Effect of polymorphism and type II diabetes on aspirin resistance in patients with unstable coronary artery disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Aspirin is widely used in the secondary prevention of coronary artery diseases, including myocardial infarction, stroke, and vascular related deaths. However, the antiplatelet effect of aspirin appears to be variable and aspirin resistance (AR) is currently still controversial for Chinese patients. The aim of this study was to describe the prevalence of AR, and identify possible risk factors associated with a lack of response to aspirin treatments in patients with unstable coronary artery disease.</p><p><b>METHODS</b>Platelet function tests with arachidonic acid (ARA) and urinary 11-dehydro-thromboxane B2 (11-DH-TXB2) concentrations were performed in 262 patients with unstable coronary artery disease who had not been taking aspirin before admission. ARA induced platelet aggregation and 11-DH-TXB2 were detected to evaluate the functional and biochemical responses to aspirin before and on days 1, 4, and 10 after aspirin administration. Six-month follow-up was completed in patients who developed AR to evaluate the effect of aspirin in a long-term treatment. GP1Bα (C1018T), Pl (A1/A2), P2Y1 (A1622G), TBXA2R (T924C) were also detected to evaluate the influence of genetic variant on aspirin responsiveness.</p><p><b>RESULTS</b>A total of 8.8% of patients were indentified as AR at the first day after aspirin treatment. The level of urine 11-DH-TXB2 in the AR group was higher compared to non-AR group (P < 0.05). There was no relationship between ARA induced platelet aggregation and urinary 11-DH-TXB2 levels (r = 0.038, P = 0.412). The results of DNA sequencing showed that TBXA2R-924TT homozygotes had a significantly high rate of AR. Logistic regression demonstrated that diabetes was an independent risk factor of AR.</p><p><b>CONCLUSIONS</b>In the beginning period of administration, aspirin was not a sufficient factor that inhibits platelet aggregation. TBXA2R-924T allele was involved in AR. Diabetes was an independent risk factor of AR.</p>

Early and long-term results of combined cardiac surgery and neoplastic resection in patients with concomitant severe heart disease and neoplasms / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It is a surgical dilemma when patients present with both severe heart disease and neoplasms. The best surgical treatment remains controversial. This study aimed to analyze the early and long-term results of simultaneous surgical treatment of severe heart disease and neoplasms.</p><p><b>METHODS</b>We reviewed the clinical records of 15 patients who underwent simultaneous neoplastic resection and cardiac surgery between September 2006 and January 2011. There were 5 male and 10 female patients. The mean age was (59.2 ± 12.5) years and the mean left ventricular ejection fraction was (57.4 ± 11.0)%. All patients were followed up completely for a period of 12 to 51 months (mean, (33.1 ± 11.2) months).</p><p><b>RESULTS</b>Fifteen patients underwent simultaneous cardiac surgery and neoplastic resection. Cardiac procedures consisted of off pump coronary artery bypass grafting (n = 7), aortic valve replacement (n = 3), mitral valve replacement (n = 3), mitral valve replacement with coronary artery bypass grafting (n = 1) and left atrial myxoma resection (n = 1). Neoplastic resection consisted of lung cancer resection (n = 5), colonic cancer resection (n = 3), gallbladder resection (n = 1), colonic cancer resection with gallbladder resection (n = 1), hysterectomy (n = 2), hysterectomy with bilateral salpingo-oophorectomy (n = 2) and left ovariectomy (n = 1). Pathological examination confirmed malignant disease in 10 patients and benign disease in 5 patients. There were no perioperative myocardial infarctions, stroke, pericardial tamponade, renal failure or hospital deaths. The most frequent complications were atrial fibrillation (33.3%), pneumonia (26.7%), low cardiac output syndrome (6.7%) and delayed healing of surgical wounds (6.7%). There was 1 late death 42 months after surgery for recurrent malignant disease. At 1 and 3 years, survival rates were 100% (Kaplan-Meier method).</p><p><b>CONCLUSIONS</b>Simultaneous cardiac surgery and neoplastic resection was not associated with increased early or late morbidity or mortality. Cardiopulmonary bypass does not appear to adversely affect survival in patients with malignant disease. The long-term survival was determined by tumor stage.</p>

