Características demográficas y clínicas de los pacientes con enfermedad coronaria estable: resultados del registro CLARIFY en España

Introduction and objectives

Coronary artery disease is associated with high morbidity and mortality. The objective of the CLARIFY registry is to study the treatment of outpatients with coronary artery disease in the setting of daily clinical practice.

Methods

The CLARIFY registry is a prospective registry conducted in 41 countries that included outpatients with stable coronary artery disease attending primary care or specialist units between October 2009 and June 2010. The present study describes the baseline characteristics of the Spanish cohort compared with the western European cohorts included in the registry.

Results

A total of 33 248 patients were included: 14 726 in western Europe and 2257 in Spain (selected by 192 cardiologists). The majority of the participants in Spain were men (81%) with a mean age of 65 years. There was a higher frequency of diabetes (34% vs 25%; P < .0001), coronary artery disease family history (19% vs 31%; P < .0001), myocardial infarction (64% vs 60%; P < .0001), and stroke (5% vs 3%; P = .0007) in the Spanish cohort than in the western European cohorts. The most common treatments in the Spanish sample were lipid-lowering drugs (96%), acetylsalicylic acid (89%), and beta-blockers (74%).

Conclusions

Patients in the Spanish cohort are similar to those in the western European cohorts and seem to be representative of the Spanish population with coronary artery disease. Therefore, they form a suitable basis for the study of prognostic factors at 5-year follow-up.Full English text available from: www.revespcardiol.org/en     

El polimorfismo de un solo nucleótido PLAU P141L se asocia con el grado de circulación colateral en pacientes con enfermedad arterial coronaria

Introduction and objectives

Urokinase-type plasminogen activator, which is encoded by the PLAU gene, plays a prominent role during collateral arterial growth. We investigated whether the PLAU P141L (C > T) polymorphism, which causes a mutation in the kringle domain of the protein, is associated with coronary collateral circulation in a cohort of 676 patients with coronary artery disease.

Methods

The polymorphism was genotyped in blood samples using a TaqMan-based genotyping assay, and collateral circulation was assessed by the Rentrop method. Multivariate logistic regression models adjusted by clinically relevant variables to estimate odds ratios were used to examine associations of PLAU P141L allelic variants and genotypes with collateral circulation.

Results

Patients with poor collateral circulation (Rentrop 0-1; n = 547) showed a higher frequency of the TT genotype than those with good collateral circulation (Rentrop 2-3; n = 129; P = .020). The T allele variant was also more common in patients with poor collateral circulation (P = .006). The odds ratio of having poorly developed collaterals in patients bearing the T allele (adjusted for clinically relevant variables) was statistically significant under the dominant model (odds ratio =1.83 [95% confidence interval, 1.16-2.90]; P = .010) and the additive model (odds ratio =1.73 [95% confidence interval, 1.14-2.62]; P = .009).

Conclusions

An association was found between coronary collateral circulation and the PLAU P141L polymorphism. Patients with the 141L variant are at greater risk of developing poor coronary collateral circulation.Full English text available from: www.revespcardiol.org/en     

复方小柴胡汤对荷瘤小鼠NK细胞功能的影响

目的 探讨复方小柴胡汤(XCHT)对EAC荷瘤小鼠的免疫功能的影响.方法 用3种不同浓度的复方小柴胡汤对EAC荷瘤小鼠灌胃10 d,观察其肿瘤生长情况以及用乳酸脱氢酶释放法检测NK细胞的活性.结果 高、中和低浓度组NK细胞活性分别为(44.21±3.10)%,(51.09±4.94)%和(37.30±2.02)%,与空白对照组(31.26±2.79)%比较,NK细胞活性升高(P＜0.05),而阴性对照组(26.90±1.84)%NK细胞活性显著降低(P＜0.05);高、中和低浓度组的肿瘤质量为(300.6±48.9)mg,(226.5±36.4)mg和(445.9±60.2)mg,与阴性对照组(661.5±102.8)mg比较,均能抑制肿瘤的生长(P＜0.05),其中以中浓度组效果最为明显.结论 经过复方小柴胡汤灌胃的EAC荷瘤小鼠NK细胞活性均升高,3种不同浓度的复方小柴胡汤均使肿瘤生长减慢.     

