Arterial gene transfer using pure DNA applied directly to a hydrogel-coated angioplasty balloon.

Direct arterial gene transfer has been previously achieved using double-balloon catheters and perforated balloons, in most cases facilitated by the use of cationic liposomes or viral vectors. These gene delivery systems, however, have been compromised by issues relating to efficacy and/or safety, and furthermore require that angioplasty be performed independent of gene transfer. We investigated the possibility that arterial gene transfer might be performed during balloon angioplasty by delivery of naked genetic material from a thin coat of hydrogel polymer applied to a standard angioplasty balloon.

Possible myocardial toxicity associated with interleukin-4 therapy.

Interleukin (IL)-4 is a cytokine produced by T lymphocytes, which may play a role in allergic inflammatory processes through its stimulatory effects on immunoglobulin E production and mast cells. In this report, we describe a patient with metastatic melanoma involving the heart who had biopsy-proven myocarditis after treatment with high-dose IL-4. Because of the uncharacteristic predominance of polymorphonuclear and mast cells in the inflammatory infiltrate of this patient's myocardium, we postulate a unique mechanism of IL-4-associated myocarditis.

Excimer laser-induced vasoreactivity.

Earlier generations of excimer lasers, designed for industrial or non-cardiovascular medical applications, have been previously shown consistently to induce vasorelaxation of vascular smooth muscle in vitro. Such lasers were typically characterized by pulse durations of < or = 15 nanoseconds (ns). Excimer lasers currently employed for cardiovascular applications were designed with longer pulse durations (up to 220 ns) to facilitate fibreoptic transmission.

Mechanisms and outcome of severe mitral regurgitation after Inoue balloon valvuloplasty. North American Inoue Balloon Investigators.

Objectives: The purpose of this study was to assess the incidence, mechanism and outcome of severe mitral regurgitation after treatment of mitral stenosis with percutaneous mitral valvuloplasty using the Inoue balloon.

Background: Severe mitral regurgitation occurs in up to 15% of percutaneous balloon valvuloplasty procedures for acquired mitral stenosis. The incidence and mechanism of production of mitral regurgitation with the recently introduced single-balloon Inoue technique have not been characterized.

Directional coronary atherectomy in heart transplant recipients.

Cardiac allograft vasculopathy is one of the most common obstacles to the long-term survival of heart transplant recipients. Percutaneous transluminal angioplasty has been used as a palliative treatment for discrete lesions caused by this disease, but it is often complicated by restenosis. This report describes two cases in which directional coronary atherectomy was used to treat the discrete lesions and explores the possible advantages of this intervention in lieu of the traditional approach.

Inhibition of endothelium-dependent vasorelaxation by sickle erythrocytes.

Interactions between erythrocytes and vascular endothelium have been implicated in the pathogenesis of vaso-occlusion in sickle cell anemia. Sickle erythrocytes adhere to endothelial cells and facilitate trapping of rigid sickle cells in microvessels. Compensatory dilation of precapillary arterioles may mitigate the occlusion.

Recommendations for training in vascular medicine. American College of Cardiology Peripheral Vascular Disease Committee.

Each trainee in vascular medicine must be eligible for the board certification examination of the American Board of Internal Medicine or its equivalent. Training faculty, preferably at least two members, should meet the qualifications and training requirements described in this report. They must be dedicated, effective teachers and should spend most of their time in research, education and patient care related to peripheral vascular diseases.

In vitro evidence that myocardial ischemia resulting from 5-fluorouracil chemotherapy is due to protein kinase C-mediated vasoconstriction of vascular smooth muscle.

5-Fluorouracil (5-FU) is a commonly employed chemotherapeutic agent. Among the various toxicities associated with 5-FU, cardiovascular toxicity, consisting principally of acute myocardial ischemia and/or myocardial infarction, has been reported in up to 8.5% of patients treated with this drug.

Limitations of color flow Doppler imaging in the quantification of valvular regurgitation: velocity of regurgitant jet, rather than volume, determines size of color Doppler image.

The objective of this study was to determine the validity of estimation of regurgitant volume by visual assessment of color flow Doppler display. An experimental apparatus was designed that is capable of ejecting precise volumes of echogenic material from one chamber to another under continuous color flow Doppler monitoring. The velocity of flow was altered independently by changing either the size of the orifice through which flow occurred or the ejection rate.

Comparison of results of percutaneous balloon valvuloplasty in patients with mild and moderate mitral stenosis to those with severe mitral stenosis. The North American Inoue Balloon Investigators.

Most reported studies of percutaneous balloon valvuloplasty in adults with acquired mitral stenosis have used patients with severely stenosed valves. The risks and benefits of valvuloplasty were examined in a multicenter registry of patients to determine whether balloon valvuloplasty can effectively dilate less severely obstructed valves, and to clarify the role of this procedure in symptomatic patients with mild and moderate mitral stenosis. The study groups were derived from the North American Inoue Balloon Valvuloplasty Registry.

