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Czytanie potrzebuje wsparcia. Trzeba je promować, jednak nie poprzez akcje, które docierają jedynie do czytających, a przy tym są jednorazowe, obliczone na wysoki zysk w krótkim czasie. Czytanie to proces, i właśnie na procesie powinny opierać się kampanie społeczne i interakcje związane z zaproszeniem do świata książki.

On the basis of a comparative analysis of the worlds presented in Moscoviada by Yurii Andrukhovych and in the Little Apocalypse by Tadeusz Konwicki the article demonstrates the meaning of "metaphorical translation". Using the category proposed by Joseph Brodsky, the author of the article shows how similar characters, who search for their identities, are presented in both books.

Pociąg linii M to trzecia książka Patti Smith, która trafia do rąk polskich czytelników. Po wprowadzających w świat nowojorskich beatników Poniedziałkowych dzieciach oraz zbiorze miniatur Obłokobujanie otrzymujemy pozycję, którą można uznać za klaser lektur i wspomnień jednej z największych żyjących artystek rockowych.

Rafała Wojaczka określa się w polskim literaturoznawstwie mianem poety przeklętego, podobną etykietę przypina się amerykańskiej poetce Anne Sexton. Oboje podejmują w swojej twórczości próby autoanalizy, piszą o ciele, tworząc swoistą formułę „pisania sobą”. Proponowany temat będzie próbą porównania wykreowanego podmiotu cierpiącego w liryce amerykańskiej poetki Anne Sexton i polskiego poety Rafała Wojaczka. Wychodzimy z założenia, że podmiot poezji wymienionych twórców ukonstytuowały kategorie takie jak choroba, ból, cierpienie, które obecne są w ich poezji, chociaż w sposób odmienny. Szczególnie interesować nas będą podobieństwa i różnice poetyckich reprezentacji ciała samobójców. Skupimy się na utworach, które pozwolą opisać nam za pomocą fragmentów poetyckich Sexton i Wojaczka uniwersalne doświadczenia homo patiens.

The article presented the interaction between Ukrainian and Polish writers, who were living in Cracow at the turn ol the 20th centurv. Cracow in the late 19dl and early 20th century was a city in which resided a large group of Ukrainian poets, writers and artists, who constituted themselves as a group of the literary Moloda Muza. This artistic movement developed under the influence of the ideals of the Młoda Polska and personal contacts with Cracow artists (including friendship of Stanislaw Przvbvszewski with Wasyl Stefanyk). Many of the artists associated with the Mloda Muza were guests of the Ukrainian professor at the Jagiellonian University, Bohdan Lepki. Among the Ukrainian Impressionist artists who worked or stayed in Cracow at the beginning of the 2011' century one mav mention the novelist Wasvl Stefanvk (he studied medicine in Cracow). Stefanvk wrote short stories, which were translated into Polish, analyzed and popularized by Cracow’s writers, critics, scholars and publishers, his texts were published in "Życie", "Czas Krakowski", "Świat Słowiański". A special role is played by his contacts with Władysław Orkan, who explained him to his contemporary Ukrainian writers and released two particularly important collections - Młoda Ukraina (1908) and the Antologia współczesnych poetów ukraińskich (1910).

The current study was designed to test the hypothesis that intramuscular (i.m.) injection of naked DNA leads to distribution of the injectate remote from the site of needle placement, a finding that might be expected to facilitate i.m. gene transfer. Transcutaneous ultrasound imaging was employed to monitor online the extent to which a solution of phVEGF165 was distributed among the skeletal musculature during 288 i.m. injections in 18 consecutive patients. In 237 (82.3%) of 288 muscle sites, the injection was performed into the distal calf muscle. In 51 (17.7%) of 288 muscle sites, injection was performed into the first and/or second interosseous muscles of the dorsal foot. Unperturbed muscle was recognized by a characteristic echogenic, stippled texture that was bounded by more intensely echogenic fascia. When i.m. gene transfer was performed into the calf muscles, the injectate was distributed along a longitudinal dimension of 3.59 +/- 0.79 cm (1.39-5.87 cm); the corresponding area of injectate measured by on-line planimetry was 1.83 +/- 0.51 cm2 (0.62-3.41 cm2). When i.m. gene transfer was performed into the interosseous muscles of the foot, the longitudinal extent of injectate distribution was 2.49 +/- 0.66 cm (1.61-3.91 cm), with a corresponding injectate area of 1.71 +/- 0.54 cm2 (0.51-2.86 cm2). These findings establish that a solution of plasmid DNA administered by direct i.m. injection into the skeletal muscles of the limb is distributed well beyond the site of needle entry. Thus, the use of multiple injections performed at different sites is likely to result in broad distribution of DNA injectate, a physical factor that may act to facilitate naked DNA and/or other gene transfer strategies.

