05). Nonetheless, S20478 (10 μM) was more efficient in inhibiting copper-mediated LDL oxidation as compared to probucol at the same concentration. These findings suggest that S20478 may be of potential interest in a new antioxidant approach to therapeutic stabilisation and regression of atherosclerotic plaques. Moreover, this method should prove useful in the assessment of the integrity of native LDL, and provides a new chemical marker of the degree of LDL oxidation.