Association of polymorphisms of cytochrome P450 2C9 exon 4 and -65G>C with warfarin sensitivity / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association of the polymorphisms of cytochrome P450 2C9 (CYP2C9) exon 4 608T/G, 561A/C, 537A/C and 527A/C, and -65G/C with warfarin sensitivity.</p><p><b>METHODS</b>A total of 102 patients under warfarin anticoagulant therapy were selected. During follow-up, warfarin dosage and associated Prothrombin Time-International Normalized Ratio (P-INR) values were recorded. Simultaneous monitoring of incidence of bleeding and thrombosis adverse effect was recommended. Genetic polymorphisms of the above mentioned loci were identified by polymerase chain reaction and DNA sequencing.</p><p><b>RESULTS</b>The average age of the 102 patients was (62.1+/-10.5) years. The body mass index (BMI) was (24.7+/-3.8) kg/m2. Mean daily warfarin requirement was from 1.250 to 5.077 mg/day when therapeutic PT-INR (1.5-2.5) was maintained. DNA sequencing showed no polymorphisms of 608T/G, 561A/C, 537A/C, 527A/C in CYP2C9 exon 4. Warfarin daily dosage in CYP2C9 exon 4 -65C carriers was 3.106+/-0.619 mg/d, while it was (2.555+/-0.708) mg/d in individuals with wild-type -65G (P=0.020). Receiver operating characteristic (ROC) analysis showed that warfarin daily dosage of more than 2.5 mg/d can be used to predict the CYP2C9 exon 4 -65GC genotype (AUC: 0.770, P=0.005, 95%CI:0.626-0.915). Logistic regression indicated that BMI was an independent factor of bleeding during anti-coagulation therapy (OR=0.794, 95%CI: 0.651-0.970, P=0.024).</p><p><b>CONCLUSION</b>The Chinese population are, generally, warfarin-sensitive. Exon 4 of the CYP2C9 gene is highly conserved in this population. The warfarin maintenance dosage in CYP2C9 exon 4 -65CG carriers was significantly higher than those with wild-type -65GG. The clinical significance needs further investigation with more large-scale, multi-center trials.</p>

Association of serotonin transporter gene linked polymorphic region polymorphism with early onset myocardial infarction and platelet membrane glycoprotein I b / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association of serotonin transporter gene linked polymorphic region (5-HTTLPR) insertion/deletion polymorphism with early onset myocardial infarction(MI) and platelet membrane glycoprotein I b(GP I b) in Northern Han population of China.</p><p><b>METHODS</b>A total of 150 patients with early onset MI and 150 age- and sex-matched controls with negative coronary arteriography were genotyped for the 5-HTTLPR polymorphism by using a polymerase chain reaction-based technique. The percentage of positive platelet membrane GP I b and the average fluorescence intensity were quantified by flow cytometry.</p><p><b>RESULTS</b>The genotype frequencies of LL, LS and SS in the 5-HTTLPR were 32%, 47% and 21% in the MI patients, 17%, 43% and 39% in the controls respectively(P<0.01). The L allele frequency in the MI patients was significantly higher than that of the control group (56% vs 39%, P<0.01). The percentage of positive platelet membrane GP I b and the fluorescence intensity in subjects with LL homozygote were markedly lower than that of LS and SS genotypes in the MI and control groups (all P<0.01). Multivariate logistic regression analysis showed that the 5-HTTLPR LL genotype was independently related to the occurrence of early onset MI(OR was 1.961, P was 0.037).</p><p><b>CONCLUSION</b>The LL genotype of the 5-HTTLPR might be associated with the susceptibility to developing early MI in Northern Han population of China. The platelet activation is increased in individuals of LL genotype.</p>

Effect of pericardial suction blood re-transfusion in off-pump coronary artery bypass grafting on inflammatory cytokines, myocardial injury and pulmonary function / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of pericardial suction blood re-transfusion in off-pump coronary artery bypass grafting (CABG) on inflammatory cytokines, myocardial injury and lung function.</p><p><b>METHODS</b>31 patients of off-pump CABG were divided into two study groups (OPCABG1 group and OPCABG2 group) according to the amount of pericardial suction blood re-transfusion beyond or less than 600 ml. 13 patients of on-pump CABG were control group. Serum samples from vein were collected for measurement of IL-6, IL-8, IL-10 and TNF-alpha pre-operation and 1, 4, 24, 48 hours post-operation respectively. The results of CK-MB, TnI, AaDO2 and PaO2/FiO2 were recorded.</p><p><b>RESULTS</b>Patients of the three groups had no significant difference in terms of gender, age, bodyweight, history of hypertension and cardiac infarction and diabetes, EF and left ventricular end diastolic of pre-operation, the amount of bypass graft and shed blood. Of the three groups, IL-6, IL-8 and IL-10 reached peak level one hour after the operation, and dropped to the pre-operation level 72 hours after the operation. One hour after the operation, the level of IL-6 and IL-8 in OPCABG1 group was higher than in OPCABG2 group (P < 0.05) and about the same in CABG group (P > 0.05). Four hours after the operation, the level of CK-MB in OPCABG1 group was lower than that of CABG group (P < 0.05) and about the same in OPCABG2 group (P >0.05). 4 and 24 hours after the operation, the level of TnI in OPCABG1 group was lower than that of CABG group (P < 0.05) and about the same in OPCABG2 group (P > 0.05). Among the three groups, there was no significant difference in AaDO2 and PaO2/FiO2.</p><p><b>CONCLUSIONS</b>Re-transfusion of large amount of pericardial suction blood can increase serum level of IL-6, IL-8, but it can not cause myocardial injury and affect the gas exchange function of lung significantly.</p>