HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Figures Only Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Engelke, C. Articles by Belli, A.-M. Search for Related Content PubMed PubMed Citation Articles by Engelke, C. Articles by Belli, A.-M. Social Bookmarking                      What's this?

Using 6-mm Cutting Balloon Angioplasty in Patients with Resistant Peripheral Artery Stenosis: Preliminary Results

¹ Department of Radiology, St. George's Hospital, Blackshaw Rd., London SW17 0QT, United Kingdom.
² Present address: Department of Radiology, Klinikum rechts der Isar, Ismaninger Str. 22, 81675 Munich, Germany.

Received December 12, 2001; accepted after revision February 22, 2002.

 
Address correspondence to C. Engelke.

Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
OBJECTIVE. The objective of this study was to assess the efficacy of 6-mm Cutting Balloon angioplasty in patients with resistant peripheral stenoses caused by neointimal hyperplasia or irradiation-induced arteriopathy in vascular territories that are not amenable for use of the smaller Cutting Balloons that are used in cardiology.

CONCLUSION. Peripheral Cutting Balloon angioplasty with the new 6-mm Cutting Balloon device proved useful in the short term for treatment of peripheral arterial stenoses resistant to conventional angioplasty.

Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Current nonsurgical treatments for peripheral arterial stenoses due to neointimal hyperplasia, fibrosis, or irradiation-induced arteriopathy are suboptimal in many cases. Conventional angioplasty often fails in cases of irradiation-induced stenosis, in-stent restenosis, and bypass graft—associated stenosis [1, 2]. The causes of conventional angioplasty failure include elastic recoil after balloon expansion, which is because of high elasticity of a lesion such as in neointimal hyperplasia, and failure of balloon expansion despite high inflation pressures in rigid strictures because of arterial fibrosis, particularly in irradiation-induced arteriopathy. In the latter situation, stenting also usually fails to overcome the high rigidity of resistant fibrotic strictures.

Of those patients treated successfully with conventional angioplasty for neointimal hyperplasia in peripheral bypass graft stenoses, 44-53% have recurrent stenoses after 1 year [3, 4]. Atherectomy can improve the patency of vessels in these patients to 78-88% at 1-2 years [5,6,7]. However, the use of atherectomy devices as an alternative to peripheral conventional angioplasty is limited because of their relatively large diameter and rigidity and the level of expertise required of the user.

Cutting Balloons (InterVentional Technologies, San Diego, CA) are balloon catheters with longitudinally mounted microsurgical blades. These catheters were designed for the treatment of coronary stenoses that are resistant to conventional balloons. We have used the 4-mm coronary device with success for the treatment of small anastomotic neointimal hyperplasia—induced stenosis in the infrainguinal circulation [8]. A larger 6-mm Cutting Balloon, designed for use in femoral, iliac, and subclavian arteries, has become commercially available. We have used this new peripheral device to improve the treatment of peripheral arterial stenoses resistant to conventional angioplasty in patients who are not amenable to treatment with the smaller cardiology Cutting Balloon because of native vessel or graft diameter. These patients would otherwise have undergone repeated stenting, atherectomy, or surgical procedures at our center.

Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Five patients (three men and two women; 42-76 years old; mean age, 63 years) were prospectively treated at our center between January and October 2001 with Cutting Balloon angioplasty for peripheral arterial stenoses resistant to conventional angioplasty. Each patient gave informed consent before treatment. Our institutional review board does not require its approval for this type of study.

One patient had postirradiation external iliac artery stenosis 8 years after hysterectomy for carcinoma of the cervix and subsequent pelvic radiotherapy (58.3 Gy). One patient had an iliac in-stent restenosis 2 years after repeated iliac stenting for restenosis. Two patients' lesions were anastomotic stenoses of an aortobifemoral polytetrafluoroethylene bypass graft and a femorofemoral crossover polytetrafluoroethylene bypass graft. One patient had an intragraft stenosis of an axillobifemoral polytetrafluoroethylene bypass. All stenoses were short focal lesions 1-3 cm in length. Clinical indications for intervention were severe claudication when walking a short distance (<50 m) (n = 3) and pain at rest (n = 2).

