Search

OBJECTIVE: To model classical Bernard Soulier Syndrome in the zebrafish by targeting Gp1ba. RESULTS: We obtained gp1ba mutant embryos from Zebrafish International Resource Center and grew them to adulthood. The tail clips from these fish were used to prepare DNA and sequenced to identify heterozygotes. They were then bred to obtain homozygotes. The mutation was confirmed by DNA sequencing as a termination codon UAA in place of AAA codon at position 886 in the gp1ba transcript. Thus, at the Pro-295, the Gp1ba protein could be terminated. The blood from gp1ba homozygous and heterozygous mutants showed decreased ristocetin-mediated agglutination in the whole blood agglutination assay. The gp1ba heterozygous and homozygous larvae were subjected to a laser-assisted arterial thrombosis assay, and the results showed the prolonged occlusion in the caudal artery. These results suggested that the gp1ba mutant had a bleeding phenotype. The blood smears from the adult gp1ba, heterozygous and homozygous mutants, showed macrothrombocytes, similar to the human GP1BA deficiency that showed giant platelets. The bleeding assay on these heterozygous and homozygous mutants showed greater bleeding than wildtype, confirming the above findings. Taken together, the characterization of gp1ba zebrafish mutant suggested an autosomal dominant mode of inheritance. CONCLUSION: The zebrafish gp1ba mutant models classical Bernard Soulier Syndrome and could be used for reversing this phenotype to identify novel factors by the genome-wide piggyback knockdown method.

BackgroundWe aimed to evaluate for occult systolic dysfunction and the effect of methamphetamine cessation among patients with methamphetamine use (MU) and heart failure with preserved ejection fraction (HFpEF).MethodsA retrospective cohort of patients with HFpEF with serial echocardiograms was stratified by MU and evaluated using myocardial strain analysis on echocardiograms at baseline and 1year to measure global longitudinal strain (GLS). Contemporaneous controls with an ICD diagnosis of HF within 3days of an MU case were chosen.ResultsPatients with MU (n=31) were younger (49±10 vs 59±16years, p&nbsp

Reduced global longitudinal strain (GLS) by echocardiography is associated with worse survival in those who have aortic valve replacement. We developed Average Stretch QUantification of Endocardial Engraved Zones (SQUEEZ) as an automated imaging analysis technique that measures strain from 4D-cine

Context Obesity is a global problem and places individuals at risk for developing chronic metabolic disorders. The need for investigating simple, effective and sustaining approaches to weight loss cannot be overstated. Methods We performed a retrospective file analysis of patient files attending a 13-week weight loss program. Inclusion for analysis were files of adults (i.e., >18 years) completing the program consisting of chiropractic adjustments/spinal manipulative therapy augmented with diet/nutritional intervention, exercise and one-on-one counseling. Results Sixteen of 30 people (i.e., 53.33%) completed the program. Statistically and clinically significant changes were noted in weight and BMI measures based on pre-treatment (average weight = 190.46 lbs. and BMI = 30.94 kg/m 2 ) and comparative measurements (average weight = 174.94 lbs. and BMI = 28.50 kg/m 2 ). Conclusion A cohort of patients under enrolled in a weight loss program was described. This provides supporting evidence on the effectiveness of a multi-modal approach to weight loss implemented in a chiropractic clinic.

Introduction: Physical activity (PA) is associated with cardiovascular health benefits including prevention of age related cardiac remodeling, systolic and diastolic dysfunction, and adaptive pro-hypertrophic effect. In this study we aim to measure the associations between PA and LV structure and function in a diverse Hispanic/Latino population. Methods: Participants included 1,818 self-identified Hispanic/Latino men and women, age 45-74 from the Echocardiographic Study of Latinos (ECHO-SOL). Standard echo measures included M-mode, two-dimensional (2-D), spectral, tissue Doppler and color flow. Participants wore an Actical hip accelerometer for 1 week. Multivariable regression models were completed to relate PA to echocardiographic parameters. Results: The mean ± SE age for the cohort was 56 ±0.4, 57% were female, the prevalence of diabetes was 28%, hypertension 50%, hypercholesterolemia 49%, and coronary heart disease 7%. Average moderate to vigorous PA (MVPA) was 20.9 ± 1.1 min/day and sedentary time ±SE was 736.5 ± 8.1 min/day. In multivariable models adjusted for age, gender, diabetes, hypertension, hypercholesterolemia, coronary heart disease, alcohol and cigarette use we found the following: left atrium volume index (LAVI) decrease by quartiles of MVPA (p-value Conclusion: MVPA was significantly associated with lower LAVI. There was also a significant association with sedentary behavior. Our findings illustrate the complex relationship between PA, sedentary time and cardiac structure and function.

