Modification by dopaminergic drugs of choice behavior under concurrent schedules of intravenous saline and food delivery in monkeys

The allocation of "choice" behavior provides a measure that may be useful in developing experimental models of clinical relapse. In the present experiments, indirect monoaminergic agonists [cocaine, 1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl)piperazine (GBR 12909), desipramine, and citalopram], and dopaminergic D1 family agonists [(+/-)-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF 82958), R-(+)-6-bromo-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (R-(+)-6-BrAPB), and 6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF 83959)] and D2 family agonists [quinelorane, R-(-)-10,11-dihydroxy-N-n-propylnorapomorphine (R-NPA), (+)-N-propyl-hydroxynaphoxazine [(+)-PHNO], and S-(+)-(4aR,10bR)-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano-[4,3-b]-1,4-oxazin-9-ol (PD 128907)] were evaluated for their capacity to alter the distribution of choice behavior in cocaine-experienced monkeys. Rhesus monkeys responded on two levers (injection-lever and food-lever) under concurrent fixed ratio 30; fixed ratio 30 schedules of i.v. cocaine and food delivery. Under training conditions, the distribution of behavior was related to the unit dose of i.v. cocaine: when saline was available, responding occurred predominantly on the food-lever and when reinforcing doses of cocaine were available, responding occurred predominantly on the injection-lever. Drugs were studied by administering i.m. pretreatment doses before components in sessions of i.v. saline availability. Cocaine produced dose-related increases in injection-lever responding in all monkeys, whereas desipramine failed to alter the distribution of behavior in any monkey. The dopamine transport blocker GBR 12909 and each dopamine D1 family agonist markedly increased injection-lever responding in three of four monkeys; the serotonin transport blocker citalopram and D2 family agonists were comparably effective in only one or two monkeys. These results agree with previous findings of similarity in the behavioral effects of cocaine and indirect or direct dopamine agonists and suggest, furthermore, that i.v. self-administration behavior engendered by priming doses of cocaine may involve actions mediated through both D1 and D2 families of dopamine receptors.     

高频宽景成像超声在战士训练伤中的诊断意义

目的：探讨高频宽景成像超声在战士训练伤中的诊断意义。方法：对驻地120名因训练伤前来就诊的战士进行超声检查，其影像结果均经MR或临床证实。结果：高频超声对液性病变的诊断符合率为100%，具有独特的优势；在肌肉及肌腱的损伤诊断中，符合率分别为77.4%和92.6%。结论：超声检查操作简单，携带方便，在战时、野外或无昂贵检查设备的条件下，超声成为应急诊断的重要手段之一。     

维生素C对大鼠实验性根尖周炎影响的初步研究

目的：探讨维生素 C 对大鼠实验性根尖周炎形成过程的影响。方法：选用100只8周龄 Wistar雄性大鼠，髓腔直接暴露法建立根尖周炎模型，将大鼠分成维生素 C 干预组（0．1、0．5、1．0 mg/mL 维生素 C 灌胃）及对照组，术后1、3、7、14、21 d处死，通过 X线测量法和 HE 染色观察根尖周病变的大小和组织学变化。结果：维生素 C 干预组和对照组根尖透射区的面积从3 d开始增大，呈时间依赖性，21 d时透射面积到达高峰。术后7、14、21 d维生素C 干预组的根尖透射区的面积均小于对照组，差异具有统计学意义（P＜0．05），其中0．1 mg/mL组根尖透射区的面积明显小于其它各组（P＜0．05）。术后7、14、21 d 维生素 C 干预各组骨吸收陷窝数及牙槽骨破坏范围均小于对照组。结论：全身应用维生素 C 对抑制大鼠根尖周炎的进展有一定的作用。     

Implementation of a multidisciplinary guideline‐driven approach to the care of the extremely premature infant improved hospital outcomes

Aim: To test the hypothesis that implementing guidelines for the standardized care of the extremely premature infant (<27 weeks) in the first week of life would improve patient outcomes in an all referral NICU. Methods: Data were collected on all infants <27 weeks gestational age and <7 days of age on admission cared for using these small baby guidelines (SBG), as well as on all age‐matched infants admitted the year prior (comparison). Results: Thirty‐seven patients were cared for utilizing the SBG and 40 patients were in the comparison group. There were no differences between the groups in gestational age, birthweight or age on admission. There was no difference in survival to discharge (73% SBG, 70% comparison). The mean length of stay for survivors was 112 ± 38 days SBG and 145 ± 76 days (p < 0.05) comparison group. Survival without BPD was greater in the SBG group (24%) than in the comparison group (9%; p < 0.05), and survival without severe IVH was greater in the SBG group (65%) than in the comparison group (38%; p < 0.01). Conclusions: These data demonstrate that applying a unified approach to the care of the extremely premature infant in the first week of life resulted in a decrease in the length of hospitalization and improved patient outcomes.     

