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Introduction Fibroadenomas of the breast present as two phenotypic variants. The usual variety is 5 cm or less in diameter and there is another large variant called giant fibroadenoma which is greater than 5 cm in diameter. Despite of its large size, it is not malignant. The aim of our study is to determine whether this large variant is different from the usual fibroadenoma in terms of its biological pathways and biomarkers. Methods mRNA was extracted from 44 fibroadenomas and 36 giant fibroadenomas, and transcriptomic profiling was performed to identify up- and down-regulated genes in the giant fibroadenomas as compared to the fibroadenomas. Results A total of 40 genes were significantly up-regulated and 18 genes were significantly down-regulated in the giant fibroadenomas as compared to the fibroadenomas of the breast. The top 5 up-regulated genes were FN1, IL3, CDC6, FGF8 and BMP8A. The top 5 down-regulated genes were TNR, CDKN2A, COL5A1, THBS4 and BMPR1B. The differentially expressed genes (DEGs) were found to be associated with 5 major canonical pathways involved in cell growth (PI3K-AKT, cell cycle regulation, WNT, and RAS signalling) and immune response (JAK-STAT signalling). Further analyses using 3 supervised learning algorithms identified an 8-gene signature (FN1, CDC6, IL23A, CCNA1, MCM4, FLT1, FGF22 and COL5A1) that could distinguish giant fibroadenomas from fibroadenomas with high predictive accuracy. Conclusion Our findings demonstrated that the giant fibroadenomas are biologically distinct to fibroadenomas of the breast with overexpression of genes involved in the regulation of cell growth and immune response.

The marine Synechococcus is a major primary producer in the global oceans. It is phylogenetically highly diverse, and its major phylogenetic lineages display clear spatial segregation among different marine environments. Here, we showed that the composition of the associated bacterial communities was related to the geographic origin of the different Synechococcus strains, and it was stable during long-term lab incubation. Of all the Synechococcus cultures investigated, the Rhodobacteraceae had a relatively high abundance and was the core bacterial family of the associated bacterial communities. In contrast, the Flavobacteriaceae were only abundant in the cultures collected from the South China Sea (which is warm and oligotrophic), whereas those of the Alteromonadaceae were abundant in the cultures from the coastal waters off Hong Kong and Xiamen. We also found that the Rhodobacteraceae had more ABC transporters and utilized a wider spectrum of carbon sources than did the Flavobacteriaceae and Alteromonadaceae. Moreover, the Alteromonadaceae had more transporters for importing phosphate and amino acids, but fewer transporters for importing oligosaccharides, polyol, and lipid, than the Flavobacteriaceae. Furthermore, metagenomic analysis demonstrated that bacteria involved in nitrate-ammonification prevailed in all the cultures. These results imply that networks formed by phytoplankton and heterotrophic bacteria might vary across habitats, and that different dominant bacterial groups play different roles in the phycosphere. This study provides new insight into the unique interactive and interdependent bond between phytoplankton and their associated microbiome, which may enhance our understanding of carbon and nutrient cycling in marine environments.

We sought to determine the clinical significance of aspirin resistance measured by a point-of-care assay in stable patients with coronary artery disease (CAD).We used the VerifyNow Aspirin (Accumetrics Inc, San Diego, Calif) to determine aspirin responsiveness of 468 stable CAD patients on aspirin 80 to 325 mg daily foror =4 weeks. Aspirin resistance was defined as an Aspirin Reaction Unitor =550. The primary outcome was the composite of cardiovascular death, myocardial infarction (MI), unstable angina requiring hospitalization, stroke, and transient ischemic attack.Aspirin resistance was noted in 128 (27.4%) patients. After a mean follow-up of 379+/-200 days, patients with aspirin resistance were at increased risk of the composite outcome compared to patients who were aspirin-sensitive (15.6% vs 5.3%, hazard ratio [HR] 3.12, 95% confidence intervals [CI], 1.65-5.91, P.001). Cox proportional hazard regression modeling identified aspirin resistance, diabetes, prior MI, and a low hemoglobin to be independently associated with major adverse long-term outcomes (HR for aspirin resistance 2.46, 95% CI, 1.27-4.76, P = .007).Aspirin resistance, defined by an aggregation-based rapid platelet function assay, is associated with an increased risk of adverse clinical outcomes in stable patients with CAD.