腹水膏穴位贴敷对小鼠艾氏腹水癌的疗效影响

观察腹水膏穴位贴敷对小鼠艾氏腹水癌的疗效 ,并从细胞因子角度探讨其治疗机理。采用艾氏腹水癌瘤株用NIH小鼠接种 ,随机分正常空白对照组 (正空组 )、模型对照组 (模对组 )、局部贴敷组 (局贴组 )、穴位贴敷组 (穴贴组 ) 4组进行观察研究。结果 ,与模对组相比 ,腹水膏局贴或穴贴均可显著延长荷瘤小鼠生存期 (P <0 0 5 ,P <0 0 1) ,显著抑制恶性腹水增长速度 (P <0 0 5 ,P <0 0 1) ,穴位贴敷优于局部贴敷 (P <0 0 5 ) ;腹水膏可下调外周血sIL 2R水平 (P <0 0 5 ) ,显著提高外周血TNF杀伤活性 (P <0 0 0 1)。艾氏腹水癌小鼠存在细胞因子网络的调节失衡 ,腹水膏治疗艾氏腹水癌疗效确切 ,其机理可能为下调外周血sIL 2R水平 ,提高外周血TNF杀伤活性 ,促进细胞免疫功能。     

Mechanism of inhibition of DNA synthesis in Ehrlich ascites tumour cells by diazoacetyl glycine-amide

Treatment of Ehrlich ascites carcinoma bearing mice with DGA, the amide of diazoacetyl-glycine, leads to an inhibition of labelled thymidine incorporation into DNA of the tumour cells. This inhibition is not due to impairment of the nucleoside transport into the cell or to a modification in the activity of thymidine kinase. A possible explanation of the DGA effects resides in its partial inhibition of DNA polymerase and in its ability to alter the template activity of native DNA.     

Receptors for sheep erythrocytes (E) and erythrocyte-antibody-complement complexes (EAC) on the lymphoblasts of childhood acute lymphoblastic leukemia

Two cell-surface markers, rosette formation with sheep erythrocytes (E-rosette) as a T-cell marker and rosette formation with bovine erythrocyte-antibody-complement complex (EAC-rosette) as a B-cell marker were determined on peripheral blood lymphocytes and lymphoblasts from normal and 89 children with acute lymphoblastic leukemia (ALL). In the majority of the patients (12/15 untreated patients and 6/11 patients in relapse), lymphoblasts exhibited neither E- nor EAC-rosette formation. Lymphoblasts from one untreated patient with mediastinal mass displayed E-(50%) and EAC-rosette formation (15%). In 3 of 11 patients in relapse, lymphoblasts displayed an increase in EAC-rosette formation with progressive disease. In the remaining patients with active disease, a small and variable proportion of lymphoblasts expressed E and/or EAC-rosette formation. In 63 patients in remission, percentages of E- and/or EAC-rosette were similar (p > 0.05) to those of control. The results indicate a wide heterogeneity with respect to expression of lymphocyte membrane markers in lymphoblasts and in normal lymphocytes in patients with active ALL.     

Nitric oxide and acid induce double-strand DNA breaks in Barrett's esophagus carcinogenesis via distinct mechanisms

BACKGROUND & AIMS: The luminal microenvironment including acid and nitric oxide (NO) has been implicated in Barrett's esophagus carcinogenesis. We investigated the ability of acid and NO to induce DNA damage in esophageal cells. METHODS: Transformed and primary Barrett's esophagus and adenocarcinoma cells were exposed to either acid, (pH 3.5), +/- antioxidant or NO from a donor or generated by acidification of nitrite in the presence of ascorbate +/- NO scavenger. Phosphorylation of histone H2AX and the neutral comet assay were used to detect DNA double-strand breaks (DSBs). Intracellular levels of reactive oxygen species and NO were detected with fluorescent dyes. Mitochondrial viability was measured with a rhodamine dye. Long-term survival was assessed by clonogenic assay. RESULTS: Exposure to acid (pH 3.5) for > or =15 minutes induced DSBs in all cell lines (P < .05). There was a concomitant increase in intracellular reactive oxygen species in the absence of mitochondrial damage, and pretreatment with antioxidants inhibited DNA damage. Exposure to physiologic concentrations of NO produced from the NO donor or acidification of salivary nitrite induced DSBs in a dose- (>25 micromol/L) and cell-dependent manner (adenocarcinoma >Barrett's esophagus, P < .05). This occurred preferentially in S-phase cells consistent with stalled replication forks and was blocked with a NO scavenger. NO also induced DSBs in primary Barrett's esophagus cells treated ex vivo. Cells were able to survive when exposed to acid and NO. CONCLUSIONS: Both acid and NO have the potential to generate DSBs in the esophagus and via distinct mechanisms.     

顺铂与阿霉素合用的抗瘤活性与剂量的关系

以体外培养瘤细胞集落形成率、荷瘤小鼠生命延长率(ILS)和小鼠实体瘤的抑瘤率作为药效的评价指标,观察顺铂(DDP)与阿霉素(ADM)合用的剂量效应关系。小剂量DDP与ADM的联用时相加作用明显。一种药已达有效量再与另一药小剂量合用其效应与单药足量的效应无显著差异;若两药有效量联合,虽能提高ILS,但表现出毒性增强。