男性生殖器疣中人乳头瘤病毒基因分型研究进展

人乳头瘤病毒(HPV)感染是全球最常见的性传播疾病(STD)之一。近年来研究证实HPV感染与男性生殖器疣和恶性肿瘤同样具有密切关系。本文就男性HPV感染的近况以及HPV的基因分型在男性生殖器疣中的研究进展作一综述。     

Anemia and blood transfusion and outcome on the intensive care unit

The observation of Sakr and colleagues that transfusion may be beneficial in certain subgroups of intensive care unit (ICU) patients [1] is interesting, since large observational studies demonstrate that transfusion is independently associated with an increased risk of death [2]. Also, a systematic review showed that the benefits of transfusion in the ICU do not outweigh the risks [3]. Sakr and colleagues ascribe their discrepant results to the fact that transfused blood was leukoreduced. Of the 17 randomized controlled trials on the association of nonleukoreduced blood with mortality, however, a benefit of leukoreduction was found only in cardiac surgery patients [4]. A meta-analysis confirmed that available evidence does not justify universal leukoreduction [5].     

Novel effects mediated by bradykinin and pharmacological characterization of bradykinin B2 receptor antagonism in human synovial fibroblasts

Background and purpose:

Bradykinin (BK) and B₂ receptors have been implicated in the pathophysiology of osteoarthritis (OA), and synovitis is one of its hallmarks. Here, the selective B₂ receptor antagonists MEN16132 and icatibant have been pharmacologically characterized in human synovial cells.

Experimental approach:

Radioligand and functional studies (inositol phosphate (IP) accumulation, interleukin (IL)-6 and IL-8 release) were performed in cultured synoviocytes.

Key results:

[³H]-BK saturation studies indicated receptor density (B_max) and K_d values of 121 550 sites per cell and 1.14 nM respectively. In synoviocytes, MEN16132 (pK_i 8.9) was threefold more potent than icatibant (pK_i 8.4). Both antagonists showed competitive antagonism in the BK-induced IP assay (control EC₅₀ 0.45 nM), with pK_B values of 9.9 (MEN16132) and 8.1 (icatibant). 24h incubation with BK induced IL-6 (EC₅₀ 216 nM) and IL-8 (EC₅₀ 53 nM) release. Both MEN16132 (IL-6: pIC₅₀ 8.1; IL-8: pIC₅₀ 8.4) and icatibant (IL-6: pIC₅₀ 6.6; IL-8: pIC₅₀ 6.7) completely prevented this BK-induced release. Indomethacin did not affect the basal or the IL-6/IL-8 release induced by BK, whereas nordihydroguaiaretic acid decreased the basal release, although BK still increased IL-6 and IL-8 production. BK-induced IL-8 release was attenuated by inhibitors of phospholipase C ({"type":"entrez-nucleotide","attrs":{"text":"U73122","term_id":"4098075","term_text":"U73122"}}U73122), p38 (SB203580), JNK (SP600125), ERK 1/2 (PD98059) MAPKs, phosphoinositide 3-kinase ({"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002), NF-κb (BAY-117085) and by the glucocorticoid dexamethasone.

Conclusions and implications:

Bradykinin via B₂ receptors can participate in inflammatory events in synovitis. MEN16132 is a highly potent B₂ receptor antagonist capable of blocking pro-inflammatory responses to BK evoked in human synoviocytes.     

Congenital gastrointestinal defects in Down syndrome: a report from the Atlanta and National Down Syndrome Projects

We report Down syndrome (DS)-associated congenital gastrointestinal (GI) defects identified during a 15 year, population-based study of the etiology and phenotypic consequences of trisomy 21. Between 1989 and 2004, six sites collected DNA, clinical and epidemiological information on live-born infants with standard trisomy 21 and their parents. We used chi-squared test and logistic regression to explore relationships between congenital GI defects and infant sex, race, maternal age, origin of the extra chromosome 21, and presence of a congenital heart defect. Congenital GI defects were present in 6.7% of 1892 eligible infants in this large, ethnically diverse, population-based study of DS. Defects included esophageal atresia/tracheoesophageal fistula (0.4%), pyloric stenosis (0.3%), duodenal stenosis/atresia (3.9%), Hirschsprung disease (0.8%), and anal stenosis/atresia (1.0%). We found no statistically significant associations between these defects and the factors examined. Although not significant, esophageal atresia was observed more often in infants of younger mothers and Hispanics, Hirschsprung disease was more frequent in males and in infants of younger mothers and blacks, and anal stenosis/atresia was found more often among females and Asians.     

Valuing the benefit of diagnostic testing for genetic causes of idiopathic developmental disability: willingness to pay from families of affected children

Idiopathic developmental disability (DD) has been found to put significant psychological distress on families of children with DD. The cause of the disability, however, is unknown for up to one-half of the affected children. Chromosomal abnormalities identified by cytogenetic analysis are the most frequently recognized cause of DD, although they account for less than 10% of cases. Array genomic hybridization (AGH) is a new diagnostic tool that provides a much higher detection rate for chromosomal imbalance than conventional cytogenetic analysis. This increase in diagnostic capability comes at greater monetary costs, which provides an impetus for understanding how individuals value genetic testing for DD. This study estimated the willingness to pay (WTP) for diagnostic testing to find a genetic cause of DD from families of children with DD. A discrete choice experiment was used to obtain WTP values. When it was assumed that AGH resulted in twice as many diagnoses and a 1-week reduction in waiting time compared with conventional cytogenetic analysis, this study found that families were willing to pay up to CDN$1118 (95% confidence interval, $498–1788) for the expected benefit. These results support the conclusion that the introduction of AGH into the Canadian health care system may increase the perceived welfare of society, but future studies should examine the cost-benefit of AGH vs cytogenetic testing.