Intravascular ultrasound predictors of restenosis after percutaneous transcatheter coronary revascularization

OBJECTIVES: This study sought to evaluate preintervention and postintervention intravascular ultrasound studies for potential predictors of angiographic restenosis and to use ultrasound predictors of restenosis to enhance our understanding of the pathophysiology of the restenosis disease process. BACKGROUND: Restenosis remains the major limitation of percutaneous transcatheter coronary revascularization. Although its mechanisms remain incompletely understood, numerous studies have identified some of the clinical, anatomic and procedural risk factors for restenosis. Intravascular ultrasound imaging of target lesions before and after catheter-based treatment consistently demonstrates more target lesion calcium, more extensive reference segment atherosclerosis, smaller final lumen dimensions, significant residual plaque burden and a greater degree of tissue trauma than is evident by angiography. METHODS: Intravascular ultrasound studies were performed in 360 nonstented native coronary artery lesions (final diameter stenosis 18 +/- 11%) in 351 patients for whom follow-up angiographic data were available 6.4 +/- 3.6 months later. Hospital charts were reviewed, and qualitative and quantitative coronary angiographic and intravascular ultrasound analyses were performed by independent core laboratories. Four dependent angiographic end points were tested: restenosis as a binary definition (> or = 50% diameter stenosis at follow-up) was the primary end point; follow-up diameter stenosis, late lumen loss and follow-up minimal lumen diameter were the secondary end points. RESULTS: Reference vessel size, the preintervention quantitative coronary angiographic assessment of lesion severity and the postintervention intravascular ultrasound cross-sectional measurements predicted the late angiographic results. In particular, the intravascular ultrasound postintervention cross-sectional narrowing (plaque plus media cross-sectional area divided by external elastic membrane cross-sectional area) predicted the primary end point (restenosis) and two of the three secondary end points (follow-up diameter stenosis and late lumen loss) and was therefore the most consistent predictor of restenosis. CONCLUSIONS: Intravascular ultrasound variables are more powerful and consistent predictors of angiographic restenosis than currently accepted clinical or angiographic risk factors.     

Coronary artery restenosis after balloon angioplasty in humans is associated with circumferential coronary constriction

Therapies that inhibit intimal hyperplasia do not prevent restenosis after coronary artery balloon angioplasty, suggesting that additional mechanisms may be responsible for restenosis in humans. Using an intravascular ultrasound (Hewlett-Packard Sonos Intravascular Imaging System). 3.5F, 30-MHz (Boston Scientific) monorail imaging catheter, we studied 17 patients with clinical and angiographic restenosis at an average (mean +/- SD) of 7 +/- 6 months after balloon angioplasty (13 men age, 71 +/- 10 years; 12 left anterior descending coronary arteries, 4 right coronary arteries, and 1 left circumflex coronary artery) The lumen area (L.A), vessel wall area (VWA), and total cross-sectional area (CSA) within the external elastic lamina were measured at the restenosis site and at proximal and distal reference sites, which were defined as adjacent segments with the least amount of plaque. Consistent with coronary angiography findings, decreased LA at the restenotic site was detected in all 17 patients. The unique finding was that total CSA at the restenotic site was significantly decreased compared with both proximal and distal reference sites (10.1 +/- 2.4 versus 14.8 +/- 3.2 mm2 and 10.1 +/- 2.4 versus 13.8 +/- 3.1 mm2, respectively, P < .001), whereas VWA (intima plus media) was slightly increased at the angioplasty site compared with both proximal and distal reference sites (8.0 +/- 2.3 versus 7.6 +/- 2.3 mm2 and 8.0 +/- 2.3 versus 6.7 +/- 2.3 mm2, respectively, P = NS). Eighty-three percent of the loss in LA at the restenotic site was due to constriction of the total CSA, while the increase in VWA at the restenotic site accounted for only a 17% loss in LA. We then compared these results with the morphology of coronary artery segments in 14 patients without restenosis. These coronary artery segments had been previously treated with balloon angioplasty (7 +/- 5 months). Unlike that in restenotic lesions, the total CSA within the external elastic lamina at the sites of previous angioplasty was similar to that in distal and proximal reference sites (P = NS). Significant and consistent reduction in arterial CSA, with a minor increase in VWA, characterizes human coronary lesions that cause angiographic restenosis. These data suggest that in humans, "recoil" and/or vascular contraction with healing in response to balloon injury is a major contributor to restenosis after balloon angioplasty.     

