Inhibition of thromboxane biosynthesis in splanchnic ischemia shock

Administration of dazoxiben (5 mg/kg, i.v.), which effectively suppressed plasma thromboxane concentrations, decreased the number of dogs that deteriorated into shock following a temporary (3-hr) splanchnic artery occlusion (SAO). Dazoxiben pretreatment also moderated the rise of plasma prostacyclin, but it augmented circulating prostaglandin E2 following the release of SAO. These alterations in arachidonic acid metabolism were accompanied by a moderation in the rise of plasma beta-glucuronidase activity, suggesting a moderation of tissue damage in the ischemic splanchnic region, and mitigation of the progressive hemodynamic deterioration caused by the SAO. The possible existence of causal relationships between the plasma eicosanoid concentrations, extent of damage in the ischemic splanchnic region, hemodynamic deterioration, and ultimate production of circulatory failure in dogs subjected to SAO are discussed.     

CGS 21680C, an A2 selective adenosine receptor agonist with preferential hypotensive activity

CGS 21680C (2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethyl-carboxamido adenosine) a 2-substituted analog of the riboside uronamide, 5'-N-ethylcarboxamido adenosine and the related analog CGS 21577 (2-phenethylamino-5'-N-ethylcarboxamido adenosine), have high in vitro affinity for brain striatal adenosine A2 receptors (IC50 values = 22 and 13 nM, respectively). Both compounds were considerably less active at A1 receptors with CGS 21577 and CGS 21680C having respective IC50 values of 0.76 and 3.1 microM. The former compound was thus 59-fold selective for A2 receptors whereas CGS 21680C was 140-fold selective. In contrast, the reference A2 selective ligand, CV 1808 (2-phenylaminoadenosine), showed only 8-fold selectivity as an A2 ligand, having an IC50 of 115 nM in the [3H]-5'N-ethylcarboxamide adenosine assay and an IC50 of 910 nM at the N6-[3H] cyclohexyladenosine site. Further examination of CGS 21680C showed that the compound was without effect on binding to 17 other putative neurotransmitter/neuromodulator sites indicating its selectivity as an adenosine receptor ligand. In an isolated perfused working rat heart model, CGS 21680C effectively increased coronary flow with an ED25 value of 1.8 nM. The corresponding value for CGS 21577 was 3 nM whereas that for CV 1808 was 110 nM. The EC25 for eliciting bradycardia for all three compounds was greater than 1000 nM. The effects of all three compounds could be reversed by treatment with the xanthine adenosine antagonist, xanthine amine congener.(ABSTRACT TRUNCATED AT 250 WORDS)     

青少年和成年人无症状阻生智齿干预措施的疗效评价

目的评价在青少年和成人中拔除与保留无症状阻生智齿的效果.方法计算机检索Cochrane口腔健康组资料库(至2004年8月4日),Cochrane中心临床对照试验资料库(CENTRAL),Ovid-MEDLINE(1966～2004年8月4日),PubMed(1966～2004年8月4日)和EMBASE(1974～2004年8月4日).检索无语种限制.同时对主要相关杂志进行手检,并尽力获取正在进行和未发表的研究.纳入比较预防性拔除与保留阻生智齿效果的全部随机对照或临床对照研究.由3位作者分别独立评价所检出文献的相关性、真实性并提取数据,如有不确定性,联系作者以获取关于随机和失访的更多信息.对所有试验均进行了质量评价.结果共纳入3个研究,其中2个已完成的随机对照试验评价了青少年预防性拔除智齿对切牙拥挤的影响,另1个随机对照试验正在进行,但研究者不能提供任何资料,他们准备近期发表文章,如是,其资料将被纳入本评价的更新中.已完成的2个研究结局判断指标不同,不能进行数据合并.结论没有证据支持或反对常规预防性拔除成年人无症状阻生智齿,有一些可靠的证据表明在青少年预防性拔除阻生智齿既不能减少也不能预防切牙拥挤.     

Thrombin generation during cardiopulmonary bypass: the possible role of retransfusion of blood aspirated from the surgical field

BACKGROUND: In spite of using heparin-coated extracorporeal circuits, cardiopulmonary bypass (CPB) is still associated with an extensive thrombin generation, which is only partially suppressed by the use of high dosages of heparin. Recent studies have focused on the origins of this thrombotic stimulus and the possible role of retransfused suctioned blood from the thoracic cavities on the activation of the extrinsic coagulation pathway. The present study was designed to find during CPB an association between retransfusion of suctioned blood from the pericardium and pleural space, containing activated factor VIIa and systemic thrombin generation. METHODS: Blood samples taken from 12 consenting patients who had elective cardiac surgery were assayed for plasma factor VIIa, prothrombin fragment 1+2 (F1+2), and thrombin-antithrombin (TAT) concentrations. Blood aspirated from the pericardium and pleural space was collected separately, assayed for F1+2, TAT, and factor VIIa and retransfused to the patient after the aorta occlusion. RESULTS: After systemic heparinization and during CPB thrombin generation was minimal, as indicated by the lower than base line plasma levels of F1+2, and TAT after correction for hemodilution. In contrast, blood aspirated from the thoracic cavities had significantly higher levels of factor VIIa, F1+2, and TAT compared to the simultaneous samples from the blood circulation (P < 0.05). Furthermore, after retransfusion of the suctioned blood (range, 200-1600 mL) circulating levels of F1+2, and TAT rose significantly from 1.6 to 2.9 nmol/L (P = 0.002) and from 5.1 to 37.5 μg/L (P = 0.01), respectively. The increase in both F1+2, and TAT levels correlated significantly with the amount of retransfused suctioned blood (r = 0.68, P = 0.021 and r = 0.90, P = 0.001, respectively). However, the circulating factor VIIa levels did not correlate with TAT and F1+2 levels. CONCLUSIONS: These data suggest that blood aspirated from the thoracic cavities during CPB is highly thrombogenic. Retransfusion of this blood may, therefore, promote further systemic thrombin generation during CPB.     

