Evaluation of Cell Therapy on Exercise Performance and Limb Perfusion in Peripheral Artery Disease: The CCTRN PACE Trial (Patients With Intermittent Claudication Injected With ALDH Bright Cells).

Background: Atherosclerotic peripheral artery disease affects 8% to 12% of Americans >65 years of age and is associated with a major decline in functional status, increased myocardial infarction and stroke rates, and increased risk of ischemic amputation. Current treatment strategies for claudication have limitations. PACE (Patients With Intermittent Claudication Injected With ALDH Bright Cells) is a National Heart, Lung, and Blood Institute-sponsored, randomized, double-blind, placebo-controlled, phase 2 exploratory clinical trial designed to assess the safety and efficacy of autologous bone marrow-derived aldehyde dehydrogenase bright (ALDHbr) cells in patients with peripheral artery disease and to explore associated claudication physiological mechanisms.

Reoperative cardiac surgery after long-term ventricular support therapy.

The use of investigational passive support devices continues to be evaluated in the treatment of heart failure. One concern with this technology is the future need for a reoperation such as coronary artery bypass surgery, placement of a left ventricular assist device or cardiac transplantation. In this report, we describe our experience with two patients who required reoperation after long-term use of a passive ventricular support device.

Perspectives on the development of a therapeutic HER-2 cancer vaccine.

With good reason, the majority of cancer vaccines tested, or being tested, have targeted the induction of anti-tumour CTL responses. However, the clinical success of monoclonal antibodies such as Rituximab/CD20, Trastuzumab/HER-2, Cetuximab/EGFR and Bevacisumab/VEGF suggests that their respective targets may also be relevant for cancer vaccines aiming at the induction of an effective humoral anti-tumour response to mimic, or potentially improve upon, the effects of monoclonal therapies. We report here an overview of the development of a protein vaccine targeting HER-2/neu, with an emphasis on the immunologic results obtained from the testing of the vaccine in animal models of disease and in toxicology programs, to its evaluation in three clinical trials in breast cancer patients.

Linked foreign T-cell help activates self-reactive CTL and inhibits tumor growth.

Transgenic mice expressing membrane-bound OVA under the rat insulin promoter, RIP-mOVA, has previously been suggested to display deletional tolerance toward the dominant CTL epitope, SIINFEKL, and provide an elegant model system to test the hypothesis that the lack of T cell help contributes to the tolerance. To understand how the CD8 tolerance is maintained in these mice, a set of neo-self-Ags, OVA, modified to contain a foreign Th peptide, were constructed and tested for their ability to induce CTL responses in RIP-mOVA mice. Immunization with these Th peptide-modified OVA molecules and not with the wild-type OVA induced self-reactive CTLs recognizing dominant CTL peptide, SIINFEKL.

HER-2 DNA and protein vaccines containing potent Th cell epitopes induce distinct protective and therapeutic antitumor responses in HER-2 transgenic mice.

Overexpression of the growth factor receptor HER-2 (c-erbB-2, neu) has transforming potential and occurs in approximately 20-30% of breast and ovarian cancers. HER-2 is a self Ag, but Abs and T cells specific for HER-2 have been isolated from cancer patients, suggesting HER-2 may be a good target for active immunotherapy. We constructed rat HER-2 DNA and protein vaccines containing potent Th cell epitopes derived from tetanus toxin and studied their potency in two strains of mice transgenic for the rat HER-2 molecule.

Comparison of dobutamine versus milrinone therapy in hospitalized patients awaiting cardiac transplantation: a prospective, randomized trial.

Background: The use of dobutamine or milrinone for inotropic support in patients with heart failure awaiting cardiac transplantation is largely arbitrary and based on institutional preference. The costs and effectiveness of these drugs have yet to be compared in a prospective, randomized study.

Methods: We compared clinical outcomes and costs associated with the use of dobutamine or milrinone in 36 hospitalized patients awaiting cardiac transplantation.

Ventricular dyssynchrony in dilated cardiomyopathy: the role of biventricular pacing in the treatment of congestive heart failure.

Despite advances in pharmacologic therapy, the prognosis of patients with advanced congestive heart failure (CHF) remains poor. Many of these patients have cardiac conduction abnormalities, such as left bundle-branch block or interventricular conduction delays, that can lead to ventricular dyssynchrony (abnormal ventricular activation that results in decreased ventricular filling and abnormal ventricular wall motion). Biventricular pacing is an alternative, nonpharmacologic therapy under active investigation for the treatment of CHF.

Percutaneous coronary intervention versus medical therapy for coronary allograft vasculopathy. One center's experience.

Background: Coronary allograft vasculopathy, a rapidly progressive form of atherosclerosis, remains the limiting factor in the long-term survival of heart transplant recipients. Some centers have attempted percutaneous coronary intervention to slow the disease process and thereby reduce mortality in these patients, but long-term follow-up data are scarce. We compared clinical outcomes in heart transplant recipients with coronary allograft vasculopathy who were treated either with percutaneous coronary intervention or with aggressive medical therapy alone.