Intravascular ultrasound findings after successful primary angioplasty for acute myocardial infarction: predictors of abrupt occlusion

OBJECTIVES: This study sought to evaluate the intravascular structure as depicted by intravascular ultrasound after successful primary angioplasty (i.e., without thrombolytic therapy) for acute myocardial infarction and to investigate the related predictors of acute coronary occlusion. BACKGROUND: The usefulness of primary angioplasty for acute myocardial infarction is still limited by early reocclusion. There are few data regarding the intravascular ultrasound findings after primary angioplasty. METHODS: Intravascular ultrasound was performed in 27 patients after successful primary angioplasty. Repeat coronary angiography was performed 15 min later, on the following day and 1 month after angioplasty. RESULTS: Abrupt occlusion occurred in 8 of 27 patients. Angiographic variables in patients with versus those without abrupt occlusion were not significantly different. Intravascular ultrasound disclosed a significantly smaller lumen area ([mean +/- SD] 2.49 +/- 0.72 vs. 5.06 +/- 1.52 mm2, p < 0.001) and a significantly greater percent plaque area (80.5 +/- 9.1% vs. 63.7 +/- 7.8%, p < 0.001) in patients with abrupt occlusion. There was no significant difference in external elastic membrane cross-sectional area. We classified the ultrasound appearance of the intravascular structure as smooth, irregular or filled. Abrupt occlusion occurred in none of 6 patients with a smooth intravascular structure, 24% of 17 patients with an irregular structure and in all 4 with a filled structure (p < 0.05). In the latter group, the lumen was filled with bright speckled or low echogenic material, although angiography revealed excellent coronary dilation in all these arteries. CONCLUSIONS: Intravascular ultrasound revealed a narrow lumen in coronary arteries showing abrupt occlusion after successful primary angioplasty, even though angiography disclosed successful dilation. Arteries with a lumen filled with bright speckled or low echogenic material frequently develop abrupt occlusion.     

Anti-atherogenicity in women does not prevent restenosis after balloon angioplasty

To test the hypothesis that anti-atherogenicity in women exerts beneficial effects to prevent restenosis formation after coronary angioplasty, we studied 493 men (988 lesions) and 81 women (159 lesions), aged 40-60 years, who had undergone successful balloon angioplasty and had follow-up angiography, 4.9 +/- 4.1 months later. We compared the extent of restenosis between men and women, and between pre- and post-menopausal women, which was assessed by a categorical definition of restenosis (more than 50% diameter stenosis at follow-up) and by percent diameter measured immediately after angioplasty and at follow-up. Hypertension was more frequent in women and a significantly lower percentage of women smoked. In women, the levels of total cholesterol and low-density lipoprotein cholesterol were higher. The location of dilated lesions, frequency of angioplasty for lesions with chronic total occlusion, and frequency of emergency angioplasty in patients with unstable angina or acute myocardial infarction were similar in men and women. Restenosis formation, estimated by the categorical definition or percent diameter, did not differ between men and women, or between pre- and post-menopausal women. Menopausal status or sex was not an independent predictor of restenosis by multivariate analysis. Thus, the benefit of anti-atherogenicity in women does not play an important role in preventing restenosis after coronary angioplasty.     

Coronary-artery stenting compared with balloon angioplasty for restenosis after initial balloon angioplasty. Restenosis Stent Study Group

BACKGROUND: Intracoronary stenting reduces the rate of restenosis after angioplasty in patients with new coronary lesions. We conducted a prospective, randomized, multicenter study to determine whether intracoronary stenting, as compared with standard balloon angioplasty, reduces the recurrence of luminal narrowing in restenotic lesions. METHODS: A total of 383 patients who had undergone at least one balloon angioplasty and who had clinical and angiographic evidence of restenosis after the procedure were randomly assigned to undergo standard balloon angioplasty (192 patients) or intracoronary stenting with a Palmaz-Schatz stent (191 patients). The primary end point was angiographic evidence of restenosis (defined as stenosis of more than 50 percent of the luminal diameter) at six months. The secondary end points were death, Q-wave myocardial infarction, bypass surgery, and revascularization of the target vessel. RESULTS: The rate of restenosis was significantly higher in the angioplasty group than in the stent group (32 percent as compared with 18 percent, P= 0.03). Revascularization of the target vessel at six months was required in 27 percent of the angioplasty group but in only 10 percent of the stent group (P=0.001). This difference resulted from a smaller mean (+/-SD) minimal luminal diameter in the angioplasty group (1.85+/-0.56 mm) than in the stent group (2.04+/-0.66 mm), with a mean difference of 0.19 mm (P=0.01) at follow-up. Subacute thrombosis occurred in 0.6 percent of the angioplasty group and in 3.9 percent of the stent group. The rate of event-free survival at 250 days was 72 percent in the angioplasty group and 84 percent in the stent group (P=0.04). CONCLUSIONS: Elective coronary stenting was effective in the treatment of restenosis after balloon angioplasty. Stenting resulted in a lower rate of recurrent stenosis despite a higher incidence of subacute thrombosis.     

