The VenaTech LP permanent caval filter: effectiveness and safety in the prevention of pulmonary embolism--a European multicenter study

PURPOSE: To evaluate (i) the appropriateness, safety, and patient outcomes after placement of the VenaTech LP caval filter and (ii) the success of filter insertion through various venous access routes. MATERIALS AND METHODS: An open multicenter prospective observational study was conducted in 12 European centers, including an initial part limited to four centers. Patients with common indications were eligible for inclusion after approval by an independent ethics committee. Over a 42-month period, 106 patients (46 men [43.4%], 60 women [56.6%]), 72.2 years +/- 13.3 of age (range, 37-97 y), with poor prognoses were included. Patients were examined 2-5 days after the procedure, then at 30 days +/- 5 and 90 days +/- 15 for clinical follow-up and filter assessment. Evaluation criteria were based on occurrence of pulmonary embolism (PE), adverse events, death, filter position, and caval patency. Data were available in 101 case report forms at days 2-5, in 75 at day 30 +/- 5, and in 60 at day 90 +/- 15. Two patients (1.9%) were lost to follow-up. RESULTS: The overall mortality rate was 20.8%. PE was present in 71 patients (67.0%). History of venous thromboembolic disease (VTED) was noted in 32 patients (30.2%), and recently diagnosed VTED was present in 101 patients (95.3%). Partial caval thrombosis was present before the procedure. Filter tilting of 10-45 degrees was seen in 3.9% of cases at days 2-5, 4.3% of cases at day 30 +/- 5, and 1.9% of cases at day 90 +/- 15. Follow-up evidenced neither clinical signs of PE nor significant device-related events. CONCLUSIONS: In a prospective patient cohort with a projected 3-month mortality rate of nearly 21.0% as a result of severe prognoses, the success of insertion via various venous access routes and the appropriateness and safety of the VenaTech LP caval filter were assessed. Findings at 90-day follow-up were free of symptomatic PE and device-related adverse effects.     

Public health nursing practice with 'high priority' families: the significance of contextualizing 'risk'

BROWNE AJ, HARTRICK DOANE G, REIMER J, MacLEOD MLP and McLELLAN E. Nursing Inquiry 2010; 17 : 27–38
Public health nursing practice with 'high priority' families: the significance of contextualizing 'risk'
Public health nurses (PHNs) play a vital role in supporting families at risk; few studies, however, have focused on how PHNs actually work with families to provide support, build trust, and use their clinical judgment to make decisions in complex, at-risk situations. In this study, we report on findings from research that illustrate how PHNs use relational approaches in their work with 'high priority' families. Drawing on data collected from interviews and focus groups with 32 PHNs, we discuss three central features inherent to working relationally with families at risk: (i) contextualizing the complexities of families' lives; (ii) responding to shifting contexts of risk and capacity; and (iii) working relationally with families under surveillance. These findings show that the ability to recognize risk and capacity as intersecting aspects of families' lives, and to practice from a stance that recognizes risk as contextualized is foundational to effective working relationships with high-priority families.     

Accumulation of nicotine and its metabolites in rat brain after intermittent or continuous peripheral administration of [2'-(14)C]nicotine.

Concentrations of nicotine, cotinine, and nornicotine in brain and blood following both intermittent and continuous administration of [2'-(14)C]nicotine to rats were determined to assess nicotine metabolite accumulation in brain following repeated nicotine administration. For intermittent studies, rats were administered s.c. 1 to 10 doses of nicotine (0.3 mg/kg, 15 or 25 microCi of [2'-(14)C]nicotine; 30-min interinjection interval). For continuous administration studies, rats were implanted s.c. with an osmotic minipump delivering nicotine (0.8 mg/kg/day, 25 or 50 microCi of [2'-(14)C]nicotine for 1-21 days). Whole brain and trunk blood was collected. The concentration of [2'-(14)C]nicotine and its metabolites was determined via high-pressure liquid radiochromatography. Brain concentrations of nicotine, cotinine, and nornicotine increased 2-, 12-, and 9-fold, respectively, following 10 injections, reaching a plateau following the fifth injection. Brain blood ratios indicate an enhanced preferential distribution of nornicotine to brain with increasing numbers of injections. Across the 21-day period of continuous infusion, blood nicotine and nornicotine concentrations remained relatively constant, whereas concentrations in brain increased approximately 4-fold. Generally, cotinine concentrations in brain and blood did not change across the infusion period. Brain/blood ratios indicate an increase in nicotine distribution into brain across days of nicotine infusion. Results demonstrate that both nicotine and its metabolites accumulate in brain following repeated nicotine administration, and indicate that brain nicotine concentration can not be extrapolated from plasma cotinine or nicotine concentrations. Thus, nornicotine accumulation following repeated nicotine administration suggests that this metabolite plays a contributory role in the neuropharmacological effects of nicotine.     