The purpose of this study was to analyze left ventricular obstruction in patients with hypertrophic cardiomyopathy (HCM) during exercise echocardiography.Despite the association of symptoms with left ventricular outflow tract obstruction in HCM, there exist paradoxical situations in which significant intraventricular gradients (50 mm Hg) at rest occur in conjunction with excellent exercise tolerance.To examine this phenomenon, we performed exercise echocardiography and analyzed the clinical status of 107 HCM patients with and without resting obstruction.At rest, 69 patients had no obstruction and 38 exhibited an intraventricular gradient, 9 of whom exhibited a decrease in gradient of at least 30 mm Hg (99.4 ± 35.5 mm Hg to 30.2 ± 14.3 mm Hg, p0.001) during exercise (paradoxical response to exercise [PRE]). The PRE patients presented with a significantly lower New York Heart Association clinical class and higher left ventricular volumes and arterial pressure both at rest and during exercise than HCM patients in whom the gradient increased or did not change during stress echocardiography. Finally, PRE patients exhibited a trend toward a reduced rate of cardiac events.Our study reports a subgroup of HCM patients, designated PRE based on a decreased intraventricular gradient during exercise. The reduced exertional obstruction may account for the better functional class and trend toward fewer clinical events in PRE patients.

The Right Care Initiative (RCI) is a California-wide, public-private coalition formed in 2007 to improve healthcare quality and outcomes. One RCI focus is cardiovascular disease (CVD) due to its high prevalence and evidence of specific healthcare improvement strategies. San Diego County, with its small set of large medical groups, was selected as a pilot project site. RCI leaders in San Diego hypothesized that outcome-focused meetings promoting the sharing of CVD prevention efforts among medical group leaders could lead to community-wide collaboration behind measurable action steps to achieve target goals. The high impact potential of the project attracted participation from the majority of San Diego medical groups. Two promising strategies were identified: (1) the delivery of bundled medication therapy consisting of aspirin, an angiotensin-converting enzyme (ACE) inhibitor, and a lipid-lowering medication for all CVD patients and patients > age 55 with diabetes, and (2) the use of pharmacists on care teams to assist with medication management. In addition, collaboration with the American Heart Association, Centers for Disease Control and Prevention, San Diego County Health and Human Services Agency and private citizens leverages existing heart-healthy lifestyle and screening programs. The participants also developed and plan to launch a local media outreach campaign to activate heart-healthy behavior adoption among San Diegans. To build team unity in the pilot project, San Diego medical group and community health leaders conducted monthly “University of Best Practices” conferences. At these non-competitive medical and academic meetings, presenters shared the successful quality improvement strategies of “high-performing” groups and participants experienced the benefits of working together. After several meetings, participants set a goal of reducing heart attacks and strokes in San Diego County by 50% within five years. Their “stretch goal” is to make the San Diego region the first “heart attack and stroke free zone.” The next step will be to track progress by routinely sharing group-specific data and action plans. Conclusions: Medical groups who normally compete in the clinical care arena found they could collaborate toward a common goal, as shown by agreement on action steps. The opportunity to regularly convene medical group leaders in San Diego proved critical to establishing necessary trust. This community-based approach is intended to catalyze the uptake of promising, evidence-based practices and improve care for San Diego’s high risk cardiovascular and diabetes patients. The recently announced national “Million Hearts” campaign synergizes closely with this pilot project’s focus on community-wide heart attack and stroke prevention.

Although the efficacy of recombinant tissue-type Plasminogen activator (rt-PA) in acute myocardial infarction has been demonstrated, little formal dose-ranging information is available. This study examined the use of duteplase, the double-chain rt-PA subsequently used in the Third International Study of infarct Survival, in a multicenter trial of 267 patients with evolving acute myocardial infarction assigned to receive 1 of 6 weight-adjusted doses. The primary end point was infarct vessel patency after 90 minutes of drug infusion. Patency was defined as Thrombolysis in Myocardial infarction trial grade 2 or 3 perfusion, and was determined by an independent core laboratory masked to treatment assignment. Patency was present in 48% of patients receiving the lowest dose range and 78% of those receiving the highest, with an association between thrombolytic dose and patency (p = 0.009). The frequency of serious bleeding complications also correlated with the total dose of rt-PA infused (p = 0.003). Bleeding complications were primarily related to instrumentation; blood toss requiring transfusion or otherwise deemed clinically significant occurred in 12% of patients (central nervous system hemorrhage occurred in 1.1%). Thus, higher doses of rt-PA are associated both with increased efficacy and increased risk of serious bleeding complications. Weight-adjusted dosing may provide an optimal risk-benefit ratio for thrombolysis during acute myocardial infarction.