OBJECTIVE Current arterial transfer functions have low capability in predicting aortic augmentation index (AIx) from radial pulse contour (RPC), because of the difficulty in accurately identifying the merging point (inflection point) in the derived aortic pulse contour (APC). We hypothesize that the formation time between each characteristic wave in APC is about one-third of ejection duration (ED/3). We sought to assess the accuracy of ED/3 in identifying the merging point in APC as compared to the conventional differential method. In addition, we sought to derive the AIx from RPC based on an arterial transfer function and the ED/3 method. METHODS APC and RPC sequences were measured digitally and simultaneously in 60 subjects (37 males; aged 60 +/- 10 years). An ensemble-averaged RPC-to-APC transfer function was determined from 30 randomly selected subjects and was used to derive APC sequences in the 30 additional subjects. The accuracy of AIx predicted from RPC was determined. RESULTS In patients with a clearly identifiable merging point in APC, the ED/3 method identified the merging point of measured APC within 1.97 +/- 0.60 ms of that identified by the conventional differential method, with identical AIx. The AIx and merging point of derived APC using the ED/3 method were also within 0.22 +/- 1.01% and 1.81 +/- 1.64 ms, respectively, of those of the measured APC using the conventional differential method. The accuracy of the predicted AIx was independent of age, sex, body-mass index and presence of hypertension. CONCLUSION In a quiet resting state, the ED/3 is an alternative method for identifying the merging point in APC. In conjunction with transfer-function technique, AIx can be derived accurately from RPC.

Previous studies have shown that more complete platelet inhibition improves the coronary flow reserve (CFR), a measure of microvascular integrity, in patients undergoing percutaneous coronary intervention (PCI). We hypothesized that patients with aspirin resistance would have impaired CFR after elective PCI. We used VerifyNow Aspirin to determine the response to aspirin in 117 consecutive patients who underwent elective single-lesion PCI. The assay results are expressed quantitatively in Aspirin Reaction Units based on the degree of platelet aggregation. All patients received a 300-mg loading dose of clopidogrel >12 hours before and a 75-mg maintenance dose the morning of PCI. CFR was estimated using the Thrombolysis In Myocardial Infarction frame count method. Of the 117 patients, 22 (18.8%) were aspirin resistant. The clinical, angiographic, and procedural characteristics of the aspirin-sensitive and -resistant patients were balanced. All patients underwent successful PCI with

The FilterWire EX is one of the filter protection devices developed as alternatives to balloon occlusion system for percutaneous coronary intervention. Its use has been recommended in vessels between 3.5 and 5.5 mm in diameter and no data are available on its use in smaller vessels. We evaluated the safety and feasibility of using FilterWire EX in native coronary arteries smaller than 3.5 mm. We successfully deployed and retrieved the FilterWire EX in 49 coronary arteries with a mean vessel diameter of 2.62 +/- 0.45 mm at device deployment. Reversible vasospasm was observed in 24 (50%) vessels, coronary flow was temporarily reduced in 22 (44.9%), and distal embolization was noted in 2 (4%). There was no vessel dissection induced by the device. These data suggest that it is safe and feasible to use the FilterWire EX in small coronary arteries.

