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M L Marin

Publications and source records attributed to M L Marin.

At least 73 records · Page 4Linked to original sources

Increased IL-1, IL-6 and TNF alpha secretion and mRNA levels in WEHI-3 cells exposed to cyclopiazonic acid.

The effects of the mycotoxin cyclopiazonic acid (CPA) on cytokine secretion and gene expression were evaluated in the WEHI-3 murine macrophage cell line. Lipopolysaccharide (LPS)-stimulated and non-stimulated cells were exposed to various concentrations of CPA and culture supernatants were assessed for interleukin (IL)-1 beta, IL-6 and TNFalpha by ELISA. Without LPS stimulation, only IL-6 was increased by CPA at 5000 ng/ml after 1, 2 and 3 days. With LPS stimulation, IL-1 beta was elevated in the presence of 500 and 1000 ng/ml of CPA at 1 day and 500, 1000 and 5000 ng/ml at 2 days and 3 days. TNF alpha was increased by 1000 ng/ml CPA at 12 h and by 500, 1000 and 5000 ng/ml CPA at 1-3 days. IL-6 levels were increased in the presence of 100, 500 and 1000 CPA ng/ml at both 12 h and 3 days and in the presence of 100, 500, 1000 and 5000 ng/ml CPA at both 1 day and 2 days. The cytokine effects were further related to proliferation and cell viability using the MTT [3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide] assay. Proliferation was increased relative to controls in the presence of 50-1000 ng/ml of CPA in LPS-stimulated cells and in the presence of 500-1000 ng/ml CPA in unstimulated cells. In contrast, proliferation was markedly inhibited by 5000 ng/ml CPA in both stimulated and unstimulated cells. To relate the effect of CPA on IL secretion to mRNA transcript levels, LPS-stimulated cells were incubated with 1000 ng/ml of CPA for 2, 4, 8, 12 and 24 h and cytokine mRNA levels were evaluated using RT-PCR in combination with Southern hybridization analysis. In the presence of LPS only, IL-1 beta and IL-6 mRNA peaked at 8 h and 4 h, respectively, and then decreased whereas TNF alpha mRNA was strongly expressed from 2-8 h and markedly decreased at 12 h. In the presence of LPS and CPA, however, IL-1 beta and IL-6 mRNA levels gradually increased up to 24 h reaching 2.5 and 29-fold higher than controls, respectively. In contrast, TNF alpha mRNA levels slowly decreased after 8 h but remained markedly elevated relative to controls. Taken together, these results suggest that CPA can superinduce both secretion and mRNA levels of proinflammatory cytokines associated with macrophage activation. Cytokine upregulation was not always consistent with proliferative effects.

Analysis of Variance↗

Endoluminal therapy with endovascular grafts.

The addition of balloon-expandable stents to conventional graft material allows minimally invasive repair of aortic and other aneurysms, arterial occlusions, and arterial trauma. Vascular access can be made at a site far from the pathology.

Aneurysm↗

c-MYC oncoprotein production in experimental vein graft intimal hyperplasia.