Risk factors for restenosis after balloon angioplasty in focal iliac stenosis

BACKGROUND: The risk factors for restenosis after angioplasty have not yet been established because of the inconsistencies among treated lesions, differences in the techniques used, and variable end points. We evaluated the predictive variables relating to postangioplasty restenosis. METHODS: One hundred sixty-one transluminal balloon angioplasties were studied in 138 consecutive patients with focal iliac arterial stenosis (< or = 4 cm) caused by arteriosclerosis between January 1981 and December 1995. Restenosis was diagnosed on the basis of recurrent symptoms associated with an apparent drop in the ankle-brachial pressure index and angiographic visualization of restenosis. RESULTS: Being younger than 60 years (risk ratio 2.585) and poor runoff (risk ratio 2.328) were found to be important variables predicting restenosis by the Cox regression model. The restenosis-free patency rates were significantly better in patients older than 60 years of age (p = 0.0242), with good distal runoff (p = 0.0487), and without diabetes (p = 0.0111). CONCLUSIONS: Being younger than 60 years of age and poor distal runoff are important predictors of restenosis after iliac balloon angioplasty.     

Endovascular beta-radiation to reduce restenosis after coronary balloon angioplasty: results of the beta energy restenosis trial (BERT)

BACKGROUND: In the porcine overstretch injury model of restenosis, endovascular beta-radiation reduces neointima formation. To determine whether this therapy could be applied to patients with coronary artery disease, a special device was developed to allow delivery of 12 encapsulated 90Sr/Y sources, measuring a total of 30 mm, to various sites within the coronary arterial tree. This study was designed to evaluate the feasibility of the delivery of 12, 14, or 16 Gy at 2 mm after balloon angioplasty of stenoses of native coronary vessels. METHODS AND RESULTS: Delivery of beta-radiation was attempted in 23 patients after successful balloon angioplasty. Source delivery was successful in 21 of the 23 patients (91%). There was no in-hospital or 30-day morbidity or mortality. Follow-up quantitative coronary arteriography in 20 patients demonstrated a late loss of 0.05 mm, a late loss index of 4%, and a restenosis rate of 15%. The use of the beta-emitter 90Sr/Y significantly reduced treatment time and operator exposure compared with previous trials with the gamma-emitter 192Ir. CONCLUSIONS: In this study, the administration of endovascular beta-radiation after angioplasty was safe and feasible and substantially altered the postangioplasty late lumen loss, resulting in a lower-than-expected rate of restenosis. On the basis of these encouraging results, a multicenter, randomized trial with operators and patients blinded to treatment assignment is planned.     

Prolonged dilation improves an unsatisfactory primary result of femoropopliteal artery angioplasty: usefulness of a perfusion balloon catheter

D-[U-14C]Glucosamine was rapidly taken up by oat coleoptile segments and metabolized to radioactive UDP-N-acetylglucosamine, which acted as specific glycosyl donor for the synthesis of glycolipids and cytosolic, membrane-bound and cell-wall glycoproteins. Cell-wall glycoproteins were solubilized from the walls by either cell-wall-degrading enzymes or chemical extractants. The solubilized cell-wall glycoproteins in the presence of peptide N-glycosidase F released oligosaccharide chains higher than seven glycosidic residues. The combined action of peptide N-glycosidase F and N-acetyl-beta-D-glucosaminidase on cell-wall glycoproteins indicated the presence of N-acetylglucosamine residues beta-1,2-linked to mannose. Less than 9% of the radioactive oligosaccharide chains was released from the solubilized cell-wall glycoproteins when treated with 0.5 M NaOH at 20 degrees, whereas more than 45% of the radioactivity was released in the presence of 1 M NaOH at 50 degrees. The high hydrolytic sensitivity of cell-wall glycoproteins to peptide N-glycosidase F, N-acetyl-beta-D-glucosaminidase and NaOH at 50 degrees indicated that most N-acetylglucosamine residues were incorporated into N-linked cell-wall glycoproteins. Further evidence of this was obtained by the use of inhibitors of biosynthesis and processing of N-linked glycoproteins.     