Background: Most published studies on the use of lipid-lowering agents to treat hypercholesterolemia have focused on Western populations, with few data on Asian populations. Objective: The Simvastatin Treats Asians to Target (STATT) study used a titrate-to-goal protocol to evaluate the efficacy and tolerability of simvastatin 20 to 80 mg/d in the treatment of Asian patients with coronary heart disease. Methods: This was a multicenter, open-label, uncontrolled, 14-week study in patients with coronary heart disease and serum low-density lipoprotein cholesterol (LDL-C) levels of 115–180 mg/dL and triglyceride levels of ≤400 mg/dL. The dose of simvastatin was titrated from 20 to 80 mg/d to achieve the National Cholesterol Education Program (NCEP) LDL-C target of ≤100 mg/dL. The primary efficacy measure was the percentage of patients achieving the NCEP target. Among secondary measures were the percentage of patients achieving European Society of Cardiology/European Atherosclerosis Society/European Society of Hypertension target LDL-C levels of ≤115 mg/dL and the percentage change from baseline in lipid parameters. Tolerability was assessed in terms of the overall incidence of adverse experiences and the incidences of the most commonly reported adverse experiences. Results: The intent-to-treat analysis included 133 Asian patients (93 men, 40 women; mean age, 59.5 years), of whom 125 completed 14 weeks of therapy. Their mean blood pressure was 130.2/79.4 mm Hg. Overall, 104 (78.2%) patients treated with simvastatin achieved LDL-C levels ≤100 mg/dL at week 14, and 125 (94.0%) achieved this target at some point during the study. Similarly, 122 (91.7%) patients achieved an LDL-C level ≤115 mg/dL at week 14, and 130 (97.7%) achieved this target at some point during the study. Treatment with simvastatin had favorable effects on the lipid profile, producing significant percentage changes from baseline in all parameters ( P Conclusions: Simvastatin was effective and well tolerated at doses of 20, 40, and 80 mg/d in Asian patients with coronary heart disease. Titration enabled the majority to achieve target LDL-C levels of ≤100 mg/dL.

The Safe-Cross wire system, which has optical coherence reflectometry technology for navigating and radiofrequency energy provided at its tip for crossing chronic total occlusions (CTOs), provides a promising means to treat hard, organized CTOs. Using this system, we report on a 60% success rate in patients who had long-standing coronary CTOs that had ≥1 failed attempt using conventional percutaneous coronary intervention.

Coronary artery disease remains the leading cause of death in developing countries. In the United States, up to 12 million Americans have a history of myocardial infarction, angina pectoris, or both (1). Although recent advances in medical treatment and interventional procedures have reduced the mortality in patients with coronary artery disease (2), the number of patients with refractory myocardial ischemia and congestive heart failure is rapidly increasing. In a significant proportion of these patients, percutaneous coronary intervention or surgical bypass revascularization is either not feasible or incomplete as a result of patients’ comorbidity, total occlusion, or poor distal vessels. After a myocardial infarction, some cardiomyocytes are lost and others hibernate because of insufficient myocardial perfusion. Therefore, therapeutic approaches aimed at promoting blood vessel formation (angiogenesis) and growing new heart muscle fibers (myocardial regeneration) are attractive alternatives. Accumulating evidence suggests that bone marrow cells have the potential of contributing to tissue revascularization and cardiac regeneration after myocardial injury. This chapter summarizes the current status of bone marrow cell transplantation for myocardial regeneration and therapeutic angiogenesis.

Aim: The use of low-dose aspirin to prevent cardiovascular disease events is well established. However, the incidence and predictors of upper gastrointestinal bleeding (UGIB) with its use are unknown. We studied prospectively the incidence and outcome of peptic ulceration in low-dose aspirin users. Methods: A total of 991 patients with coronary artery disease (CAD) on low-dose aspirin were prospectively followed-up for two years for the occurrence and clinical features of first hospitalized episode of UGIB. Results: UGIB had a bimodal presentation with 45% occurring within four months of aspirin initiation and had an overall prevalence of 1.5% per year. There was no UGIB-related death. Hypertension (OR = 4.6, 95%CI 1.5 - 14.7, P = 0.009), history of peptic ulceration (OR = 3.1, 95%CI 1.1 - 9.0, P = 0.039), tertiary education (OR = 3.08, 95%CI 1.1 - 9.0, P = 0.039) and higher lean body mass (P = 0.016) were independent factors associated with UGIB. Use of nitrate did not reduce UGIB. Conclusion: The incidence of UGIB in patients with CAD on long-term low-dose aspirin is low, but is accompanied with significant morbidity. With prolonged use of aspirin, UGIB continues to be a problem for those with risk factors and especially in patients with a history of peptic ulcers, in which UGIB tends to occur early after aspirin therapy. © 2006 The WJG Press. All rights reserved., published_or_final_version