PURPOSE: The expression of c-MYC oncoprotein in proliferating smooth muscle cells (SMCs) was analyzed in an experimental model of vein graft intimal thickening. METHODS: Superficial epigastric vein grafts were inserted into the femoral arteries of male Sprague-Dawley rats. The vein grafts were harvested at 6 hr, 2 days, 1 week, 2 weeks, and 4 weeks after grafting and were rapidly frozen in liquid nitrogen. Immunohistochemical labeling and morphologic analysis of vein graft sections with a double staining technique were used to identify c-MYC/alpha SMC actin and proliferating cell nuclear antigen (PC10)/alpha SMC actin within intimal cells. c-MYC/alpha SMC actin and PC10/alpha SMC actin positive cells were quantitated in the perianastomotic area (R-1) and the body of the graft (R-2) for each time period. Total wall and intimal thickness of perfusion fixed vein grafts were measured with a computer digitized system. RESULTS: Intimal and total wall thickening in the R-1 region peaked at 1 week (27.4 and 579.4 microns respectively) and were significantly thicker (P < 0.01) than the same region at 6 hr after graft implantation (6.0 and 113.5 microns respectively). Staining for c-MYC and PC10 in R-1 was also significantly higher (P < 0.05) at 1 week (5.75 and 7.00 positive cells/10 cells, respectively) compared with that at 6 hr (1.5 and 1.33, respectively). The R-1 region stabilized and remodeled over the following 3 weeks, while c-MYC and PC10 staining progressively decreased. In the R-2 region, intimal thickness significantly increased (P < 0.05) from 6 hr (4.0 micrometers) to 1 week (12.0 micrometers) and stabilized, while total wall thickness increased throughout the first week and the difference became significant at 2 weeks (P < 0.05). Staining for c-MYC and PC10 paralleled the staining in R-1 with a significant peak at 1 week (P < 0.05). CONCLUSIONS: c-MYC oncoprotein is expressed early after experimental vein grafting, with peak expression at 1 week. This occurs during a period of maximal intimal thickening, SMC proliferation, and increased expression of PC10. Expression of c-myc protooncogene may contribute to the induction and regulation of SMC proliferation, producing intimal hyperplasia.

Actins↗

Fluoroscopically assisted thromboembolectomy: an improved method for treating acute arterial occlusions.

We performed bilateral femoral artery dissections in a single 50 kg mongrel dog. Digital fluoroscopic arteriograms documented the luminal diameter of the left iliac and right superficial femoral arteries. Balloon thrombectomy catheter passage was performed through hemostatic sheaths by 12 surgeons. Embolectomy balloons were filled with radiographic contrast material and the balloon catheter diameter was compared with the underlying vessel diameter. The percentage of overdistention of the embolectomy balloon relative to the arterial wall was 23% +/- 5% in the iliac artery and 40% +/- 13% in the femoral artery. Over a 25-month period, we used fluoroscopically assisted thromboembolectomy to treat 21 patients with acute arterial or graft occlusions. As the balloon was gently withdrawn to extract intravascular thrombus, deformities of the compliant balloon profile caused by underlying arterial lesions were identified fluoroscopically and their locations recorded to facilitate further treatment. After initial clot removal in these 21 patients, 15 residual lesions were documented. Repeat thrombectomy (n = 8), balloon angioplasty (n = 3), and placement of intravascular stents (n = 4) eliminated all 15 lesions. Luminal continuity was successfully restored in all 21 of these patients, 10 of whom required distal open vascular reconstruction to correct existing outflow artery disease. Fluoroscopically assisted thromboembolectomy is a simple and safe method for treating acute arterial or graft occlusions in patients with diffuse arteriosclerosis. It minimizes arterial damage and blood loss during balloon thrombectomy and reduces the need for intravascular contrast agents. It also has the potential to facilitate accurate identification, localization, and treatment of significant underlying arterial lesions.

Adult↗

Somatosensory evoked potential monitoring during carotid surgery.

Controversy exists over the value of intraoperative monitoring and shunting in patients undergoing carotid endarterectomy. Although it is widely believed that contralateral carotid occlusion and previous stroke mandate intraoperative shunting, the susceptibility of these two groups of patients to cerebral ischemia during carotid artery endarterectomy is not well defined. Somatosensory evoked potentials (SSEPs) were monitored in 113 carotid artery endarterectomy patients. Of these, 32 (28.3%) had a previous stroke, 24 (21.2%) had a contralateral carotid occlusion and 33 (29.2%) were diabetic. There were no deaths and only one perioperative stroke (0.9%). Cerebral ischemia occurred in 14 patients (12.4%). Six of these patients had a contralateral carotid occlusion. Some 29 patients (25.7%) were shunted, including 10 with contralateral carotid occlusions that did not have major SSEP changes. In the latter half of the study, 14 patients with contralateral carotid occlusions were selectively shunted (six shunted, eight not shunted) with no neurological complications. Thirty-two patients with prior strokes were selectively shunted (nine shunted, 23 not shunted); of these, one shunted patient undergoing combined carotid artery endarterectomy and coronary artery bypass grafting had a perioperative stroke. Intraoperative monitoring with SSEPs accurately identifies cerebral ischemia secondary to carotid clamping as well as patients requiring shunts. With use of intraoperative SSEP monitoring, selective shunting may be safely performed in patients with a contralateral carotid occlusion or a previous stroke.

