Dobutamine improves thoracic aortic blood flow during off-pump coronary artery bypass surgery: results of a prospective randomised controlled trial.

OBJECTIVE: Dobutamine is commonly used to improve ventricular performance in cardiac surgery. The aim of this prospective randomised controlled study was to assess the effectiveness of using low doses of dobutamine during off-pump coronary artery bypass (OPCAB) surgery in order to reduce haemodynamic compromise due to heart displacement. METHODS: Thirty-two patients undergoing elective coronary artery bypass grafting (CABG) surgery using OPCAB technique for more than two vessels were approached and recruited. We analysed the changes in the thoracic aortic blood flow (TABF) during OPCAB using transoesophageal Doppler and by other conventional monitoring methods as cardiac output, invasive pulmonary and radial pressures and mixed venous oxygen saturation. RESULTS: The two groups were similar in preoperative characteristics. No postoperative complications were observed in the study patients. The heart rate, right atrial pressure, cardiac output measured by thermodilution and TABF changed significantly during the procedure. Also significant changes in descending thoracic aortic diameter were observed. The postoperative creatinine was significantly lower in the dobutamine group (P=0.04). Dobutamine was found responsible for the improvement in the descending TABF (P=0.006). CONCLUSIONS: This study showed that intra-operative intravenous infusion of dobutamine at 5 microg/kg per min in routine OPCAB patients safely increased cardiac output even without such changes been detected by conventional monitoring methods.     

Phase II study of denileukin diftitox for relapsed/refractory B-Cell non-Hodgkin's lymphoma.

PURPOSE: Denileukin diftitox is a fusion protein combining diphtheria toxin and interleukin-2 (IL-2) that targets tumor cells expressing the IL-2 receptor. Its efficacy has been shown in CD25+ cutaneous T-cell lymphoma, but not in B-cell non-Hodgkin's lymphoma (NHL). A phase II study was performed to evaluate the efficacy and tolerability of denileukin diftitox for relapsed or refractory B-cell NHL. PATIENTS AND METHODS: Patients with relapsed or refractory B-cell NHL were eligible. Tumor CD25 expression was determined by immunohistochemistry or flow cytometry. Denileukin diftitox was administered intravenously at a dose of 18 microg/kg once daily for 5 days every 3 weeks, up to eight cycles. RESULTS: Of the 45 patients assessable for response, 32 (71%) were refractory to the last chemotherapy treatment, and all were previously treated with rituximab. Three complete responses (6.7%) and eight partial responses (17.8%) were observed, for an overall response rate of 24.5%. Nine patients (20%) had stable disease. Objective response rates were similar in CD25+ (22%) and CD25- histologies (29%), as were stable disease rates (22% and 18%, respectively). For responding patients, the median time to treatment failure was 7 months, with a median follow-up in survivors of 18 months (range, 9 to 28 months), and the projected progression-free survival at 20 months was 24% (95% CI, 0% to 60%). Most toxicities were low-grade and transient. CONCLUSION: Denileukin diftitox seems to be effective in relapsed or refractory, CD25+ and CD25- B-cell NHL and is well-tolerated at the dosage evaluated. Evaluation of denileukin diftitox in combination with other agents may be warranted.     

Phase II study of proteasome inhibitor bortezomib in relapsed or refractory B-cell non-Hodgkin's lymphoma.

PURPOSE: Evaluate efficacy and toxicity of bortezomib in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. PATIENTS AND METHODS: Patients were stratified, based on preclinical data, into arm A (mantle-cell lymphoma) or arm B (other B-cell lymphomas) without limitation in number of prior therapies. Bortezomib was administered as an intravenous push (1.5 mg/m2) on days 1, 4, 8, and 11 every 21 days for a maximum of six cycles. RESULTS: Sixty patients with a median number of prior therapies of 3.5 (range, one to 12 therapies) were enrolled; 33 patients were in arm A and 27 were in arm B, including 12 diffuse large B-cell lymphomas, five follicular lymphomas (FL), three transformed FLs, four small lymphocytic lymphomas (SLL), two Waldenstrom's macroglobulinemias (WM), and one marginal zone lymphoma. In arm A, 12 of 29 assessable patients responded (six complete responses [CR] and six partial responses [PR]) for an overall response rate (ORR) of 41% (95% CI, 24% to 61%), and a median time to progression not reached yet, with a median follow-up of 9.3 months (range, 1.7 to 24 months). In arm B, four of 21 assessable patients responded (one SLL patient had a CR, one FL patient had a CR unconfirmed, one diffuse large B-cell lymphoma patient had a PR, and one WM patient had a PR) for an ORR of 19% (95% CI, 5% to 42%). Grade 3 toxicity included thrombocytopenia (47%), gastrointestinal (20%), fatigue (13%), neutropenia (10%), and peripheral neuropathy (5%). Grade 4 toxicity occurred in nine patients (15%), and three deaths from progression of disease occurred within 30 days of withdrawal from study. CONCLUSION: Bortezomib showed promising activity in relapsed mantle-cell lymphoma and encouraging results in other B-cell lymphomas. Future studies will explore bortezomib in combination with other cytotoxic or biologic agents.     

Multidetector-row computed tomography and magnetic resonance imaging of atherosclerotic lesions in human ex vivo coronary arteries

In the present study, we tested the ability of multidetector-row computed tomography (MDCT) and magnetic resonance imaging (MRI) to identify and retrospectively characterize atherosclerotic lesions in human ex vivo coronary arteries. Thirteen ex vivo hearts were studied with MDCT and MRI. MDCT-images were obtained with an isotropic voxel size of 0.6mm(3). MR images were obtained with an in-plane resolution of 195 microm and 3mm slice thickness. All images were matched with histopathology sections. For both modalities, the sensitivity for the detection of any atherosclerotic lesion was evaluated, and a retrospective analysis of plaque morphology according to criteria defined by the American Heart Association (AHA) was performed. At histopathology, 28 atherosclerotic lesions were found. 21 and 23 of these lesions were identified by MDCT and MRI, respectively. Both modalities detected a small number of false-positive lesions. After retrospective matching with histopathology, MDCT as well as MRI were able to differentiate typical morpholocigal features for fatty, fibrous or calcified plaque components. Using the information presented in this study, in vivo coronary artery wall imaging using MDCT as well as MRI could be facilitated and supported for future investigations on this subject.