Coronary stenting is associated with a high incidence of restenosis in patients with diabetes mellitus. Recent data suggest that diabetic patients treated with abciximab have a lower rate of target vessel revascularization (TVR). We sought to investigate whether abciximab can reduce in-stent restenosis after coronary stenting in diabetic patients.In this prospective double-blind trial, we randomly assigned 254 patients with type 2 diabetes mellitus undergoing nonurgent coronary stenting to receive abciximab with an initial heparin bolus of 50 U/kg (n = 128) or placebo with an initial heparin bolus of 70 U/kg (n = 126). All patients received aspirin and clopidogrel before the procedure. The primary endpoint was angiographic restenosis by quantitative coronary angiography at 6 months. The secondary endpoint was death, myocardial infarction (MI), or target lesion revascularization (TLR) at 6 months.The clinical, angiographic, and procedural characteristics were matched between the 2 groups. Angiographic follow-up was completed in 226 patients (90%). Angiographic restenosis occurred in 29.1% of the abciximab group, and 24% of the placebo group (p = 0.30). The rates of the secondary endpoint were similar between the 2 groups (23.4% in the abciximab group versus 22.2% in the placebo group; p = 0.88). TLR was performed on 36 (18.4%) lesions in 29 (23.4%) patients of the abciximab group, and 26 (13.6%) lesions in 23 (18.3%) patients of the placebo groups, respectively (p = 0.21 and 0.35, respectively).Abciximab does not reduce angiographic restenosis or TLR in type 2 diabetic patients undergoing nonurgent coronary stenting.

Patients with chronic renal failure, because of concomitant conventional cardiovascular and uremia-associated risk factors, are at risk of developing diffuse and accelerated atherosclerosis involving both the coronary and peripheral territories. We report an end-stage renal failure patient with a history of coronary artery bypass surgery who developed both angina and dizziness during hemodialysis via a left forearm arteriovenous fistula. Magnetic resonance imaging diagnosed the presence of significant subclavian artery stenosis. The patient then underwent successful percutaneous stenting of the left subclavian artery. His angina and dizziness symptoms resolved subsequently. Catheter Cardiovasc Interv 2004;62:244–248. © 2004 Wiley-Liss, Inc.

Subclavian artery lesion that is associated with low complication rate could be treated by percutaneous intervention effectively. However, the success of endovascular therapy for occlusive lesion may be limited by failure to cross with a guidewire. We describe the use of a system using optical coherence reflectometry for navigation and radiofrequency ablation to enable wire passage through subclavian artery occlusion that could not be crossed by conventional guidewires.

OBJECTIVES We sought to investigate the effect of aspirin resistance on the incidence of myonecrosis after non-urgent percutaneous coronary intervention (PCI) among patients pretreated with clopidogrel. BACKGROUND Oral antiplatelet therapy using aspirin and a thienopyridine is the standard of care for preventing thrombotic complications of PCI. The effect of aspirin resistance on the outcomes of patients undergoing PCI is unknown. METHODS We used the Ultegra Rapid Platelet Function Assay-ASA (Accumetrics Inc., San Diego, California) to determine aspirin responsiveness of 151 patients scheduled for non-urgent PCI. All patients received a 300-mg loading dose of clopidogrel >12 h before and a 75-mg maintenance dose in the morning of the PCI. The incidence of myonecrosis was measured by creatine kinase-myocardial band (CK-MB) and by troponin I (TnI) elevations after PCI. RESULTS A total of 29 (19.2%) patients were noted to be aspirin-resistant. There was a significantly higher incidence of female subjects in the aspirin-resistant versus aspirin-sensitive groups. The incidence of any CK-MB elevation was 51.7% in aspirin-resistant patients and 24.6% in aspirin-sensitive patients (p = 0.006). Elevation of TnI was observed in 65.5% of aspirin-resistant patients and 38.5% of aspirin-sensitive patients (p = 0.012). Multivariate analysis revealed aspirin resistance (odds ratio [OR] 2.9; 95% confidence interval [CI] 1.2 to 6.9; p = 0.015) and bifurcation lesion (OR 2.8; 95% CI 1.3 to 6.0; p = 0.007) to be independent predictors of CK-MB elevation after PCI. CONCLUSIONS Despite adequate pretreatment with clopidogrel, patients with aspirin resistance as measured by a point-of-care assay have an increased risk of myonecrosis following non-urgent PCI.