Adult↗

David M. Hume Memorial Lecture. Impact of endovascular technology on the practice of vascular surgery.

Endovascular treatment techniques have already replaced some vascular operations. The likelihood is that new endovascular techniques involving stents and stented grafts will replace additional vascular operations. All these treatments involve the use of catheter-guidewire, balloon, and imaging modalities, particularly digital fluoroscopy. These modalities have already and will increasingly help to improve and simplify standard vascular operations such as thromboembolectomy, infrainguinal bypasses, and management of aneurysms and arteriovenous fistulas. Accordingly, vascular surgeons must become familiar with and use these endovascular methods and techniques. This can be accomplished in a variety of ways which includes working as part of a multidisciplinary vascular treatment group in which various specialists collaborate to provide the best, most cost-effective care to vascular disease patients.

Forecasting↗

Comparison of endovascular and conventional vascular prostheses in an experimental infection model.

INTRODUCTION: The causes and management of prosthetic graft infections have been extensively studied for conventional bypass grafts; however, the infectivity and therapy for endovascular graft infections are completely unknown. The aim of this study was to compare the biologic properties of infected aortic grafts when inserted by endoluminal or standard transabdominal techniques. METHODS: Eighteen dogs underwent placement of polytetrafluoroethylene grafts in their infrarenal aortas either by an endovascular technique (8) or a standard interposition technique (10). Endovascular grafts were constructed from polytetrafluoroethylene (3 cm) and two balloon-expandable stents coaxially mounted onto a balloon catheter delivery system. The grafts were inserted through a left carotid arteriotomy under fluoroscopic control. Initially, seven grafts were infected with decreasing inocula of Staphylococcus aureus, starting at 10(7) organisms per ml for 30 minutes and then rinsed briefly (10 seconds) in normal saline solution, until a 50% infective dose for the standard grafts was determined to be 10(2) organisms per ml. After this initial experiment, a second group of 11 dogs were compared at a concentration of 10(2) S. aureus per ml. Five dogs underwent endovascular repair, and six dogs had standard graft interpositions after an identical period of bacterial exposure. All grafts were removed at 2 weeks under sterile conditions and were submitted for quantitative culture analysis. RESULTS: Three of the six dogs (50%) with standard grafts appeared to clear their infections, whereas only one of the five dogs (20%) with an endovascular graft was free of organisms at 14 days. This results was further manifested by statistically significant lower postmortem colony counts in the standard grafts (p < 0.01). CONCLUSIONS: The endoluminal position of the graft and its proximity to the arterial wall do not appear to provide protection against infection. These data suggest that if endovascular grafts become infected, they may be in a disadvantaged position for host defense mechanisms to be effective.

Animals↗

Endovascular aortounifemoral grafts and femorofemoral bypass for bilateral limb-threatening ischemia.