Discriminant validity of the MASQ in a clinical sample

A major weakness of the Mood and Anxiety Symptom Questionnaire (MASQ) is that its discriminant validity has not been demonstrated in a clinical population of anxiety and mood disorder patients. This paper, using 470 anxiety and mood disorder patients, assessed the discriminant validity of the MASQ. The MASQ subscales showed statistically significant discriminant validity, but their maximum ability to discriminate is low at 70%. Overall it was concluded that the MASQ had very weak clinical utility in differentiating anxiety and mood disorder patients, and gave rise to doubts as to the tripartite structure of the MASQ. When using the MASQ, future researchers should be mindful of its limitations when applied in a clinical population.     

A test of the cognitive content specificity hypothesis in depression and anxiety

The present study tested the cognitive content specificity hypothesis (CCSH) to assess whether anxiety and depression can be differentiated on the basis of cognitive disturbance. One hundred and thirty five depressed participants were administered the Beck depression inventory (BDI), the Beck anxiety inventory (BAI), the automatic thoughts questionnaire (ATQ) and the anxious self-statements questionnaire (ASSQ). It was hypothesised that depressive cognitions would be specifically related to, and predictive of, depressive (but not anxiety) symptoms in a depressed sample. Conversely, it was predicted that anxiety cognitions would be specifically related to, and predictive of, anxiety (but not depressive) symptoms in a depressed sample. Results revealed that the ATQ was the sole predictor of the BDI and similarly, the ASSQ was the sole predictor of the BAI. These findings support the CCSH in depression and provide an integrative framework for a greater understanding of the relationship between anxiety and depression.     

Decreased intraperitoneal disease recurrence in epithelial ovarian cancer patients receiving intraperitoneal consolidation treatment with yttrium-90-labeled murine HMFG1 without improvement in overall survival

This study analyzes the site of disease recurrence in ovarian cancer patients to assess the influence of a single intraperitoneal (IP) administration of yttrium-90-labeled murine monoclonal antibody HMFG1 ((90)Y-muHMFG1) on the pattern of disease recurrence. In a large phase III trial ovarian cancer patients in complete clinical remission with FIGO stage Ic-IV were randomized between standard treatment plus a single IP (90)Y-labeled muHMFG1 versus standard treatment alone after negative second-look laparoscopy. Case report forms of all patients with disease recurrence were reviewed to determine site and date of recurrent disease. In total 447 patients were included in the study with a median follow-up of 3.5 years. Relapse was seen in 104/224 in the active and 98/223 in the control arm. Significantly fewer IP (p < 0.05) and more extraperitoneal (p < 0.05) relapses occurred in the active treatment arm. Time to IP recurrence was significantly longer (p = 0.0019) and time to extraperitoneal recurrence was significantly shorter for the active treatment arm (p < 0.001). The impact of IP radioimmunotherapy on IP relapse-free survival could only be seen in the subgroup of patients with residual disease after primary surgery (HR, 0.31; 95% CI, 0.18 to 0.53; p = 0.002). Although, there is no survival benefit for IP radioimmunotherapy as consolidation treatment for epithelial ovarian cancer, we found an improved control of IP disease, that was offset by increased extraperitoneal recurrences.     

MRP8/14 does not contribute to dissemination or inflammation in a murine model of Lyme borreliosis

Myeloid-related protein (MRP)8 and MRP14 form a complex (MRP8/14) that is released by activated neutrophils and monocytes during infection. MRP8/14 has been shown to have bacteriostatic activity in vitro against Borrelia burgdorferi, the spirochete that causes Lyme borreliosis. Furthermore, levels of MRP8/14 have been shown to be elevated in the joints of patients with Lyme arthritis. We hypothesized that MRP8/14 has a protective effect during B. burgdorferi infection. To determine the role of MRP8/14 in the immune response to B. burgdorferi, we studied the course of B. burgdorferi infection in wildtype (wt) and mrp14^?/? mice. In addition, we studied the response of leukocytes from mice lacking MRP8/14 to B. burgdorferi ex vivo. We demonstrated similar levels of B. burgdorferi dissemination, cytokine and immunoglobulin production in infected wt and mrp14^?/? mice after 21 days. Neutrophils and monocytes lacking MRP8/14 were undiminished in their ability to become activated or phagocytose B. burgdorferi. In conclusion, we did not find a central role of MRP8/14 in the immune response against B. burgdorferi. As the levels of MRP8/14 in the serum of infected mice were low, we speculate that MRP8/14 is not released in levels great enough to influence the course of B. burgdorferi infection.