Chronic total occlusions remain a challenge to interventionalists due to failure of crossing or perforation by strong wires. We describe the use of a system using optical coherence reflectometry for navigation and radiofrequency ablation to enable wire passage through occlusions that could not be crossed by conventional guidewires.

This study assessed the pharmacokinetics, safety and efficacy of intravenous enoxaparin in patients undergoing percutaneous coronary intervention (PCI). Sixty consecutive patients [(age, 62 11 years; female, 16%; diabetes, 18%; hypertension, 53%; prior myocardial infarction (MI), 43%] undergoing PCI (stable angina, 89%; stent, 92%; two-vessel disease, 23%; B2/C lesions, 45%) were administered intravenous enoxaparin 1 mg/kg for procedural anticoagulation. Blood samples for anti-Xa level and activated partial thromboplastin time (aPTT) were assayed from the first 20 patients before and after enoxaparin administration at the following intervals: 5, 30, 60, 90, 120, 150, 180, 210, 240, 360 and 480 minutes. Activated clotting time was assessed 5 minutes after enoxaparin administration. Bleeding complications were classified according to Thrombolysis In Myocardial Infarction (TIMI) criteria. All patients were monitored for adverse clinical events at clinic visit 4 8 weeks after hospital discharge. No TIMI major or minor bleedings occurred during hospitalization for the PCI (median stay post-PCI = 1 day). One patient (2%) developed a non-Q wave MI after the PCI and before hospital discharge. There was no death or urgent revascularization up to clinical follow-up. The peak anti-Xa level was 1.30 0.18 IU/ml (range, 1.03 1.69 IU/ml). The minimum anti-Xa level was 0.55 IU/ml 4 hours after enoxaparin. Thus, the use of intravenous enoxaparin in patients undergoing PCI is associated with a low incidence of ischemic and bleeding complications. A stable therapeutic anticoagulant effect is provided without the need for monitoring within 4 hours of enoxaparin administration.

Synchronous biventricular pacing is a new nonpharmacological supplemental treatment of advanced heart failure associated with electromechanical conduction delay. However, the role of pacing on left ventricular remodeling is unknown. Eleven patients with New York Heart Association Class III to IV heart failure, a left ventricular ejection fraction or = 140 ms received a biventricular dual chamber pacemaker. Serial echocardiography, 6-minute hall walk, and Minnesota Living with Heart Failure quality-of-life (QOL) questionnaire were performed before and after up to 3 months of pacing. At 3 months there was a significant increase in fractional shortening (P < 0.001), ejection fraction (P < 0.001), and cardiac output (P < 0.05). The left ventricular end-diastolic volume (245 +/- 70 vs 185 +/- 37 mL, P < 0.05), end-systolic volume (209 +/- 69 vs 140 +/- 44 mL P < 0.05), and mitral regurgitation were reduced (P < 0.05), and diastolic filling time was lengthened (P < 0.05). There were also improvements in heart failure symptoms, an increase in 6-minute walk distance, and a decrease in QOL scores. Synchronous biventricular pacing for 3 months was associated with hemodynamic improvements, reversal of left ventricular remodeling, and increase in left ventricular systolic function, and a decrease in secondary mitral regurgitation.