Nicotinic receptor modulation of dopamine transporter function in rat striatum and medial prefrontal cortex

Nicotine activates nicotinic acetylcholine receptors (nAChRs) on dopamine (DA) terminals to evoke DA release, which subsequently is taken back up into the terminal via the DA transporter (DAT). nAChRs may modulate DAT function thereby contributing to the regulation of synaptic DA concentrations. The present study determined the dose-response for nicotine (0.1-0.8 mg/kg, s.c.) to modulate DA clearance in striatum and medial prefrontal cortex (mPFC) using in vivo voltammetry in urethane anesthetized rats and determined if this effect was mediated by nAChRs. Exogenous DA (200 microM) was pressure-ejected at 5-min intervals until reproducible baseline signals were obtained. Subsequently, nicotine or saline was administered, and DA pressure ejection continued at 5-min intervals for 60 min. In both striatum and mPFC, signal amplitude decreased by approximately 20% across the 60-min session in saline-injected rats. A monophasic dose-response curve was found in striatum, with a maximal 50% decrease in signal amplitude after 0.8 mg/kg. In contrast, a U-shaped dose-response curve was found in mPFC, with a maximal 50% decrease in signal amplitude after 0.4 mg/kg. Onset of nicotine response occurred 10 to 15 min after injection in both brain regions; however, the amount of time before maximal response was 45 and 30 min in striatum and mPFC, respectively. Mecamylamine (1.5 mg/kg) completely inhibited the nicotine-induced (0.8 and 0.4 mg/kg) decrease in signal amplitude in striatum and mPFC, respectively, indicating mediation by nAChRs. Thus, nicotine enhances DA clearance in striatum and mPFC in a mecamylamine-sensitive manner, indicating that nAChRs modulate DAT function in these brain regions.     

骨关节炎大鼠关节软骨修复与橄榄叶提取物的干预效应

目的:观察橄榄叶提取物对白陶土及鹿角菜胶诱导的大鼠骨关节炎组织炎症的预防作用及对关节软骨的修复作用。方法:试验于2005-11/12在大连医科大学中日合作医药科学研究所进行。实验动物:选择健康雄性SD大鼠80只。实验材料:受试物橄榄叶提取物[由日本国Eisai食品与化学有限公司(日本国东京市)提供]。实验分组及给药:按体质量将大鼠随机分为5组,每组16只。模型对照组,灌胃给予蒸馏水,消炎痛组,灌胃给予消炎痛2mg/kg体质量,其余3组为橄榄叶提取物组,分别给予橄榄叶提取物(活性成分为以羟基酪醇为主的多酚)25,50,100mg/kg体质量灌胃,连续5d。第1天给药后1h,采用白陶土与鹿角菜胶诱发大鼠单发亚急性关节炎。实验评估:①诱发关节炎后1,3,5d,用容积测量法测定每组8只大鼠的左右后肢足跖体积,计算肿胀度,并同时用游标卡尺测定其胫跗骨关节最大径。②诱发关节炎后第5天,测定大鼠足跖伊文思蓝含量。每组的另8只大鼠,在诱发关节炎第5天麻醉后处死,剪下右足跖做组织病理学检查,观察橄榄叶提取物对大鼠骨关节炎中组织炎症的预防作用及对关节软骨的修复作用。结果:80只大鼠全部进入结果分析。①足跖肿胀度及胫跗骨关节径:诱发关节炎后1,3,5d,橄榄叶提取物50mg/kg组和100mg/kg组大鼠的右后足跖肿胀度均明显小于模型对照组大鼠[1d:(46.7±4.2)%,(44.8±6.8)%,(52.5±4.0)%;3d:(40.4±4.8)%,(37.4±5.7)%,(45.0±2.9)%;5d:(34.5±4.8),(31.7±5.3)%,(40.4±4.0)%,P<0.05],橄榄叶提取物25mg/kg体质量组,50mg/kg体质量组,100mg/kg体质量组大鼠的右后胫跗骨关节径与模型对照组大鼠比较差异无显著性(P>0.05)。②足跖伊文思蓝含量:诱发关节炎后第5天,橄榄叶提取物50mg/kg,100mg/kg组大鼠的右后足跖伊文思蓝含量均明显小于模型对照组大鼠(P<0.05)。③组织病理学检查及评分:组织病理学检查可见,与模型对照组比较,橄榄叶提取物50mg/kg组,100mg/kg组大鼠骨关节炎中组织炎症浸润明显减少,软骨组织无破坏,且组织病理学评分也明显小于模型对照组(P<0.05)。结论:橄榄叶提取物在50mg/kg体质量及以上剂量能有效地预防白陶土与鹿角菜胶诱发的大鼠骨关节炎中组织炎症,且对软骨有修复作用。     

