Structure and dynamic regulation of Src-family kinases.

Src-family kinases are modular signaling proteins involved in a diverse array of cellular processes. All members of the Src family share the same domain organization, with modular SH3, SH2 and kinase domains followed by a C-terminal negative regulatory tail. X-ray crystallographic analyses of several Src family members have revealed critical roles for the SH3 and SH2 domains in the down-regulation of the kinase domain. This review focuses on biological, biophysical, and computational studies that reveal conformationally distinct active states within this unique kinase family.

Mortality and need for reoperation in patients with mild-to-moderate asymptomatic aortic valve disease undergoing coronary artery bypass graft alone.

BACKGROUND: Patients presenting for coronary artery bypass graft (CABG) surgery may have concurrent asymptomatic aortic stenosis (AS) or aortic insufficiency (AI). This retrospective study was performed to evaluate outcomes in patients with aortic valve disease undergoing CABG with or without aortic valve replacement (AVR). METHODS: Study groups included 414 patients undergoing combined AVR and CABG (AVR-CABG group) and 62 patients with asymptomatic mild-to-moderate AS, AI, or both undergoing CABG but not AVR (CABG group). End points included 30-day mortality rate, time to cardiac mortality, time to all-cause mortality, and time to aortic valve reoperation. Reoperation refers to surgery for replacement of the native aortic valve in the CABG group or replacement of the prosthetic aortic valve in the AVR-CABG group. Important patient characteristics affecting outcomes were determined by using Cox proportional-hazard analysis. These variables were then included in multivariable analyses by using logistic regression analysis and Cox proportional-hazard modeling to compare outcomes between each patient group. RESULTS: No difference was seen in any of the mortality end points between the CABG group and the AVR-CABG group after controlling for significant differences between the groups. However, the need for reoperation for AVR was significantly higher for the CABG group than the AVR-CABG group. For patients followed for up to 6 years, the estimated need for aortic valve reoperation was 24.3% in the CABG group versus 3% in the AVR-CABG group. CONCLUSION: On the basis of these results, patients with asymptomatic AS or AI should be considered for AVR at the time of CABG.

Higher T-wave amplitude associated with better prognosis in patients receiving thrombolytic therapy for acute myocardial infarction (a GUSTO-I substudy). Global Utilization of Streptokinase and Tissue plasminogen Activator for Occluded Coronary Arteries.

Increased T-wave amplitude is one of the earliest electrocardiographic (ECG) changes following coronary artery occlusion. Therefore, higher T waves in the presenting electrocardiogram should represent earlier time to treatment and thus be associated with lower mortality following thrombolytic therapy. However, T-wave amplitude has never been evaluated as a prognostic marker in this setting. We examined clinical outcomes in 3,317 patients with acute myocardial infarction (AMI) who underwent thrombolysis in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-I) Study. Patients were classified as either those with high T waves or those with low T waves. Higher T waves were defined as those >98th percentile of the upper limit of normal. T-wave amplitude was also evaluated as a continuous variable according to infarct location (maximum T-wave amplitude) and as the amount of excess T-wave amplitude above normal (excess T-wave amplitude). Patients with higher T waves had lower 30-day mortality than those without (5.2% vs 8.6%, p = 0.001) and were less likely to develop congestive heart failure (15% vs 24%, p <0.001) or cardiogenic shock (6.1% vs 8.6%, p = 0.023). Higher maximum T-wave amplitude and excess T-wave amplitude were predictive of lower 30-day mortality (chi-square = 67, p <0.001 and chi-square = 33, p <0.001, respectively). These differences remain significant after controlling for other prognostic baseline ECG variables. In addition, T-wave amplitude added prognostic significance after controlling for time to treatment. T-wave amplitude, an often-overlooked component of the electrocardiogram, can add significant prognostic information in initial evaluation of patients with AMI.

A randomized trial of vascular hemostasis techniques to reduce femoral vascular complications after coronary intervention.

This report details a prospectively randomized clinical trial comparing mechanical clamp compression to hand applied pressure for attaining vascular hemostasis after coronary intervention. Effectiveness was determined by comparing the incidence of femoral vascular complications resulting from each of the 2 techniques. Eligible participants included 778 consecutive patients scheduled for percutaneous coronary intervention over an 8-month period. An unselected cohort of the eligible patients (n = 592), determined by the availability of cross-trained clinicians, underwent follow-up serial physical examinations by blinded observers for the duration of their hospital stay. A second, similarly determined cohort (n = 390), underwent color-duplex ultrasonography within 24 hours of sheath removal. Baseline demographic and clinical characteristics, sheath removal parameters, and subsequent outcomes were collected prospectively. The primary end point was a composite of ultrasound-defined femoral vascular complications: femoral artery thrombosis, echogenic hematoma, pseudoaneurysm, or arteriovenous fistulae formation. Complications diagnosed by physical examination constituted the second fundamental end point and included: persistent oozing, ecchymosis, hematoma, bruit, and pulsatile mass. Compared to manual compression, mechanical clamp hemostasis reduced the primary adverse end point by 63% (p = 0.041). Physical examination detected ecchymosis, oozing, and hematomas at equally high frequencies in the two cohorts. Although 65% of the patients in both treatment groups encountered at least one of these cosmetic complications, the diagnoses made by physical examination did not correlate with ultrasound-defined pathology. Multivariable stepwise logistic regression analysis identified a relationship of advanced age and lower body weight to vascular complications. Utilization of a mechanical clamp rather than conventional hand pressure to attain vascular hemostasis significantly reduces ultrasound-defined femoral vascular pathology. Discrepancies between physical examination and ultrasound diagnoses challenge the utility of clinical assessment alone and establish ultrasound as the diagnostic modality of choice.

Percutaneous stenting of superior vena cava syndrome: a case report and review of the literature.

Superior vena cava syndrome (SVCS) is a distressing manifestation of benign or malignant disease obstructing return of blood flow through the superior vena cava (SVC). Treatment, often centering around management of the underlying illness, may be slow in relieving symptoms, relying on the recruitment of collateral veins to reestablish blood flow. Percutaneous delivery of metallic stents into the vena cava has been used with success to relieve obstruction to blood flow quickly and completely. We present the case of a patient with complete occlusion of the SVC who underwent successful vena caval revascularization with placement of balloon expandable metallic stents. We also review published reports on the use of stents for SVCS. Results from several series demonstrate that stents can be used with excellent results. Response rates in these series reviewed range from 68% to 100%. Recurrence of symptoms occurred in 4% to 45% of patients but could often be treated with anticoagulation, angioplasty of the stented area, or repeat stenting. Stenting has been used successfully in patients with malignant diseases and in the less common cases of SVCS from a benign etiology. Complications are uncommon and usually of minor consequence. Anticoagulation, thrombolytics, and thrombectomy or atherectomy catheters have also been used during or following stent implantation although their use remains primarily empiric. Percutaneous treatment of SVC obstruction offers patients hope for prompt and dramatic relief from the symptoms of SVCS.