Abstract —Preclinical studies in animal models and early results of clinical trials in patients suggest that intramuscular injection of naked plasmid DNA encoding vascular endothelial growth factor (VEGF) can promote neovascularization of ischemic tissues. Such neovascularization has been attributed exclusively to sprout formation of endothelial cells derived from preexisting vessels. We investigated the hypothesis that VEGF gene transfer may also augment the population of circulating endothelial progenitor cells (EPCs). In patients with critical limb ischemia receiving VEGF gene transfer, gene expression was documented by a transient increase in plasma levels of VEGF. A culture assay documented a significant increase in EPCs (219%, P P P v β 3 , and E-selectin after VEGF gene transfer. Constitutive overexpression of VEGF in patients with limb ischemia augments the population of circulating EPCs. These findings support the notion that neovascularization of human ischemic tissues after angiogenic growth factor therapy is not limited to angiogenesis but involves circulating endothelial precursors that may home to ischemic foci and differentiate in situ through a process of vasculogenesis.

Background Clinical studies have suggested that smooth muscle cell (SMC) hyperplasia is the most likely cause of in-stent restenosis. However, pathological data regarding this issue are limited. Specifically, direct evidence of proliferative activity in tissues excised from stenotic stents has not been previously reported. Methods and Results Tissue specimens were retrieved by directional atherectomy from 10 patients in whom in-stent restenosis complicated percutaneous revascularization of peripheral artery disease. Analysis of cellular composition was performed quantitatively after cell-specific immunostaining. For specimens preserved in methanol (7 of 10), cellular proliferation was evaluated by use of antibodies to proliferating cell nuclear antigen (PCNA), cyclin E, and cdk2. TUNEL staining for apoptosis was performed on 8 paraformaldehyde-preserved specimens. Each of the 10 specimens contained extensive foci of hypercellularity composed predominantly of SMCs (mean±SEM, 59.3±3.0%). Evidence of ongoing proliferative activity was documented in all 7 methanol-preserved specimens: 24.6±2.3% of SMCs were PCNA-positive, 24.8±3.1% were cyclin E–positive, and 22.5±2.2% were cdk2-positive. Apoptotic cells were detected in all 8 specimens that had been appropriately preserved to permit DNA nick-end labeling. Macrophages and leukocytes were identified in each of the 10 specimens but accounted for a proportionately smaller number of cells (14.5±1.9% and 9.5±1.4%, respectively). Organized thrombus was observed in 6 of the 10 specimens. Conclusions These findings support the notion that in-stent restenosis results from SMC hyperplasia and suggest that adjunctive therapies designed to inhibit SMC proliferation may further enhance the utility of endovascular stents.

The age-adjusted prevalence of peripheral arterial disease (PAD) in the U.S. population has been estimated to approach 12%. The clinical consequences of occlusive peripheral arterial disease (PAD) include pain on walking (claudication), pain at rest, and loss of tissue integrity in the distal limbs; the latter may ultimately lead to amputation of a portion of the lower extremity. Surgical bypass techniques and percutaneous catheter-based interventions may be used to successfully revascularize the limbs of certain patients with PAD. In many patients, however, the anatomic extent and distribution of arterial occlusion is too severe to permit relief of pain and/or healing of ischemic ulcers. No effective medical therapy is available for the treatment of such patients. The purpose of this clinical protocol is to document the safety of therapeutic angiogenesis achieved in this case by percutaneous catheter-based delivery of the gene encoding vascular endothelial growth factor (VEGF) in patients with P...

Scientific Abstract “Restenosis” is the term which has been used to denote recurrent narrowing of a blood vessel after an initially successful revascularization procedure, such as percutaneous tran...