All five patients presented significant stenoses on color duplex sonography. No patient had concomitant stenoses of the arterial inflow or runoff. A significant stenosis was defined on color duplex sonography as a peak systolic velocity (PSV) gradient (ratio) between the stenosis and the normal vessel segment proximal to the stenosis (V = PSV_max/PSV_proximal) of at least 2:5. On angiography, we defined a significant stenosis as a reduction in the vessel diameter by at least 50% using the relation of the minimal intrastenotic vessel diameter to the prestenotic vessel diameter. Patients whose stenoses met both criteria and who had an intraarterial systolic pressure gradient across the lesion of at least 10 mm Hg after intraarterial administration of glyceryl trinitrate were eligible for entry into our study.

The 6-mm (diameter) peripheral Cutting Balloon is a balloon catheter with peripheral vascular specifications that has four longitudinally balloon-mounted microsurgical blades that are exposed during balloon inflation (Fig. 1A,1B). The catheter can be used in combination with 0.021-inch guidewires in an over-the-wire technique. In the peripheral vascular system, 6-mm Cutting Balloon angioplasty is technically analogous to conventional angioplasty. The device requires the use of a 6-French introducer sheath.

View larger version (59K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1A. —Peripheral Cutting Balloon (InterVentional Technologies, San Diego, CA). Photograph of balloon in deflated state shows microtomes (arrows) covered by balloon folds (arrowheads).

View larger version (67K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1B. —Peripheral Cutting Balloon (InterVentional Technologies, San Diego, CA). Photograph of balloon during inflation shows microtomes (black arrows) exposed and pressed into adjacent structures. Balloon expands vessel wall, resulting in directed longitudinal dissection at angioplasty site. This mechanism should minimize wall tension during angioplasty and enable angioplasty of rigid lesions to larger diameter than achieved using conventional angioplasty. Radiopaque markers (white arrows) can be seen through balloon material. Four-leg support (arrowheads) assists in retraction of blades into balloon folds during deflation.

All patients received 150 mg of aspirin the day before intervention. Intraarterial heparin was routinely administered as a 5000-IU bolus after insertion of the 6-French introducer sheath. Intraarterial glyceryl trinitrate in 150-mg doses were injected at the discretion of the operator to prevent arterial spasm and before each intraarterial pressure measurement. After initial diagnostic arteriography was performed, the lesion was crossed using a hydrophilic guidewire (Terumo Europe, Leuven, Belgium) and a 4- or 5-French Cobra catheter (Cordis Europe, Roden, The Netherlands). Conventional angioplasty was first attempted in all patients, using a standard over-the-wire technique with an 0.018-inch guidewire (V18; Boston Scientific International, La Garenne Colombes Cedex, France) and angioplasty balloons having a 6- to 7-mm diameter (Smash; Boston Scientific) with high inflation pressures (12-14 bar).

In all patients, conventional angioplasty was followed by Cutting Balloon angioplasty over the same guidewire. This angioplasty was performed using the Cutting Balloon (diameter, 6 mm; length, 10 mm) with two to three overlapping inflations to cover the entire length of each stenotic lesion. Although the peripheral Cutting Balloon, like the cardiology Cutting Balloon, can be used as a primary angioplasty device, we attempted initial conventional angioplasty in all patients to test the resistance of each lesion. The performance of Cutting Balloon angioplasty in our patients was technically analogous to that of conventional angioplasty using slow balloon inflation. No special centering procedures of the balloon within the vessel lumen were required.