BATHE is an acronym for Background, Affect, Trouble, Handling, and Empathy and refers to specific questions or comments incorporated into a standard medical interview. The BATHE technique was developed as a rapid psychosocial intervention for the assessment of psychological factors that may contribute to patients' physical complaints. The present research was designed to determine whether the use of BATHE significantly increased patient satisfaction during a visit to a family physician.Four family physicians in a busy urban family practice center were involved in the study. Two physicians were instructed to use the BATHE protocols until data had been collected from 10 patients and then to proceed in their usual fashion with their next 10 patients. The other two physicians conducted their interview as usual with their first 10 patients and then used BATHE with the following 10 patients. All patients were asked to complete a satisfaction survey following their consultation.BATHEd patients responded with significantly higher ratings for 8 of the 11 satisfaction measures, including those related to information provided, perception of physician concern, and likelihood of recommending the physician to others.The results of this pilot study support the use of BATHE with primary care patients, as it increases patient satisfaction, possibly by helping patients sense that their physician is sympathetic and concerned.

Although phosphoinositide 3-kinases (PI3Ks) play beneficial pro-cell survival roles during tissue ischemia, some isoforms (γ and δ) paradoxically contribute to the inflammation that damages these same tissues upon reperfusion. We therefore considered the possibility that selectively inhibiting proinflammatory PI3K isoforms during the reperfusion phase could ultimately limit overall tissue damage seen in ischemia/reperfusion injuries such as myocardial infarction. Panreactive and isoform-restricted PI3K inhibitors were identified by screening a novel chemical family; molecular modeling studies attributed isoform specificity based on rotational freedom of substituent groups. One compound (TG100-115) identified as a selective PI3K γ/δ inhibitor potently inhibited edema and inflammation in response to multiple mediators known to participate in myocardial infarction, including vascular endothelial growth factor and platelet-activating factor; by contrast, endothelial cell mitogenesis, a repair process important to tissue survival after ischemic damage, was not disrupted. In rigorous animal MI models, TG100-115 provided potent cardioprotection, reducing infarct development and preserving myocardial function. Importantly, this was achieved when dosing well after myocardial reperfusion (up to 3 h after), the same time period when patients are most accessible for therapeutic intervention. In conclusion, by targeting pathologic events occurring relatively late in myocardial damage, we have identified a potential means of addressing an elusive clinical goal: meaningful cardioprotection in the postreperfusion time period.

This study was designed to analyze the results of fibrinolytic treatment (FT) in a large single-center group of patients with prosthetic heart valve thrombosis (PHVT).Fibrinolytic treatment of PHVT represents an alternative to surgery, but is still controversial because of the risk of embolism.A total of 110 consecutive patients presenting with 127 instances of PHVT received FT between 1978 and 2001. The diagnosis of PHVT was established mainly by fluoroscopy and/or echocardiography. The first fibrinolytic agent used was streptokinase (SK) in 49 cases, urokinase (UK) in 41 cases, and recombinant tissue-type plasminogen activator (rtPA) in 37 cases. A second FT was consecutively infused in 38 patients (30%) and a third FT in 11 others. The efficacy of FT was assessed from hemodynamic parameters derived from echographic examinations as well as on clinical grounds.Complete resolution of hemodynamic abnormalities was seen in 90/127 patients, partial resolution in 22/127 patients, and no change in 15/127 patients after one or more consecutive fibrinolytic regimens. When SK or rtPA were used as the first fibrinolytic agent, they appeared significantly superior to UK in terms of valve reopening. Fifteen patients died. Severe hemorrhagic complications were observed in six patients. Nineteen documented embolic events occurred during FT. Finally, PHVT recurred in 24 patients, 17 of whom were retreated with lytic agents.These results indicate that FT is effective in most cases of PHVT, regardless of prosthesis or site involved. However, embolism, hemorrhage, and death were not uncommon after lytic therapy of left-sided PHVT, limiting its application to patients at high risk with alternative treatment.

We have presented recommendations for the optimum acquisition of quantitative two-dimensional data in the current echocardiographic environment. It is likely that advances in imaging may enhance or supplement these approaches. For example, three-dimensional reconstruction methods may greatly augment the accuracy of volume determination if they become more efficient. The development of three-dimensional methods will depend in turn on vastly improved transthoracic resolution similar to that now obtainable by transesophageal echocardiography. Better resolution will also make the use of more direct methods of measuring myocardial mass practical. For example, if the epicardium were well resolved in the long-axis apical views, the myocardial shell volume could be measured directly by the biplane method of discs rather than extrapolating myocardial thickness from a single short-axis view. At present, it is our opinion that current technology justifies the clinical use of the quantitative two-dimensional methods described in this article. When technically feasible, and if resources permit, we recommend the routine reporting of left ventricular ejection fraction, diastolic volume, mass, and wall motion score.

The field of myocardial regeneration (angiogenesis and myogenesis) might prove to play an important role in the future management of cardiovascular disease. Stem cells are currently undergoing testing in Phase I and Phase II clinical trials. Methods of delivery will affect the outcome of such therapies, perhaps significantly. This document provides suggested guidance in 4 methods of delivery: endocardial, intracoronary, coronary sinus, and epicardial.