Effects of locally administered argatroban on restenosis after balloon angioplasty: experimental and clinical study

1. This study was undertaken to evaluate the preventive effects of locally administered argatroban, a competitive inhibitor of thrombin-induced platelet activation, on restenosis after balloon angioplasty. 2. A hydrogel-coated balloon catheter was immersed three times in argatroban/saline solution (1 mg/mL) for 60 s, inflated to a pressure of 606 kPa and left in the rabbit common carotid artery for 1 min. The same procedure was performed, without drug, as a control. The pharmacokinetics of delivered argatroban in the arterial wall were assessed using [14C]-argatroban. Platelet deposition 2 h after balloon injury was quantified by fluorescence studies using antiplatelet antibody. Vascular smooth muscle cell (VSMC) proliferation 3 days after balloon injury was assessed by immunohistochemical staining for proliferative cell nuclear antigen (PCNA). In a clinical study, we divided 50 elective patients into two groups: argatroban and control. 3. In the experimental study, the mean quantities of argatroban at 0, 2 and 6 h after deflation were 24.63, 0.49 and 0.11 nmol/g wet weight of artery, respectively. Argatroban was undetected 24 h after deflation. Two hours after deflation, argatroban-treated arteries showed less platelet adhesion than saline-treated controls. The mean number of PCNA-positive cells was 16.9 and 43.8% in the argatroban and control groups, respectively (P < 0.01). In the clinical study, the mean late gain loss was 8.2 and 27.3% in the argatroban and control groups, respectively (P < 0.05). The mean late restenosis rate was 11.1 and 41.4% in the argatroban and control groups, respectively (P < 0.05). 4. These data suggest that blood coagulation plays a significant role in VSMC proliferation after balloon injury and that locally administered argatroban using hydrogel-coated balloon catheter may prevent post-percutaneous transluminal coronary angioplasty restenosis.     

Mechanical debulking versus balloon angioplasty for the treatment of diffuse in-stent restenosis

HeLa cells exposed to cisplatin undergo cell death, presenting morphological and biochemical characteristics typical of apoptosis. In this study we demonstrate that this process is independent of RNA and protein synthesis, since it was not inhibited by actinomycin D or cycloheximide. These substances induced apoptosis by themselves, suggesting an unidentified short-lived inhibitor. The presence of Ca2+ chelators (EDTA and EGTA) did not have effect in this process, excluding the participation of extracellular Ca2+ access. Finally, zinc ions inhibited the low molecular weight DNA degradation and the apoptotic bodies production, but not cell death. These results provide an insight into the mechanism of action of one of the most used antineoplastic drug.     

Coronary restenosis after optimal (stent-like) initial angiographic results obtained by traditional balloon angioplasty

BACKGROUND AND OBJECTIVE: Elective native coronary artery stenting has shown its efficacy in lowering restenosis rates (RR) usually occurring after balloon angioplasty (PTCA). However ability of conventional PTCA to consistently provide low RR, through the achievement of large acute stent-like angiographic results, has not been investigated. This study was conducted to: (1) assess ability of optimal initial dilatation (OID), defined by residual lumen narrowing < or = 20%, significantly reduce current high RR following traditional PTCA; (2) evaluate the efficacy of OID obtainable by conventional PTCA in influencing adverse effects of single variables predisposing to restenosis. METHODS: Of consecutive 601 patients who underwent PTCA, 569 (94.6%), 483 men and 86 women, aged 38-76 years, had a successful procedure on 645/678 lesions (95.1%). After a plaque fracture was obtained by the first inflation, step-increases in pressure of 1 atm and 60 second-inflation-times were applied, until a large lumen (the nearest to normal) and smooth contours were seen, or any wall damage detected by using step-by-step angiographic tests. Acute optimal results (group A) were 450 (69.7%) and sub-optimal results (group B) were 203 (30.3%). After a mean time of 9 +/- 1.8 months, 543 patients (95.4%) had angiographic restudy on 611 (94.7%) successfully treated lesions. RESULTS: Restenosis (> 50% stenosis at restudy) occurred in 27.1% of patients and in 24.5% of lesions. RR was 18.8% in group A and 37.8% in group B (p < 0.0001). Significant lower RR were observed in group A in comparison with group B, for single variables examined, except for length > 10 mm. By multivariate analysis of all treated lesions, sub-optimal initial dilatation, unstable angina, lesion length > 10 mm and eccentricity emerged as major determinants of restenosis. Following OID only length > 10 mm was highly predictive of this event and, in the absence of this adverse variable, RR was only 13.6%. CONCLUSION: Counterbalancing adverse effects of many variables predisposing to restenosis, OID obtained by traditional PTCA seem to significantly reduce the risk of recurrence, particularly in lesions no longer than 10 mm.     