Cutting Balloon angioplasty was followed in four patients by conventional angioplasty to a 6- to 7-mm diameter to restore normal arterial gauge. In each patient, the balloon size that we used for conventional angioplasty was identical before and after Cutting Balloon angioplasty. As a control, digital subtraction angiography was performed after each conventional and Cutting Balloon angioplasty procedure. We measured the systolic arterial pressure gradient across the lesion after injection of a 150-mg bolus of glyceryl trinitrate. The final angiogram showed the Cutting Balloon angioplasty site and runoff vessels for assessment of potential complications such as dissection, occlusion, or distal embolization. Four of the five patients had arterial access from the ipsilateral side; one patient with aortobifemoral graft and stenosis at the profunda femoris artery anastomosis underwent crossover Cutting Balloon angioplasty.

Technical success was defined as improvement in luminal diameter to a residual stenosis equal to or less than 20% and a residual systolic arterial pressure gradient across the lesion of less than 10 mm Hg. Restenosis was defined as a stenosis greater than 50% on angiography or a PSV gradient on color duplex sonography greater than or equal to 2.5. Clinical success was defined as the complete relief or substantial improvement of symptoms. Follow-up in all patients included clinical evaluation and color duplex sonography at 6 weeks after the intervention and repeated at 3-month intervals.

Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Handling of the Cutting Balloons was straightforward in all lesions. No patients presented special requirements for arterial access as a result of the vascular anatomy or the profile and flexibility of the Cutting Balloon catheters. All lesions were easily accessible over the 0.018-inch guidewire. Conventional angioplasty failed to achieve an angiographically acceptable result (Fig. 2A,2B,2C,2D,2E) in all lesions. In distinction, Cutting Balloon angioplasty was technically successful in all five patients. The Cutting Balloons expanded completely, and no balloon waist remained. All lesions were dilated with a good angiographic result and without technical or clinical complications (Figs. 2A,2B,2C,2D,2E and 3A,3B,3C,3D). Removal of the Cutting Balloon device through the introducer sheath was straightforward in all patients. The technical success of Cutting Balloon angioplasty was significantly better than that of conventional angioplasty (p = 0.001; 95% CI = 35.23-78.77, Fisher's exact test).

View larger version (95K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2A. —42-year-old woman 8 years after hysterectomy for carcinoma of cervix and subsequent pelvic radiotherapy (58.3 Gy) with new onset of pain in right leg while at rest. Digital subtraction angiogram reveals focal stenosis (arrowhead) of right proximal external iliac artery consistent with irradiation-induced stenosis with intra arterial systolic pressure gradient of 40 mm Hg before intervention.

View larger version (90K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2B. —42-year-old woman 8 years after hysterectomy for carcinoma of cervix and subsequent pelvic radiotherapy (58.3 Gy) with new onset of pain in right leg while at rest. Unsubtracted image shows persisting balloon waist (arrowhead), indicating resistance to conventional angioplasty with 7 x 4 cm angioplasty balloon (Smash; Boston Scientific International, La Garenne Colombes, France) at inflation pressure of 14 atm.

View larger version (92K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2C. —42-year-old woman 8 years after hysterectomy for carcinoma of cervix and subsequent pelvic radiotherapy (58.3 Gy) with new onset of pain in right leg while at rest. Digital subtraction angiogram immediately after attempted conventional angioplasty reveals residual stenosis (arrowhead) that had 35 mm Hg systolic pressure gradient on intraarterial pressure assessment.

View larger version (115K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2D. —42-year-old woman 8 years after hysterectomy for carcinoma of cervix and subsequent pelvic radiotherapy (58.3 Gy) with new onset of pain in right leg while at rest. Unsubtracted image shows response to Cutting Balloon (InterVentional Technologies, San Diego, CA) angioplasty with full expansion of device (arrowhead) at 8 atm.

View larger version (83K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2E. —42-year-old woman 8 years after hysterectomy for carcinoma of cervix and subsequent pelvic radiotherapy (58.3 Gy) with new onset of pain in right leg while at rest. Digital substraction angiogram after Cutting Balloon angioplasty shows angioplasty site (arrowheads) has no residual stenosis. Intraarterial pressure assessment showed no systolic pressure gradient. In this patient, Cutting Balloon angioplasty was not followed by conventional angioplasty.

