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In 1992, the American Society of Echocardiography published a report of the Sonographer Education and Training Committee's recommendations for education of sonographers who perform echocardiographic procedures. Since the publication of the original document, there has been continual progress in technology with the development of more sophisticated diagnostic applications that allow more information to be obtained from echocardiographic procedures. These recent changes in the clinical application of echocardiography should be included in all cardiac sonographer education programs. The American Society of Echocardiography, a professional society that currently represents approximately 2500 cardiac sonographers, provides these updated guidelines.

Occupational health hazards in ultrasonography are becoming more prevalent as the field continues to grow. Eye strain, musculoskeletal pain or injury, carpal tunnel syndrome, repetitive strain injuries, stress, burnout, and other hazards have been addressed as concerns in other studies and surveys. These topics are discussed, as well as the possible preventive measures that may be used to maximize and maintain the ultrasonographer's well-being throughout his or her career. (J Am Soc Echocardiogr 1997;10:363-6.)

The combination of fludarabine, cyclophosphamide, and rituximab (FC-R) shows significant in vitro synergism and may improve patient outcome with little overlapping toxicity.Between December 2000 and June 2005, 77 patients completed therapy after a median of 4 cycles of FC-R (fludarabine at a dose of 25 mg/m2 intravenously [i.v.] on Days 1-3, cyclophosphamide at a dose of 250 mg/m2 i.v. on Days 1-3, and rituximab at a dose of 375 mg/m2 on Day 1). The median age of the patients was 59 years, 65% were male; 31% had previously untreated disease; and 44% had chronic lymphocytic leukemia (CLL), 29% had follicular lymphoma, and 27% other indolent lymphoid malignancies. In addition to standard disease response criteria, patients underwent evaluation using flow cytometric and/or molecular studies.Objective responses (OR) and complete responses (CR) were observed in 83% and 42%, respectively, of evaluable patients (n=76), respectively. For patients with CLL, the respective OR and CR rates were 100% and 67% as firstline therapy, and 95% and 14% as salvage therapy. For patients with follicular lymphoma, the respective OR and CR rates were 100% and 86% as firstline therapy, and 87% and 67% as salvage therapy. Responders who had no detectable disease on flow cytometric and/or molecular studies experienced prolonged remissions with no recurrences reported at a median 25 months of follow-up. Peripheral stem cell collection using stem cell factor plus granulocyte-colony-stimulating factor was successful in 10 of 13 patients who underwent mobilization (77%).FC-R is highly active as initial or salvage therapy in patients with CLL or indolent non-Hodgkin lymphoma. Collection of autologous stem cells during molecular remission is feasible and may facilitate future exploration of high-dose therapy in these patients.

This series on contrast echocardiography has previously discussed the value of this technique for the improvement of endocardial border definition in technically challenging patients. The echocardiographic assessment of left ventricular (LV) regional performance can be significantly improved by using LV opacification (LVO) produced by the injection of contrast microbubbles into a peripheral vein. On the basis of years of investigational work, it is now apparent that myocardial contrast echocardiography (MCE) may offer an additional clinical benefit by assessing regional myocardial perfusion. Investigators have recently presented encouraging results using echocardiographic contrast agents for the assessment of myocardial perfusion under optimal imaging conditions. In this final article of the series on contrast, we will provide some basic information on the use of MCE for the assessment of myocardial perfusion. As always, we refer you to more detailed explanations in the listed references. Currently, nuclear imaging that uses thallium or sestamibi scintigraphy is the only clinical technique used to assess myocardial perfusion. In comparison, MCE is less expensive, portable, and does not use ionizing radiation. MCE uses an intravascular tracer and demonstrates better spatial resolution. Contrast microbubbles injected into a peripheral vein, the aortic root, or directly into the coronary arteries are designed to travel through the cardiovascular circulation in a manner similar to red blood cells. These microbubbles not only fill the LV cavity as see during LVO, but they also traverse the epicardial coronary vessels into the myocardial capillaries. The concentration of microbubbles in the myocardial capillary bed is far less than found within the LV cavity after an intravenous injection, so specialized techniques have been developed to detect contrast microbubbles for the assessment of myocardial perfusion. These techniques and the clinical benefits of assessing myocardial perfusion will be discussed in more detail.