Peripheral Artery Disease: Primary Pharmacological Therapy Is Ineffective for Patients With Critical Limb Ischemia The prognosis for patients with chronic critical leg ischemia, ie, rest pain and/or established lesions that jeopardize the integrity of the lower limbs, is often poor. Psychological testing of such patients has typically disclosed quality-of-life indexes similar to those of patients with cancer in critical or even terminal phases of their illness.1 It has been estimated that in toto,2 150 000 patients per year require lower-limb amputations for ischemic disease in the United States. Their prognosis after amputation is even worse3 : the perioperative mortality for below-knee amputation in most series is 5% to 10% and for above-knee amputation 15% to 20%. Even when they survive, nearly 40% will have died within 2 years of their first major amputation; a major amputation is required in 30% of cases; and full mobility is achieved in only 50% of below-knee and 25% of above-knee amputees. These grim statistics are compounded by the lack of efficacious drug therapy. As concluded in the Consensus Document of the European Working Group on Critical Leg Ischemia,3 “. . .there presently is inadequate evidence from published studies to support the routine use of primary pharmacological treatment in patients with critical leg ischemia. . . .” Evidence for the utility of medical therapy in the treatment of claudication is no better.4 5 Consequently, the need for alternative treatment strategies in such patients is compelling. ### Therapeutic Angiogenesis Is a Novel Strategy for the Treatment of Critical Limb Ischemia The therapeutic implications of angiogenic growth factors were identified by the pioneering work of Folkman6 and other workers more than two decades ago. Beginning a little more than a decade ago,7 a series of polypeptide growth factors were purified, sequenced, and demonstrated to be responsible for natural as well as pathological angiogenesis. More recent investigations have established the feasibility of using recombinant formulations of such angiogenic growth …

BACKGROUND Previous postmortem studies have demonstrated compensatory enlargement of atherosclerotic arteries in animal models and patients. Conclusions regarding these changes were drawn based on a comparison of the dimensions of diseased arteries in one group of subjects with the dimensions of normal arteries in another group. This method admits potential confounding variables, such as demographics and other disease states, which might also have an impact on arterial size. METHODS AND RESULTS Using intravascular ultrasound, we studied a total of 62 paired, adjacent normal and diseased sites in the superficial femoral arteries of 20 patients undergoing peripheral vascular interventions. Morphological assessment was performed using a computer-based image analysis system. Measurements were made of the cross-sectional area of the arterial lumen, the atherosclerotic plaque, and the outer border of the artery. These dimensions were then compared to determine the effects of progressive atherosclerosis on arterial morphology. Luminal cross-sectional area decreased from 21.1 +/- 2.2 mm2 in normal segments to 16.7 +/- 0.8 mm2 (P = .0001) in adjacent atherosclerotic segments. Similarly, minimal luminal diameter decreased from 5.7 +/- 0.2 to 5.0 +/- 0.1 mm2, and maximal luminal diameter decreased from 6.2 +/- 0.2 to 5.7 +/- 0.2 mm2. At these same sites, total arterial area was 32.9 +/- 1.6 and 37.9 +/- 1.9 mm2 (P = .0001) in normal and diseased segments, respectively. Minimal and maximal arterial diameters demonstrated similar increases (7.3 +/- 0.2 to 7.7 +/- 0.2 mm2 [P = .0015] and 7.6 +/- 0.2 to 8.3 +/- 0.2 mm2 [P = .0001], respectively). Regression analysis disclosed correlation of the cross-sectional area of plaque to the total arterial area (R = .70, P = .0001). CONCLUSIONS Human arteries enlarge in response to progressive atherosclerosis. This compensatory mechanism results in an increase in arterial size that is proportionate to the cross-sectional area of plaque that has accumulated in the vessel. Intravascular ultrasound demonstrates that this process is focal compensatory enlargement at discrete sites of atherosclerotic narrowing immediately adjacent to more normal areas in which arterial size is smaller.