Intravascular ultrasound in determining the end point of percutaneous transluminal coronary angioplasty

Intravascular ultrasound (IVUS) imaging was used to measure internal luminal area immediately after percutaneous transluminal coronary angioplasty (PTCA) in 83 patients (59 males, 24 females, mean age 63 +/- 12 years) with angina pectoris to determine the need for additional intervention. The effectiveness of these interventions to prevent restenosis was also studied. Thirty-five patients (42%) with insufficient dilatation revealed an internal luminal area less than 5 mm2 or luminal stenosis greater than 60% as evaluated by IVUS imaging following the procedure. The luminal area increased from 4.5 +/- 1.1 to 7.9 +/- 2.8 mm2 and the percentage luminal stenosis improved from 66 +/- 9% to 54 +/- 9% in patients who underwent further dilatation with a larger size balloon, longer dilatation time, directional coronary atherectomy, or stenting. The insufficient dilatation group exhibited hard plaque and calcification more frequently than in the other group (48 patients, 58%) in whom sufficient dilatation of the target lesion was achieved. The incidence of restenosis in the sufficient dilatation group was 25%, compared to 33% of the patients receiving additional treatment after IVUS imaging and 42% in the 192 patients who underwent PTCA without IVUS imaging. IVUS imaging is a useful method for evaluation of complex luminal morphology to decrease the incidence of restenosis and for determination of the end point and the extent of dilatation required.     

Balloon angioplasty combined with primary stenting versus balloon angioplasty alone in femoropopliteal obstructions: A comparative randomized study

PURPOSE: The objective of this research is to describe aspects of the organization of adolescent sexual behavior in order to understand factors associated with risk for sexually transmitted diseases (STD). METHODS: Subjects were 82 females (ages 16-19 years; 77% African-American) participating in a larger STD study. Subjects completed diaries for each coital event, recording date of event, partner initial, condom use, and use of drugs or alcohol before intercourse. Partner change was defined as any event for which the sex partner initials differed from those listed for the most recent previous coital event. RESULTS: The 82 subjects recorded 1265 coital events; the average span of the records was 10 weeks. Intercourse was least likely on Sundays (154 of 1265; 12.2%) and most common on Friday and Saturday (221 of 1265 for each day; 17.5%). The proportion of coital events associated with drugs or alcohol increased from Sunday to Saturday, although the proportion of coital events in which a condom was used did not vary significantly. Intercourse was most common in spring and summer, and least frequent in winter. CONCLUSIONS: These data indicate substantial temporal organization of adolescent sexual behaviors that may be related to risk of sexually transmitted diseases. Some STD-preventive interventions may be most effective when targeted to higher risk times.     

Prospects of prevention of restenosis after coronary angioplasty

The prevention of restenosis after coronary angioplasty has been marked over recent years by the failure of trials of drug treatment based on inhibition of arterial smooth muscle cell proliferation. This failure could be due to an insufficient concentration of the orally or intravenously administered drug in the lesion to be treated. Another reason for this failure of drug treatment could be the nonexclusive role of intimal hyperplasia in the pathophysiology of restenosis, which also appears to be related to a education of the overall calibre of the artery at the site of dilatation. The pathogenesis of this phenomenon, called "remodelling", remains obecure and is only partly prevented by insertion of stents, which is currently the only treatment able to decrease the number of new revascularization procedures for restenosis. This benefit is related to optimization of the initial result (stents avoiding early "recoil", secondary to the elastic recoil forces of the arterial wall), and possibly to prevention of late remodelling of the vessel at the site of dilatation, either tonic (vasomotor) or trophic. On the other hand, the benefit related to the absence of "remodelling" of the stended lesions is partly limited by intimal hyperplasia, exacerbated by the presence of the stent. The future therapeutic strategy could combine insertion of stents and prevention of smooth muscle cell proliferation by new treatment strategies acting at the molecular level. Encouraging preliminary results have already been obtained in animals with chimeric toxins, antisense strategies and especially gene therapy using defective adenoviral vectors for replication.     