View larger version (99K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3A. —67-year-old man with claudication at 20 m, 3 years after stenting from common to external iliac artery (balloon expandable 8-mm stainless steel, Bridge X3: Medtronic, Santa Rosa, CA). Digital subtraction angiogram reveals in-stent restenosis (arrowhead) with 40 mm Hg intraarterial systolic pressure gradient.

View larger version (103K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3B. —67-year-old man with claudication at 20 m, 3 years after stenting from common to external iliac artery (balloon expandable 8-mm stainless steel, Bridge X3: Medtronic, Santa Rosa, CA). Digital subtraction angiogram shows significant residual stenosis (arrowheads). After attempted conventional angioplasty with 7 x 4 cm balloon (Smash; Boston Scientific International, La Garenne Colombes, France) using inflation pressure of 14 atm, systolic pressure gradient (40 mm Hg) was unchanged.

View larger version (87K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3C. —67-year-old man with claudication at 20 m, 3 years after stenting from common to external iliac artery (balloon expandable 8-mm stainless steel, Bridge X3: Medtronic, Santa Rosa, CA). Digital subtraction angiogram shows minimal residual stenosis (arrowhead) with residual systolic pressure gradient of 6 mm Hg after Cutting Balloon (InterVentional Technologies, San Diego, CA) angioplasty with inflation pressure of 8 atm.

View larger version (75K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3D. —67-year-old man with claudication at 20 m, 3 years after stenting from common to external iliac artery (balloon expandable 8-mm stainless steel, Bridge X3: Medtronic, Santa Rosa, CA). Digital subtraction angiogram shows unremarkable appearance of angioplasty site (arrowhead) after subsequent conventional angioplasty using same size (7 x 4 cm) conventional angioplasty balloon. Intraarterial pressure assessment confirmed unchanged systolic gradient of 6 mm Hg.

Initial conventional angioplasty failed in all patients with only minimal improvement of stenosis on angiography and hemodynamic pressure measurements. Cutting Balloon angioplasty decreased the degree of stenosis to below significance in all patients (Table 1). This finding correlated well with the color duplex sonography results (mean PSV — gradient before intervention = 2.86 [range, 2.5 to > 4]; all PSV gradients after intervention < 2). To date (follow-up range, 4-9 months; mean, 6.4 months), no local restenoses or occlusions have occurred. All patients responded clinically to the treatment. No patient had recurrent clinical ischemia.

Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
The concept of using balloon-mounted surgical microtomes to enhance conventional angioplasty was introduced by Barath et al. [9]. The Cutting Balloon is designed for the percutaneous treatment of stenoses of the peripheral artery that are resistant to treatment because of neointimal hyperplasia or fibrosis. Because it has a relatively low profile and a high level of flexibility, the Cutting Balloon has major handling advantages compared with atherectomy devices and balloon-expandable stent systems. The three to four longitudinally balloon-mounted microsurgical blades cut directly into the stenotic lesion during balloon inflation. These microincisions disrupt the fibroelastic continuity of neointimal hyperplasia and fibrotic tissue and thereby minimize the elastic recoil, enabling dilatation to a larger diameter than could be achieved by stand-alone conventional angioplasty [10].

Cutting Balloon angioplasty has been used for the treatment of coronary in-stent restenosis as a coronary model for neointimal hyperplasia [11]. In a retrospective analysis of in-stent restenosis that compared Cutting Balloon angioplasty, conventional angioplasty, and atherectomy, Adamian et al. [12] found that Cutting Balloon angioplasty had the most favorable outcome (6-month restenosis rates of 25%, 43%, and 34%, respectively). Hence, in complex coronary artery lesions resistant to conventional coronary balloon angioplasty, Cutting Balloon angioplasty offers a reasonable alternative to atherectomy [12].