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. The areas of the arterial wall, plaque, lumen, and areas resulting from angioplasty-induced plaque fractures were measured immediately after angioplasty in vivo and compared with findings recorded immediately before angioplasty. Angioplasty increased luminal cross-sectional area (CSA) from 11.5 +/- 0.6 mm2 before angioplasty to 25.4 +/- 1.2 mm2 after angioplasty (p = 0.0001). CSA of the portion of the postangioplasty neolumen contained within angioplasty-induced plaque fractures measured 10.0 +/- 0.8 mm2; the neolumen excluding the area contributed by these plaque fractures measured 15.4 +/- 0.8 mm2. Thus, the area contained within plaque fractures accounted for 10.0 mm2 (71.9%) of the 13.9-mm2 increase in luminal CSA after angioplasty. Analysis of CSA occupied by atherosclerotic plaque disclosed that plaque CSA decreased from 33.8 +/- 1.8 mm2 before angioplasty to 22.5 +/- 1.5 mm2 after angioplasty (p = 0.0001). Plaque CSA was thus reduced ("compressed") by 11.3 +/- 1.1 mm2. Total artery CSA increased ("stretched") slightly from 45.3 +/- 2.6 mm2 before angioplasty to 47.8 +/- 2.0 mm2 after angioplasty (p = 0.0025). CONCLUSIONS In vivo analysis of iliac stenoses by intravascular ultrasound immediately before and after angioplasty demonstrates that plaque fractures and "compression" of atherosclerotic plaque are the principal factors responsible for increased luminal patency resulting from balloon angioplasty. "Stretching" of the arterial wall provides an additional, but minor, contribution.

BACKGROUND The pathological consequences of cardiovascular laser irradiation have been studied extensively in vitro. Previous in vivo studies of laser-induced injury have included analyses of acute and/or chronic findings in experimental animals. Little information, however, is available regarding the acute effects of laser irradiation of human vascular tissues in vivo. METHODS AND RESULTS To determine the acute pathology resulting from laser irradiation of human vascular tissue in vivo, specimens retrieved from 23 patients by directional atherectomy immediately after laser angioplasty (19 peripheral and four coronary) were examined by light microscopy. Of the 23 patients, three (13.0%) were treated with a metal-capped ("hot-tip") fiber coupled to a continuous-wave neodymium:yttrium-aluminum-garnet (Nd:YAG) laser using up to 18 W power and 18-305 seconds of cumulative exposure time; in all three patients (100%), thermal injury, including frank charring several cell layers thick, was seen along the luminal borders of the atherectomy specimen. In eight of the 23 patients (34.5%), laser angioplasty was performed using a 250-microseconds holmium:YAG laser at fluences up to 2,300 mJ/mm2, a repetition rate of 5 Hz, and 25-200 seconds of cumulative exposure; in seven of eight patients (85.5%), the atherectomy specimen showed signs of vacuolar injury consisting of central and satellite Alcian-blue-negative vacuoles. In two patients (25.0%), there was a "smudged" or "shredded" edge, whereas in one patient, frank signs of thermal injury were observed. Finally, in 12 of the 23 patients (52.2%), laser angioplasty was performed using a 120-nsec excimer laser at fluences up to 60 mJ/mm2, a repetition rate of 25 Hz, and a cumulative exposure time of 21-315 seconds. Pathological findings among these 12 patients were limited to nine patients (75%) in whom a weakly basophilic, smudged, and/or shredded appearance approximately one cell layer thick was observed along the luminal border of the atherectomy specimen and two patients (16.7%) with small foci of vacuolar injury. None of the atherectomy specimens retrieved after excimer laser angioplasty disclosed signs of thermal injury. CONCLUSIONS These findings document that acute pathological alterations resulting from in vivo laser angioplasty are variable, depending on the laser source used, and are similar to that predicted by experimental studies performed previously in vitro. The prognostic implications of these varying pathological features remain to be clarified.