Combined physiologic and anatomic assessment of percutaneous revascularization using a Doppler guidewire and ultrasound catheter.

Previous investigations have established the utility of intravascular ultrasound (IVUS) examination for the evaluation of arterial dimensions and qualitative changes following percutaneous revascularization. More recently, the feasibility of obtaining intravascular physiology findings before and/or after percutaneous revascularization by use of an intravascular Doppler Flowire (Cardiometrics) has been demonstrated. Accordingly, we investigated the feasibility of using this combined physiologic/anatomic approach to evaluate individuals undergoing percutaneous revascularization of stenotic or occluded coronary and peripheral arteries.

Coronary artery perforation during excimer laser coronary angioplasty. The percutaneous Excimer Laser Coronary Angioplasty Registry.

Objectives: The aim of this study was to analyze the risk of vessel perforation during excimer laser angioplasty.

Background: Vessel perforation is a serious complication of angioplasty.

Methods: A total of 764 patients had 858 stenoses treated with excimer laser angioplasty.

Proliferative activity in peripheral and coronary atherosclerotic plaque among patients undergoing percutaneous revascularization.

We evaluated the proliferative activity of human atherosclerotic lesions associated with active symptoms of ischemia, by assessing the expression of the proliferating cell nuclear antigen (PCNA). We confirmed in vitro that PCNA, an essential component of the DNA synthesis machinery, is selectively expressed in proliferating human vascular smooth muscle cells. 37 atherosclerotic lesions (18 primary and 19 restenotic) retrieved by directional atherectomy from either coronary or peripheral arteries were then studied for the expression of PCNA, using in situ hybridization or immunohistochemistry.

Relation between activated smooth-muscle cells in coronary-artery lesions and restenosis after atherectomy.

Background: Neointimal proliferation leading to restenosis frequently develops after coronary angioplasty. This process is associated with a change in vascular smooth-muscle cells from a contractile (quiescent) phenotype to a synthetic or proliferating (activated) one. We investigated whether the presence of activated smooth-muscle cells in coronary lesions at the time of coronary atherectomy predisposes patients to subsequent restenosis.

Effect of balloon size and stepwise inflation technique on the acute results of Inoue mitral commissurotomy. Inoue Balloon Catheter Investigators.

Currently percutaneous transvenous mitral commissurotomy (PTMC) is performed by most operators using stepwise inflation of the Inoue balloon beginning at a small diameter and increasing size by a sequence of inflations to nominal diameter. The effect of balloon size on procedure results using the Inoue balloon has not been evaluated. In 260 patients final balloon inflation was to nominal size in 42% of pts, larger than nominal size (overinflated) in 10%, and less than nominal size (underinflated) in 48% of pts.

Prevention of smooth muscle cell outgrowth from human atherosclerotic plaque by a recombinant cytotoxin specific for the epidermal growth factor receptor.

Smooth muscle cell proliferation in the intima of arteries is a principal event associated with vascular narrowing after balloon angioplasty and bypass surgery. Techniques for limiting smooth muscle cell proliferation, however, have not as yet yielded any therapeutic benefit for these conditions. This may reflect the present lack of sufficiently potent and specific inhibitors of smooth muscle cell proliferation.

Direct myocardial transfection in two animal models. Evaluation of parameters affecting gene expression and percutaneous gene delivery.

Background: Gene therapy represents a novel approach to the treatment of a variety of disease states. Direct injection of pure untreated DNA into skeletal and cardiac muscle is sufficient to perform gene transfer in vivo. Little information is available, however, regarding the extent to which individual parameters of direct gene delivery affect the efficiency of myocardial transfection.

How does angioplasty work? Serial analysis of human iliac arteries using intravascular ultrasound.

Background: Previous studies regarding the mechanism by which balloon angioplasty increases luminal patency have generally used animal models or postmortem specimens from occasional fatal cases of angioplasty performed in human patients. In either case, conclusions regarding participatory mechanisms have relied exclusively on nonserial, postangioplasty histopathological examination.

Methods And Results: In the present study, intravascular ultrasound examination was performed before and after balloon angioplasty in 40 consecutive patients with iliac artery stenoses.

Smooth muscle cell outgrowth from human atherosclerotic plaque: implications for the assessment of lesion biology.

Objectives: The purpose of this study was to determine whether the kinetics of smooth muscle cell outgrowth from in vitro explants of human atherosclerotic tissue is dependent on the nature of the atherosclerotic lesion in vivo.

Background: The use of techniques for percutaneous in vivo extraction of atherosclerotic plaque has provided the opportunity to study human atheroma-derived smooth muscle cells in culture. However, because of cell selection and changes in phenotype, in vitro findings may not always reflect the biologic properties of the vessel wall, particularly if cells are in culture for prolonged periods.