At our center, we do not use high-pressure (burst pressure, 20 atm) balloon angioplasty for patients with neointimal hyperplasia to test the rigidity of the stenosis and exceed standard pressure in an attempt to achieve a technically acceptable result. Therefore, the burst pressure of a conventional balloon is the definition of failure at our center. We are evaluating whether neointimal hyperplasia of peripheral bypass graft stenosis or in-stent restenosis and irradiation-induced arteriopathy—as different pathologic entities from atherosclerotic strictures—require mechanical treatments other than conventional angioplasty. Such improvement of mechanical treatments is particularly important because experimental therapies for prophylaxis of neointimal hyperplasia, including gene or radiation therapy, are cumbersome and may only delay the onset of restenosis; these therapies are unlikely to enter clinical practice in the near future, if at all [2].

In peripheral artery lesions that are resistant to conventional angioplasty, using stenting and atherectomy can result in reasonable short-term results [2, 5,6,7]. However, repeated stenting of in-stent restenosis overexpands the arterial wall.

Very rigid intimal lesions and fibrosis do not often respond to high conventional angioplasty pressures (12-14 bar) or repeated stenting [2]. Furthermore, the durability of stents placed below the inguinal ligament is disappointing and precludes their use in distal graft anastomotic strictures. The use of peripheral atherectomy devices is limited by their relatively large bore and their rigidity.

Experience in the use of Cutting Balloon angioplasty in the noncoronary circulation has been limited to the treatment of resistant stenoses in hemodialysis fistulas and grafts [13], in pediatric pulmonary artery branch stenosis [14], and in small anastomoses in peripheral arterial bypass grafts [8]. There is, as well, a single reported case regarding renal artery in-stent restenosis [15]. Complications of Cutting Balloon angioplasty, to our knowledge, are limited to one coronary artery aneurysm after coronary artery angioplasty and focal coronary artery dissections [16, 17].

The advent of the 6-mm peripheral device widens the spectrum of potential Cutting Balloon angioplasty applications to the salvage of larger bypass grafts, in-stent restenosis in renal and iliac arteries, and irradiation arteriopathy or fibrosis in iliac and extremity arteries. Our small series shows a new versatility in classic peripheral artery target vessels above the inguinal ligament or in larger bypass grafts (7-9 mm diameter), and our findings add the peripheral Cutting Balloon to the potential endovascular arsenal for difficult-to-treat neointimal hyperplasia—related stenoses and other resistant peripheral artery stenoses. Our short-term results are promising but preliminary: peripheral Cutting Balloon angioplasty merits further evaluation in larger studies in comparison with the competing endovascular techniques.

Acknowledgments
 
We thank J. Martin Bland from our Department of Medical Statistics for his invaluable advice and help.

References

Top Abstract Introduction Subjects and Methods Results Discussion References

 

