Aspirin and clopidogrel drug response in patients undergoing percutaneous coronary intervention: the role of dual drug resistance.

We evaluated the response to clopidogrel among aspirin-resistant versus aspirin-sensitive patients undergoing elective coronary stenting. Patients (n = 150) treated with aspirin but not clopidogrel had blood samples drawn at baseline and 24 h after clopidogrel loading. Depending on the definition used, 9% to 15% were resistant to aspirin and 24% to clopidogrel. About half of the aspirin-resistant patients were also resistant to clopidogrel. As a group, aspirin-resistant patients had lower response to clopidogrel (assessed by platelet aggregation and activation markers) than aspirin-sensitive patients. Both aspirin- and clopidogrel-resistant patients had higher incidence of creatine kinase-MB elevation than the respective sensitive patients. OBJECTIVES: We sought to evaluate the response to clopidogrel among aspirin-resistant versus aspirin-sensitive patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: Wide variability has been reported in response to aspirin and clopidogrel. There are limited data on the simultaneous responses to both drugs. METHODS: Elective PCI patients (n = 150) who received aspirin for > or = 1 week but not clopidogrel were included. All patients received bivalirudin during PCI. Blood samples were drawn at baseline and 20 to 24 h after a 300-mg clopidogrel dose. Aspirin resistance was defined by > or = 2 of 3 criteria: rapid platelet function analyzer-ASA score > or = 550, 5 micromol/l adenosine diphosphate (ADP)-induced aggregation > or = 70%, and 0.5 mg/ml arachidonic acid-induced aggregation > or = 20%. Clopidogrel resistance was defined as baseline minus post-treatment aggregation < or = 10% in response to 5 and 20 micromol/l ADP. RESULTS: Nineteen (12.7%) patients were resistant to aspirin and 36 (24%) to clopidogrel. Nine (47.4%) of the aspirin-resistant patients were also clopidogrel resistant. Aspirin-resistant patients were more likely to be women and have diabetes than were aspirin-sensitive patients. They also had lower response to clopidogrel, assessed by platelet aggregation and activation markers (flow cytometry-determined PAC-1 binding and P-selectin expression). Elevation of creatine kinase-myocardial band after stenting occurred more frequently in aspirin-resistant versus aspirin-sensitive patients (38.9% vs. 18.3%; p = 0.04) and in clopidogrel-resistant versus clopidogrel-sensitive patients (32.4% vs. 17.3%; p = 0.06). CONCLUSIONS: Aspirin-resistant patients as a group have reduced response to clopidogrel. Furthermore, we have identified a unique group of dual drug-resistant patients who may be at increased risk for thrombotic complications after PCI.     

Circulating endothelial progenitor cells and coronary collaterals in patients with non-ST segment elevation myocardial infarction

BACKGROUND: Endothelial progenitor cells (EPCs) are bone marrow-derived cells that are augmented in response to ischemia and incorporated into neovascularization sites. We sought to determine whether circulating EPCs are related to collateral formation following non-ST segment elevation myocardial infarction (NSTEMI). METHODS: Twenty patients who underwent percutaneous coronary intervention (PCI) within a week of NSTEMI were divided into two groups: patients without collaterals (coll-, n=10) and patients with Rentrop grade 3--4 collaterals (coll+, n=10). Blood samples were drawn before PCI and 24+/- 2 h after PCI. EPC colonies were grown from peripheral blood mononuclear cells, characterized, and counted. Using flow cytometry the percentage of cells co expressing vascular endothelial growth factor receptor-2 and CD 133 was determined. RESULTS: The coll+ group had higher degree of culprit vessel stenosis and lower initial thrombolysis in myocardial infarction flow grade. The relative number of EPCs before PCI was significantly higher in the coll+ group than in the coll- group (1.49 +/- 0.9% vs. 0.77+/- 0.4%, p= 0.045). There were no significant intergroup differences in the number of EPC colony-forming cells. The number of EPC colonies increased in the coll- group after PCI (9.5 +/- 4.8 to 14.0 +/- 5.9/10(6) cells, p=0.01). CONCLUSIONS: This study supports an association between circulating EPC levels and collateral formation in patients with an NSTEMI.     

O等位基因引起ABO基因型与表现型定型差异

保证输血时血清学方面的安全,首要的是对受血者与献血者ABO血型定型,血清学检查通常分两个步骤.正定型通常使用鼠源单克隆抗体检测红细胞表面是否存在A或B抗原.互补的实验即反定型,利用当红细胞上缺乏A或B抗原时,人群可天然产生相对应的抗体的原理,检测血清中是否存在抗-A或者抗-B抗体.确定了受血者红细胞表面的ABO抗原以及血浆中的抗体,便能确定血型,为其提供相合的血液.     

The echo-transponder electrode catheter: a new method for mapping the left ventricle

The ability to locate catheter position in the left ventricle with respect to endocardial landmarks might enhance the accuracy of ventricular tachycardia mapping. An echo-transponder system (Telectronics, Inc.) was compared with biplane fluoroscopy for left ventricular endocardial mapping. A 6F electrode catheter was modified with the addition of a piezoelectric crystal 5 mm from the tip. This crystal was connected to a transponder that received and transmitted ultrasound, resulting in a discrete artifact on the two-dimensional echocardiographic image corresponding to the position of the catheter tip. Catheters were introduced percutaneously into the left ventricle of nine anesthetized dogs. Two-dimensional echo-transponder and biplane fluoroscopic images were recorded on videotape with the catheter at multiple endocardial sites. Catheter location was marked by delivering radiofrequency current to the distal electrode, creating a small endocardial lesion. Catheter location by echo-transponder and by fluoroscopy were compared with lesion location without knowledge of other data. Location by echo-transponder was 8.7 +/- 5.1 mm from the center of the radiofrequency lesion versus 14 + 7.8 mm by fluoroscopy (n = 15, p = 0.023). Echo-transponder localization is more precise than is biplane fluoroscopy and may enhance the accuracy of left ventricular electrophysiologic mapping.     