Objective Randomized, blinded trial of intramuscular gene transfer using plasmid vascular endothelial growth factor (VEGF) to treat diabetic polyneuropathy. Methods Diabetic patients with polyneuropathy were randomized to receive a VEGF-to-placebo ratio of 3:1. Three sets of injections were given at eight standardized sites adjacent to the sciatic, peroneal, and tibial nerves of one leg. Primary outcomes were change in symptom score at 6 months and a prespecified overall clinical and electrophysiological improvement score. Secondary outcomes were differences in symptoms, examination scores, visual analog pain scale, nerve conduction, and quantitative sensory testing. Results Thirty-nine patients received plasmid VEGF and 11 received placebo. Mean symptom score improved in both legs at 6 months, favoring VEGF over placebo (−1.2 ± 0.5 vs −0.9 ± 0.5; p < 0.01 after adjustment for change in the untreated leg) and compared with the untreated leg (−0.7 ± 0.5; p = 0.02). The region of sensory loss and visual analog pain scale improved in the treated group (−1.5 vs −0.5; p = 0.01). Twelve of 39 VEGF versus 2 of 11 placebo patients met criterion for overall improvement. Other measures including nerve conduction potentials did not improve. There were 84 adverse events in VEGF patients, and 22 were serious; there were 51 events in placebo patients, and 2 were serious. Interpretation Intramuscular plasmid VEGF gene transfer improved diabetic neuropathic symptoms, meeting primary end-point criteria for efficacy but not affecting most secondary measures. Treatment was associated with more serious adverse events that did not reach statistical significance. These results are not conclusive but may justify further clinical study. Ann Neurol 2009;65:386–393

Background— Critical limb ischemia, a manifestation of severe peripheral atherosclerosis and compromised lower-extremity blood flow, results in a high rate of limb loss. We hypothesized that adenoviral delivery of a constitutively active form of the transcription factor hypoxia-inducible factor-1α (ie, Ad2/HIF-1α/VP16 or HIF-1α) into the lower extremity of patients with critical limb ischemia would be safe and might result in a durable clinical response. Methods and Results— This phase I dose-escalation program included 2 studies: a randomized, double-blind, placebo-controlled study and an open-label extension study. In total, 34 no-option patients with critical limb ischemia received HIF-1α at doses of 1×10 8 to 2×10 11 viral particles. No serious adverse events were attributable to study treatment. Five deaths occurred: 3 in HIF-1α and 2 in placebo patients. In the first (randomized) study, 7 of 21 HIF-1α patients met treatment failure criteria and had major amputations. Three of the 7 placebo patients rolled over to receive HIF-1α in the extension study. No amputations occurred in the 2 highest-dose groups of Ad2/HIF-1α/VP16 (1×10 11 and 2×10 11 viral particles). The most common adverse events included peripheral edema, disease progression, and peripheral ischemia. At 1 year, limb status observations in HIF-1α patients included complete rest pain resolution in 14 of 32 patients and complete ulcer healing in 5 of 18 patients. Conclusions— HIF-1α therapy in patients with critical limb ischemia was well tolerated, supporting further, larger, randomized efficacy trials.

To investigate the effects of vascular endothelial growth factor gene therapy on ischemic neuropathy in patients with critical limb ischemia.An open-label, dose-escalating trial. Patients with angiographically proven critical leg ischemia received injections of phVEGF(165) human plasmid in the muscles of the ischemic limb. Testing before treatment and at 3 and 6 months included (1) symptom severity score, (2) clinical examination score, and (3) electrophysiologic studies. Clinical and electrophysiologic examiners were masked to each other's findings.A tertiary care referral hospital and a major teaching affiliate of Tufts University School of Medicine, Boston, Mass.Of 29 consecutive patients enrolled, 17 (19 limbs) completed the 6 months of study. Six patients had diabetes. Compared with baseline studies, treated patients had significant clinical improvements in the symptom score (P.01), sensory examination score (P.01), total examination score (P =.01), peroneal motor amplitude (P =.03), and quantitative vibration threshold (P =.04). Improvement in the vascular ankle-brachial index in treated legs (P.01) corresponded to improvement in neuropathy in the same limb. Neurologic improvement was seen in 4 of 6 patients with diabetes who completed the study. No clinical, electrophysiologic, or vascular improvements were observed in untreated legs.Ischemic neuropathy might be a reversible condition, and therapeutic angiogenesis might be an effective treatment. The presence of diabetes does not preclude a response to this therapy.

This paper provides an analysis of the port marketing strategies of the two major Polish ports of Gdynia and Gdansk in the context of transition to a new commercial environment. Taking the opinions of users of both ports, marketing strategies are assessed for their effectiveness and the results from this scaled survey are then input to a multivariate framework to derive the main, Consolidated policy priorities. These priorities emerge rather more clearly for the port of Gdynia than for the port of Gdansk, although in each case, the preferences of clients are clear.