Serial intravascular ultrasound predictors of restenosis at the margins of Palmaz-Schatz stents

To evaluate predictors of restenosis at margins of Palmaz-Schatz stents, intravascular ultrasound studies were performed after intervention and at follow-up (5.4 months) in 161 stented lesions. Of 301 stent margins, 77 (26%) were restenotic at follow-up (>50% late lumen loss). Intimal hyperplasia was greater for restenotic than for nonrestenotic stents margins. The dominant periprocedural predictor of stent margin restenosis was the plaque burden of the continuous reference segment.     

Arterial remodeling after balloon angioplasty of the coronary artery: an intravascular ultrasound study. PICTURE Investigators. PostTreatment IntraCoronary Transluminal Ultrasound Result Evaluation

OBJECTIVE: Before balloon dilation, failure of compensatory enlargement and even arterial shrinkage are frequently observed at the lesion site in response to plaque accumulation. Balloon angioplasty may be regarded as artificial remodeling to enlarge the artery. The prevalence of the different types of arterial wall remodeling after applied stretch by balloon angioplasty is unknown. METHODS AND RESULTS: In 181 patients an intravascular ultrasound study was performed after coronary balloon angioplasty (n = 200 lesions). The vessel area was measured at a proximal and distal reference site and at the lesion site. Subsequently, the relative vessel area [(Vessel area lesion site)/Vessel area reference site) x 100] was calculated. Lesions were classified in three groups on the basis of their relative vessel areas: > or =105%, <105% but >95%, and < or =95%. A relative vessel area > or =105%, indicating enlargement compared with the reference site, was observed in 84 (44%) lesions. A relative vessel area <105% but >95% was observed in 43 (22%) lesions. A relative vessel area < or =95%, indicating "shrinkage" compared with the reference site, was observed in 66 (34%) lesions. CONCLUSIONS: After balloon angioplasty, the vessel area was found to be smaller compared with the reference site in 34% of the lesions. This small vessel area at the lesion site compared with a reference site may be a reflection of insufficient stretch by balloon angioplasty.     

Potential roles of osteopontin and alphaVbeta3 integrin in the development of coronary artery restenosis after angioplasty

Angioplasty procedures are increasingly used to reestablish blood flow in blocked atherosclerotic coronary arteries. A serious complication of these procedures is reocclusion (restenosis), which occurs in 30-50% of patients. Migration of coronary artery smooth muscle cells (CASMCs) to the site of injury caused by angioplasty and subsequent proliferation are suggested mechanisms of reocclusion. Using both cultured human CASMCs and coronary atherectomy tissues, we studied the roles of osteopontin (OPN) and one of its receptors, alphavbeta3 integrin, in the pathogenesis of coronary restenosis. We also measured the plasma levels of OPN before and after angioplasty and determined the effect of exogenous OPN on CASMC migration, extracellular matrix invasion, and proliferation. We found that cultured CASMCs during log phase of growth and smooth muscle cell layer of the coronary atherosclerotic tissues of patients express both OPN mRNA and protein at a significantly elevated level compared with controls. Interestingly, whereas the baseline plasma OPN levels in control samples were virtually undetectable, those in patient plasma were remarkably high. We also found that interaction of OPN with alphavbeta3 integrin, expressed on CASMCs, causes migration, extracellular matrix invasion, and proliferation. These effects were abolished when OPN or alphavbeta3 integrin gene expression in CASMCs was inhibited by specific antisense S-oligonucleotide treatment or OPN-alphavbeta3 interaction was blocked by treatment of CASMCs with antibodies against OPN or alphavbeta3 integrin. Our results demonstrate that OPN and alphavbeta3 integrin play critical roles in regulating cellular functions deemed essential for restenosis. In addition, these results raise the possibility that transient inhibition of OPN gene expression or blocking of OPN-alphavbeta3 interaction may provide a therapeutic approach to preventing restenosis.     

Pharmacological approaches to the prevention of restenosis after coronary angioplasty

In the absence of distant disease, therapeutic node dissections in malignant melanoma, i.e., dissections of regional nodal basins for palpable suspicious or biopsy-proven positive nodes, offer the chance of cure. The 5-year survival rates after therapeutic lymphadenectomy closely correlate with expected cure rates. Although they varied greatly in the literature, from 19% to 38%, the currently obtainable survival rates are in the upper ranges of this spectrum because patients now are closely followed-up and operated for early palpable nodal disease. Properly done, these procedures carry a low morbidity, but they should be done thoroughly to completely eradicate regional disease and avoid recurrences in the same nodal basin to achieve the maximum survival that is surgically attainable.