Resectable Well-Differentiated versus Dedifferentiated Liposarcomas: Two Different Diseases Possibly Requiring Different Treatment Approaches

Background Division of retroperitoneal liposarcoma (RPLS) into well-differentiated (WD) and dedifferentiated (DD) subtypes is established; however, WD and DD are usually treated similarly. We hypothesized that WD and DD have distinct biological behaviors mandating different treatments. Methods A prospective sarcoma database identified all primary/recurrent RPLS treated between 1996 and 2007: 77 DD (52%) and 58 WD (39.2%) patients were analyzed for recurrence rate, recurrence free survival (RFS), and overall survival (OS). Results At presentation, WD were mostly primary whereas DD were mostly recurrent (75.9% versus 58.4%; p = 0.04). A significant proportion of DD (37.7%) received chemotherapy compared to WD (1.7%; p < 0.0001). Multivisceral resection was more common in DD versus WD (45.5% versus 31%; p = 0.01). Gross total resection rates were equivalent (WD: 86.2%; DD: 85.7%). Overall and local recurrence were higher in DD versus WD (82.2% versus 50% and 71.2% versus 46.3%; p < 0.0001). Only 3.7% WD recurred as high grade metastatic disease. Median time to recurrence was 55.5 months in WD versus 13.5 months in DD (p < 0.0001). RFS and OS (1, 2, and 5 year) were higher in WD than DD (80.3% versus 55.9%; 65.1% versus 34.1%; 41.9% versus 7.8%; p < 0.0001) and (98% versus 88.1%; 95.6% versus 71.9%; 92.1% versus 36.5%; p < 0.0001) respectively. Conclusion WD and DD have distinct biological behaviors. Gross total resection is achievable in most WD; unlike DD, high-grade recurrence is uncommon. Treatment should therefore reflect these biologic differences by maximizing survivorship while avoiding unnecessarily extensive multivisceral resection. Synopsis The biological behaviors of well-differentiated and dedifferentiated liposarcomas differ significantly. This article presents outcomes of two different surgical approaches that were implemented at the UTMDACC, treating these tumors as different disease entities.     

Hyperpolarized product selective saturating‐excitations for determination of changes in metabolic reaction rates in real‐time

Investigation of hyperpolarized substrate metabolism has been showing utility in real‐time determination of in‐cell and in vivo enzymatic activities. Intracellular reaction rates may vary during the course of a measurement, even on the very short time scales of visibility on hyperpolarized MR, due to many factors such as the availability of the substrate and co‐factors in the intracellular space. Despite this potential variation, the kinetic analysis of hyperpolarized signals typically assumes that the same rate constant (and in many cases, the same rate) applies throughout the course of the reaction as observed via the build‐up and decay of the hyperpolarized signals. We demonstrate here an acquisition approach that can null the need for such an assumption and enable the detection of instantaneous changes in the rate of the reaction during an ex vivo hyperpolarized investigation, (i.e. in the course of the decay of one hyperpolarized substrate dose administered to a viable tissue sample ex vivo). This approach utilizes hyperpolarized product selective saturating‐excitation pulses. Similar pulses have been previously utilized in vivo for spectroscopic imaging. However, we show here favorable consequences to kinetic rate determinations in the preparations used. We implement this acquisition strategy for studies on perfused tissue slices and develop a theory that explains why this particular approach enables the determination of changes in enzymatic rates that are monitored via the chemical conversions of hyperpolarized substrates. Real‐time changes in intracellular reaction rates are demonstrated in perfused brain, liver, and xenograft breast cancer tissue slices and provide another potential differentiation parameter for tissue characterization.     

Augmentation of low-frequency ultrasound-induced clot disruption by hydroxyethyl starch is dependent on the duration and intensity of ultrasound exposure; an in vitro study

We investigated the synergistic effect between low-frequency ultrasound (US) and hydroxyethyl starch (HAES) on blood clot disruption, using different HAES concentrations, US duration and intensity. Human blood clots, 200 to 400 mg in weight, were placed in tubes containing 10 mL of normal saline alone or with HAES 0.1%, 1% or 2%. Clots were randomized to four intensities of US exposure: none, low, medium and high (maximal amplitude of motion at the tip of the horn: 0, 96, 144 and 192 micro m, respectively), and for three durations of US exposure (10, 20 and 40 s). After treatment, the clots were reweighed, and the percent differences in weights were calculated. US intensity, US duration and HAES concentration had a significant effect on the blood clot dissolution (p < 0.001 for all three variables). HAES augmented clot dissolution only when US intensity was medium or high. With low intensity, HAES did not augment clot lysis. CONCLUSIONS: microparticle-containing solutions, such as HAES, have a potential for augmenting clot disruption by US. This effect is highly dependent on US intensity.