腺苷三磷酸结合盒转运蛋白A1在动脉粥样硬化中的作用及其受控特点

目的:分析腺苷三磷酸结合盒转运蛋白A1(ATP binding cassette transport proteion A1,ABCA1)在动脉粥样硬化中的作用及其受控机制。资料来源:以“腺苷三磷酸结合盒转运蛋白A1”为检索词,应用计算机在Pubmed、中文全文数据库CNKI中检索2000-01/2006-11腺苷三磷酸结合盒转运蛋白A1与人有关的期刊文献,前者限定语言种类为英文,后者限定语言种类为中文。资料选择:对英文文献390篇、中文文献58篇初审。纳入标准:①与ABCA1结构及功能有关的文献。②与核受体有关的文献。③与载脂蛋白AⅠ有关的文献。④与ABCA1基因的突变、单核苷酸多态性有关的文献。⑤ABCA1蛋白、核受体、ABCA1基因的突变、单核苷酸多态性与动脉粥样硬化有关的文献。排出标准:①与哮喘、癌症、代谢性疾病有关的文献。②相关文献中内容相似的文献。③综述文献。资料提炼:选取3篇涉及ABCA1结构、功能的基础内容;18篇涉及与核受体的内容;2篇涉及载脂蛋白AⅠ的内容;7篇涉及ABCA1基因的突变、单核苷酸多态性的内容;9篇涉及ABCA1蛋白、核受体、ABCA1基因的突变、单核苷酸与动脉粥样硬化的内容。其中30篇列为参考文献。资料综合:分析了腺苷三磷酸结合盒转运体A1的结构和功能的基本情况;文献显示腺苷三磷酸结合盒转运体A1在动脉粥样硬化发病过程中起重要作用;核受体对腺苷三磷酸结合盒转运体A1的表达有调节,且腺苷三磷酸结合盒转运体A1受基因调控。结论:腺苷三磷酸结合盒转运体A1可能是与动脉粥样硬化密切相关的重要候选基因;深入探讨其机制,有利于开发新药防治动脉粥样硬化。     

N,N'-Alkane-diyl-bis-3-picoliniums as nicotinic receptor antagonists: inhibition of nicotine-evoked dopamine release and hyperactivity

The current study evaluated a new series of N,N'-alkane-diyl-bis-3-picolinium (bAPi) analogs with C6-C12 methylene linkers as nicotinic acetylcholine receptor (nAChR) antagonists, for nicotine-evoked [3H]dopamine (DA) overflow, for blood-brain barrier choline transporter affinity, and for attenuation of discriminative stimulus and locomotor stimulant effects of nicotine. bAPi analogs exhibited little affinity for alpha4beta2* (* indicates putative nAChR subtype assignment) and alpha7* high-affinity ligand binding sites and exhibited no inhibition of DA transporter function. With the exception of C6, all analogs inhibited nicotine-evoked [3H]DA overflow (IC50 = 2 nM-6 microM; Imax = 54-64%), with N,N'-dodecane-1,12-diyl-bis-3-picolinium dibromide (bPiDDB; C12) being most potent. bPiDDB did not inhibit electrically evoked [3H]DA overflow, suggesting specific nAChR inhibitory effects and a lack of toxicity to DA neurons. Schild analysis suggested that bPiDDB interacts in an orthosteric manner at nAChRs mediating nicotine-evoked [3H]DA overflow. To determine whether bPiDDB interacts with alpha-conotoxin MII-sensitive alpha6beta2-containing nAChRs, slices were exposed concomitantly to maximally effective concentrations of bPiDDB (10 nM) and alpha-conotoxin MII (1 nM). Inhibition of nicotine-evoked [3H]DA overflow was not different with the combination compared with either antagonist alone, suggesting that bPiDDB interacts with alpha6beta2-containing nAChRs. C7, C8, C10, and C12 analogs exhibited high affinity for the blood-brain barrier choline transporter in vivo, suggesting brain bioavailability. Although none of the analogs altered the discriminative stimulus effect of nicotine, C8, C9, C10, and C12 analogs decreased nicotine-induced hyperactivity in nicotine-sensitized rats, without reducing spontaneous activity. Further development of nAChR antagonists that inhibit nicotine-evoked DA release and penetrate brain to antagonize DA-mediated locomotor stimulant effects of nicotine as novel treatments for nicotine addiction is warranted.     