Abstract 883 ABT-263, a novel orally bioavailable BH3 mimetic, binds with high affinity (Ki ≤ 1nM) and inhibits multiple antiapoptotic Bcl-2 family proteins. In vitro, ABT-263 potently induces apoptosis (EC50 ≤ 1μM) in Bcl-2 overexpressing human lymphoma cell lines and primary CLL cells. Preclinical mechanism-based toxicities include inhibition of spermatogenesis, reduction in circulating lymphocytes and decreased survival of circulating platelets, reflecting inhibition of Bcl-w, Bcl-2 and Bcl-XL, respectively. Study M06-873 is a phase 1/2a dose-escalation trial employing a continuous reassessment method (CRM) to evaluate ABT-263 PK, safety and antitumor activity of two dosing schedules in pts with relapsed or refractory CLL. Tumor responses were evaluated by the NCI-WG criteria. Pts were initially dosed on d1-14 of a 21d cycle with 10-250 mg ABT-263. To ameliorate the impact of thrombocytopenia (TCP) due to on-target Bcl-XL inhibition-induced platelet apoptosis, a 100 mg lead-in dose for 7d followed by continuous 21/21d dosing (up to 300mg/d) was investigated. This study has completed enrollment at 300 mg with 29 pts (15 on a 14/21d; 14 on a 21/21d schedule) as of June 2009. The PK exposure of ABT-263 was approximately dose-proportional from 10-300 mg with a terminal half-life of 11 h. Platelet nadirs were transient, occurring on d3-5 followed by partial recovery due to compensatory increased megakaryopoiesis during continued dosing. Lead-in dosing reduced the early platelet nadir, and minimized fluctuations in platelet count observed with intermittent dosing. Circulating platelet count dropped maximally during cycle 1 by an average 12%, 57%, 68% and 70% from baseline at 10 mg, 110 mg, 200 and 250 mg for the 14/21d schedule, and an average of 52%, 63%, 63% and 68% from baseline at 125 mg, 200 mg, 250 mg and 300 mg for the 21/21d schedule. Of the 21 evaluable pts, 2 had radiographically confirmed partial responses (99% and 79% reductions) and 3 had as yet unconfirmed nodal regression (100%, 71% and 55%). 7 pts maintained a ≥50% decrease in circulating absolute lymphocyte count for ≥ 2 months with 2 pts having PR by physical examination; the overall response rate was 33%. Stable disease was noted in 8 pts and 2 pts had progressive disease. Responses tend to be durable, with the median PFS not yet reached while the median time on study is 9 mos (range 0.63 - 18.4 mos). The most common adverse events (AE) were diarrhea (52%), nausea (44%), vomiting (24%), fatigue (24%) thrombocytopenia (TCP; 20%) and neutropenia (12%). Dose limiting toxicities (DLT) were observed in 3 pts on the 14/21d schedule; 2 at 110mg (hospitalization & Grade 4 TCP) and 1 at 250 mg (Grade 4 TCP). Among the 14 pts on the 21/21d schedule, 3 pts experienced DLT; 1 at 200 mg (Grade 4 TCP); 1 at 250 mg (Grade 2 nausea) and 1 at 300 mg (Grade 4 TCP). ABT-263 was well-tolerated and had favorable PK and acceptable safety profiles. One week 100mg/d lead-in followed by continuous dosing minimizes platelet nadir and cycle variability. Based on the 21/21d continuous dosing data, the CRM model projection for MTD converged. The recommended phase 2 dose is 100 mg 7-d lead-in followed by 250 mg/d continuous dosing. Disclosures: Roberts: Abbott : Research Funding; Genentech: Research Funding. Off Label Use: ABT-263 is an experimental drug that is not yet registered. It is designed to induce apoptosis in tumor cells.. Brown:Celgene: Research Funding; Genzyme: Research Funding. Wierda:GSK: Consultancy; Ligand: Consultancy; Genentech: Consultancy; MEDIMMUNE: Consultancy; ABBOTT: Consultancy; TRUBION: Consultancy; BAYER, SANOFI-AVENTIS, MEMGEN, GENITOPE, GENMAB, SUNESIS, ABBOTT, GSK: Research Funding; GENENTECH: Honoraria; CELGENE: Speakers Bureau. Xiong:Abbott: Employment. Cui:Abbott: Employment. Busman:Abbott: Employment. Enschede:Abbott: Employment. Krivoshik:Abbott: Employment. Humerickhouse:Abbott: Employment.