Background —Preclinical studies have indicated that angiogenic growth factors can stimulate the development of collateral arteries, a concept called “therapeutic angiogenesis.” The objectives of this phase 1 clinical trial were (1) to document the safety and feasibility of intramuscular gene transfer by use of naked plasmid DNA encoding an endothelial cell mitogen and (2) to analyze potential therapeutic benefits in patients with critical limb ischemia. Methods and Results —Gene transfer was performed in 10 limbs of 9 patients with nonhealing ischemic ulcers (n=7/10) and/or rest pain (n=10/10) due to peripheral arterial disease. A total dose of 4000 μg of naked plasmid DNA encoding the 165-amino-acid isoform of human vascular endothelial growth factor (phVEGF 165 ) was injected directly into the muscles of the ischemic limb. Gene expression was documented by a transient increase in serum levels of VEGF monitored by ELISA. The ankle-brachial index improved significantly (0.33±0.05 to 0.48±0.03, P =.02); newly visible collateral blood vessels were directly documented by contrast angiography in 7 limbs; and magnetic resonance angiography showed qualitative evidence of improved distal flow in 8 limbs. Ischemic ulcers healed or markedly improved in 4 of 7 limbs, including successful limb salvage in 3 patients recommended for below-knee amputation. Tissue specimens obtained from an amputee 10 weeks after gene therapy showed foci of proliferating endothelial cells by immunohistochemistry. PCR and Southern blot analyses indicated persistence of small amounts of plasmid DNA. Complications were limited to transient lower-extremity edema in 6 patients, consistent with VEGF enhancement of vascular permeability. Conclusions —These findings may be cautiously interpreted to indicate that intramuscular injection of naked plasmid DNA achieves constitutive overexpression of VEGF sufficient to induce therapeutic angiogenesis in selected patients with critical limb ischemia.

Objectives. We sought to determine the basis for restenosis within superficial femoral arteries (SFAs) and hemodialysis conduits treated with balloon-expandable stents. Background. Use of stents within coronary and peripheral vessels continues to increase exponentially. The mechanism of restenosis within stents placed at various vascular sites is not well understood. In particular, the implications of deploying a balloon-expandable stent in a compressible site are not well understood. Methods. After the serendipitous detection of stent deformation during intravascular ultrasound (IVUS) examination of a restenosed dialysis fistula, we evaluated a consecutive series of patients with stents placed in compressible vascular sites, including the SFA (six patients) and hemodialysis fistulae (five patients). Clinical, angiographic and IVUS examinations were performed to evaluate mechanisms of restenosis. Results. Stent compression was identified as the principal cause of restenosis in all dialysis conduits and SFAs. Stent deformity was not reliably identified by angiography; however, IVUS identified compression of two forms: eccentric deformation, implicating two-point compressive force, and complete circumferential encroachment of stent struts around the catheter, suggesting multidirectional compressive force. Despite redilation, secondary restenosis resulting from recurrent compression recurred in most sites. Conclusions. Restenosis within balloon-expandable endovascular stents may occur as a result of stent compression, a phenomenon readily detected by IVUS, but often not by angiography. These findings have significant implications for the use of balloon-expandable stents within vascular sites subject to extrinsic compression, such as hemodialysis conduits, the adductor canal segment of the SFA and carotid arteries. (J Am Coll Cardiol 1997;29:328–38)