1. Cormier F, Korso F, Fichelle JM, Gautier C, Cormier JM. Post-irradiation axillo-subclavian arteriopathy: surgical revascularization [in French]. J Mal Vasc 2001;26:45 -49[Medline]
2. Di Mario C, Marsico F, Adamian M, Karvouni E, Albiero R, Colombo A. New recipes for in-stent restenosis: cut, grate, roast or sandwich the neointima? Heart 2000;84:471 -475[Free Full Text]
3. Hoksbergen AW, Legemate DA, Reekers JA, Ubbink DT, Jacobs MJ. Percutaneous transluminal angioplasty of peripheral bypass stenoses. Cardiovasc Intervent Radiol 1999;22:282 -286[Medline]
4. Spijkerboer AM, Beek FJ, Graaf Y, Eikelboom BC, Mali WP. The predictive value of angiographic results for the outcome of percutaneous transluminal angioplasty in stenosed femoral bypass grafts. Cardiovasc Intervent Radiol 1997;20:98 -102[Medline]
5. Porter DH, Rosen MP, Skillman JJ, Sheiman RG, Kent KC, Kim D. Mid-term and long-term results with directional atherectomy of vein graft stenoses. J Vasc Surg 1996;23:554 -567[Medline]
6. Vinnicombe SJ, Heenan SD, Belli AM, Buckenham TM. Directional atherectomy in the treatment of anastomotic neointimal hyperplasia associated with prosthetic arterial grafts: technique and preliminary results. Clin Radiol 1994;49:773 -778[Medline]
7. Dolmatch BL, Gray RJ, Horton KM, Rundback JH, Kline ME. Treatment of anastomotic bypass graft stenosis with directional atherectomy: short-term and intermediate-term results. J Vasc Interv Radiol 1995;6:105 -113[Medline]
8. Engelke C, Morgan RA, Belli AM. Cutting balloon percutaneous transluminal angioplasty for salvage of lower limb arterial bypass grafts: feasibility. Radiology 2002;223:106 -114[Abstract/Free Full Text]
9. Barath P, Fishbein MC, Vari S, Forrester JS. Cutting balloon: a novel approach to percutaneous angioplasty. Am J Cardiol 1991;68:1249 -1252[Medline]
10. Muramatsu T, Tsukahara R, Ho M, et al. Efficacy of cutting balloon angioplasty for lesions at the ostium of the coronary arteries. J Invasive Cardiol 1999;11:201 -206[Medline]
11. Freitas JO Jr, Berti SL, Bonfa JG, Speranza MS, Gandolphi PP, Bongiovani HL. Cutting balloon angioplasty for intrastent restenosis treatment. Arq Bras Cardiol 1999;72:615 -620[Medline]
12. Adamian M, Colombo A, Briguori C, et al. Cutting balloon angioplasty for the treatment of in-stent restenosis: a matched comparison with rotational atherectomy, additional stent implantation and balloon angioplasty. J Am Coll Cardiol 2001;38:672 -679[Abstract/Free Full Text]
13. Vorwerk D, Adam G, Muller-Leisse C, Guenther RW. Haemodialysis fistulas and grafts: use of cutting balloon to dilate venous stenoses. Radiology 1996;201:864 -867[Abstract/Free Full Text]
14. Schneider MB, Zartner PA, Magee AG. Images in cardiology: cutting balloon for treatment of severe peripheral pulmonary stenosis in a child. Heart 1999;82:108 -108[Free Full Text]
15. Munneke GJ, Engelke C, Morgan RA, Belli AM. Cutting balloon angioplasty for resistant renal artery in-stent restenosis. J Vasc Interv Radiol 2002;13:327 -331[Medline]
16. Bertrand OF, Mongrain R, Soualmi L, et al. Development of coronary aneurysm after cutting balloon angioplasty: assessment by intracoronary ultrasound. Cathet Cardiovasc Diagn 1998;44:449 -452[Medline]
17. Marti V, Martin V, Garcia J, Guiteras P, Auge JM. Significance of angiographic coronary dissection after cutting balloon angioplasty. Am J Cardiol 1998;81:1349 -1352[Medline]

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				P. Dick, S. Sabeti, W. Mlekusch, O. Schlager, J. Amighi, M. Haumer, M. Cejna, E. Minar, and M. Schillinger Conventional Balloon Angioplasty versus Peripheral Cutting Balloon Angioplasty for Treatment of Femoropopliteal Artery In-Stent Restenosis: Initial Experience Radiology, July 1, 2008; 248(1): 297 - 302. [Abstract] [Full Text] [PDF]

				J. Amighi, M. Schillinger, P. Dick, O. Schlager, S. Sabeti, W. Mlekusch, M. Haumer, R. Mathies, G. Heinzle, A. Schuster, et al. De Novo Superficial Femoropopliteal Artery Lesions: Peripheral Cutting Balloon Angioplasty and Restenosis Rates--Randomized Controlled Trial Radiology, April 1, 2008; 247(1): 267 - 272. [Abstract] [Full Text] [PDF]

This Article Abstract Figures Only Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Engelke, C. Articles by Belli, A.-M. Search for Related Content PubMed PubMed Citation Articles by Engelke, C. Articles by Belli, A.-M. Social Bookmarking                      What's this?