AGTR1基因A10208G位点多态性与宁夏地区2型糖尿病与健康人的相关性

目的:糖尿病与心血管疾病可能存在着共同的遗传基础,AT1基因可能是心血管疾病与糖尿病共同的候选基因,人类编码AT1受体基因是AGTR1基因。分析2型糖尿病与健康者AGTR1基因A10208G位点多态性与胰岛素抵抗和β细胞功能之间的关系。方法:选择2005-03/2007-03于银川市第一人民医院内分泌科住院新诊断的2型糖尿病患者127例,符合1999年WHO糖尿病诊断标准,男68例,女59例,平均(54.86 11.05)岁,伴有腹型肥胖的2型精尿病患者105例,不伴有腹型肥胖的2型糖尿病患者22例,所有患者均自愿参加本实验,实验经医院伦理委员会批准。健康对照组人群来自宁夏地区的健康志愿者224名,男117名,女107名,平均(56.68 11.39)岁。所有对象均无血缘关系,且两组人群在性别和年龄上均匹配,各项参数之间无统计学意义。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术分析105例伴有肥胖2型糖尿病患者,22例不伴肥胖的2型糖尿病患者及224例健康对照者AGTR1基因A10208G位点多态性,并测定相应生化指标进行分析。结果:351名受试者均进入结果分析。①腹型肥胖糖尿病组AGTR1基因A10208G位点基因型分布和等位基因频率与健康对照组比较有统计学意义(基因型:x~2=10.85,P<0.01;等位基因:x~2=5.57,P<0.05)。②腹型肥胖糖尿病组携G等位基因患者Homa-IR、Homa-β明显高于非腹型肥胖糖尿病组携G等位基因患者(P<0.05)。结论:①AGTR1基因A10208G位点多态性与2型糖尿病存在相关性,尤其是伴有腹型肥胖的2型糖尿病患者。②AGTR1基因A10208G位点A→G的突变可能参与胰岛素抵抗和胰岛β细胞分泌功能损伤。     

亲体肾及造血干细胞联合移植治疗多发性骨髓瘤并发慢性肾功能衰竭

目的:肾功能不全是多发性骨髓瘤并发肾脏疾病的主要表现且决定其预后,探讨1例多发性骨髓瘤并发慢性肾功能衰竭患者行肾及造血干细胞联合移植的治疗体会。方法:南京中医药大学附属医院于2005-04采用肾及造血干细胞联合移植治疗多发性骨髓瘤并发慢性肾功能衰竭患者1例,男性,46岁,经严格的配型及常规检查,发现其胞兄为适合的亲体供者,经供、受者双方同意,结合病情资料并复习文献,先制订出详细治疗方案,然后行亲体肾及造血干细胞联合移植。结果:①供者术后恢复顺利,术后第7天拆线出院,肾功能正常。②受者肾移植术后第3天,血肌酐降至98.2μmol/L,肌酐清除率为45.7mL/min,肾功能恢复正常;干细胞移植术后第13天,查血红蛋白为54g/L、白细胞为4.0×109L-1、中性粒细胞为1.92×109L-1、血小板为30×109L-1,受者造血功能逐步重建,同时抽血行短片段串联重复的嵌合体监测证实受者造血干细胞基因型为完全供者型,说明受者造血功能和免疫功能重建。结论:肾及造血干细胞联合移植治疗多发性骨髓瘤并发慢性肾功能衰竭是一种可行、有效的方法;供、受者的良好配型是移植进行的必备基本条件;另外,术后初期患者处于完全性免疫缺陷状态,故手术后的消毒、隔离措施和抗感染治疗是移植成功的关键。     

Evidence for antiserotonergic properties of yohimbine

Yohimbine (YOH) is a widely used pharmacological tool employed to produce a selective blockade of alpha 2-adrenergic receptors. In the present study operant behavior was used as a biobehavioral assay to determine the activity of YOH at serotonergic receptors, as indicated by its ability to antagonize the behavioral effects of a serotonergic agonist, lysergic acid diethylamide (LSD). Rats were trained to respond on a Fixed Ratio 15 schedule for food reinforcement. YOH (0.5-5.0 mg/kg) or vehicle and LSD (50 micrograms/kg) were administered (IP) 30 min and immediately prior, respectively, to the 30-min operant session. In a separate study, the ability of YOH (0.5-2.5 mg/kg) to antagonize a higher dose of LSD (100 micrograms/kg) was examined. Relatively low doses of YOH (0.5-1.0 mg/kg) were able to partially, but significantly antagonize the LSD-induced suppression and typical hallucinogen-induced disruption of schedule-controlled responding. These results suggest that YOH, even at moderate doses, may act nonselectively as an antagonist at 5-HT receptors, in addition to its antagonist action at alpha 2-adrenergic receptors. This study demonstrates the utility of operant behavior as a biobehavioral assay to study the receptor mediated action of drugs.