The age-adjusted prevalence of peripheral arterial disease (PAD) in the U.S. population has been estimated to approach 12%. The clinical consequences of occlusive peripheral arterial disease (PAD) include pain on walking (claudication), pain at rest, and loss of tissue integrity in the distal limbs; the latter may ultimately lead to amputation of a portion of the lower extremity. Surgical bypass techniques and percutaneous catheter-based interventions may be used to successfully revascularize the limbs of certain patients with PAD. In many patients, however, the anatomic extent and distribution of arterial occlusion is too severe to permit relief of pain and/or healing of ischemic ulcers. No effective medical therapy is available for the treatment of such patients. The purpose of this clinical protocol is to document the safety of therapeutic angiogenesis achieved in this case by percutaneous catheter-based delivery of the gene encoding vascular endothelial growth factor (VEGF) in patients with PAD; and, as secondary objectives, investigate the bioactivity of this strategy to relieve rest pain and heal ischemic ulcers of the lower extremities. The rationale for this human protocol is based upon preclinical studies performed in a rabbit model of hindlimb ischemia. These studies are described in detail below and in the manuscripts enclosed in the Appendix to this proposal. In brief, a single intra-arterial bolus of VEGF recombinant human protein, delivered percutaneously to the ischemic limb via an intravascular catheter, resulted in angiographic, hemodynamic, physiologic, and histologic evidence of augmented collateral artery development. Subsequently, similar results were achieved using an angioplasty catheter with a hydrogel-coated balloon to deliver 400 micrograms of a plasmid containing the cDNA for VEGF to the internal iliac artery in the same animal model. Accordingly, we propose to administer arterial gene (VEGF) therapy to patients with rest pain and/or ischemic leg ulcers considered not to be candidates for conventional revascularization techniques. The dose of plasmid to be administered will be progressively escalated beginning with 500 micrograms for the first four patients, 1000 micrograms for the following six patients, 2000 micrograms for the third group of six patients, and 400 micrograms for the fourth group of six patients.

The acute and long-term results of percutaneous revascularization of the lower extremities are typically superior for inflow (iliac) than distal (superficial femoral artery SFA, popliteal, or infrapopliteal disease). Accordingly, we investigated the utility of performing percutaneous revascularization for only inflow (iliac) lesions in pts with both inflow as well as distal disease. We treated 43 limbs in 36 pts (28 M, 8 F, age mean ± SD = 69 ± 8 yrs) with the combination of SFA occlusion and ipsilateral iliac artery lesions by percutaneous revascularization of the iliac artery lesion only. Ten lesions involved the common iliac artery, 18 involved both the common and the external iliac arteries, and 15 consisted of external iliac artery stenosis. All pts were symptomatically Rutherford class 3 and/or above. Mean ankle-brachial index (ABI) pre-procedure was 0.55 ± 0.19. Ipsilateral iliac artery stenosis, determined by quantitative angiography, was 80 ± 12%. All iliac lesions were treated with percutaneous transluminal angioplasty (PTA) ± stent placement. PostPTA, iliac artery stenosis decreased to 8 ± 8%. Of the 43 treated limbs, 40 (93%) were associated with improvement by at least one Rutherford class. One month post-procedure, mean ABI improved to 0.63 ± 0.19(p l 0.009). Complications were limited to 1 instance of arterial dissection which was successfully treated with a stent. Six-month follow-up was available on 24/43 limbs; 19/24 (79%) continued to show improved symptoms measured by Rutherford class. ABI's were remeasured at six months in 22 pts, and 18/22 (82%) showed improved ABI compared to baseline. Conclusion Percutaneous revascularization limited to iliac artery stenosis in patients with ipsilateral superficial femoral artery occlusion, by augmenting arterial inflow via a patent profunda, is frequently sufficient to produce clinical improvement of disabling symptoms.

Restenosis at stented sites has been attributed to neointimal proliferation. Stent collapse from external compression may also contribute to restenosis (Resten). We performed PTA and stenting in 6 hemodialysis conduits in five patients. Four subclavian and two brachiocephalic vein stenoses were initially treated with PTA and Palmaz stents, All sites developed early restenosis (mean time = 3.3 ± 2 months). Whereas angiography suggested a classic proliferative mechanism of restenosis, intravascular ultrasound (IVUS) demonstrated eccentric stent collapse: stent configuration was ovoid or slitlike, rather than circular, and struts were not apposed to the vessel wall, but instead were protruding into the lumen directly abutting the IVUS probe. Neointimal proliferation was absent in all cases, Redilation was performed in all cases, with additional stents placed in the 4 subclavian veins. All 6 vessels subsequently restenosed a second time by stent collapse (mean time = 4.7 ± 2 months). Download : Download high-res image (92KB) Download : Download full-size image Pre-PTA Post-Stent Resten Redilate Resten #2 Redilate #2 %Stenosis 73(±21) -21(±23) 58(±11) -211±21) 83(+27) -5(±18) Conclusions 1. Restenosis at stent sites may be caused by stent collapse due to external compression. 2. Stent collapse is poorly visualized byangiography, but readily identified by IVUS