PURPOSE: Although axillobifemoral bypass procedures have a lower mortality rate than aortobifemoral bypass procedures, they are limited by decreased patency, moderate hemodynamic improvement, and the need for general anesthesia. This report describes an alternative approach to bilateral aortoiliac occlusive disease using unilateral endovascular aortofemoral bypass procedures in combination with standard femorofemoral reconstructions. METHODS: Seven patients who had bilateral critical ischemia and tissue necrosis in association with severe comorbid medical illnesses underwent implantation of unilateral aortofemoral endovascular grafts, which were inserted into predilated, recanalized iliac arteries. The proximal end of the endovascular graft was fixed to the distal aorta or common iliac artery with a Palmaz stent. The distal end of the graft was suture-anastomosed to the ipsilateral patent outflow vessel, and a femorofemoral bypass procedure was then performed. RESULTS: All endovascular grafts were successfully inserted through five occluded and two diffusely stenotic iliac arteries under either local (1), epidural (5), or general anesthesia (1). The mean thigh pulse volume recording amplitudes increased from 9 +/- 3 mm to 30 +/- 7 mm and from 6 +/- 2 mm to 26 +/- 4 mm ipsilateral and contralateral to the aortofemoral graft insertion, respectively. In all cases the symptoms completely resolved. Procedural complications were limited to one local wound hematoma. No graft thromboses occurred during follow-up to 28 months (mean, 17 months). CONCLUSIONS: Endovascular iliac grafts in combination with standard femorofemoral bypass grafts may be an effective alternative to axillobifemoral bypass in high-risk patients who have diffuse aortoiliac occlusive disease, particularly when bilateral axillary-subclavian disease is present.

Aged↗

Immunolocalization and temporal distribution of cytokine expression during the development of vein graft intimal hyperplasia in an experimental model.

PURPOSE: Vein graft stenosis caused by intimal hyperplasia (IH) accounts for 30% to 50% of late bypass graft failures; however, the biochemical mediators of vein graft IH have been poorly defined. We attempted to evaluate the spatial and temporal distribution of five principal cytokines (interleukin-1 beta [IL-1 beta], platelet-derived growth factor-AA [PDGF-AA], basic fibroblast growth factor [bFGF], interferon gamma [INF gamma], and tumor necrosis factor alpha [TNF-alpha]) during the development of IH in a rat vein graft model. METHODS: Rat epigastric vein interposition grafts in the femoral artery were harvested at 6 hours, 2 days, 1 week, 2 weeks, and 4 weeks after the grafting procedure and studied with immunohistochemical and standard histologic techniques. The cytokine expression in the endothelium and media/neointima was quantified as the percentage of immunopositive cells per high-power field. RESULTS: Maximal hyperplasia occurred 2 weeks after the grafting procedure. Peak expression of IL-1 beta and bFGF occurred by 2 days. PDGF-AA expression paralleled the development of IH, peaking at 2 weeks and then declining. TNF-alpha expression increased at 1 week and remained elevated. INF gamma was seen only in control grafts. CONCLUSIONS: The coordinated early release of IL-1 beta and bFGF and the down-regulation of INF gamma seem to trigger an inflammatory response, thereby initiating IH. The process then is propagated by the release of PDGF-AA and TNF-alpha, with concomitant smooth muscle cell proliferation and production of extracellular matrix. It is likely that this complex milieu of local paracrine signaling is required to generate the hyperplastic response seen in failing vein grafts.

Actins↗

The merit of polytetrafluoroethylene extensions and interposition grafts to salvage failing infrainguinal vein bypasses.

PURPOSE: The purpose of this study was to evaluate the merit of polytetrafluoroethylene (PTFE) extensions and interpositions for the management of failing infrainguinal vein bypass grafts. METHODS: The treatment of 133 failing vein grafts in 125 patients over a 10-year period was retrospectively reviewed. Twenty-two graft-threatening lesions were detected in patients who did not have a usable autogenous vein conduit as determined by preoperative and intraoperative evaluations. A PTFE extension or interposition graft was used for the necessary reconstruction in all cases. RESULTS: Ten lesions were within the vein graft, 11 were proximal to the graft in the femoral or popliteal artery segments, and one was distal to the graft in the popliteal artery. The treatment of these lesions included 19 extensions and three mid graft interpositions. The vein graft lesions developed significantly sooner (mean 10.6+/-2.5 months) after the bypass (p<0.05) than the arterial lesions (mean 28.0+/-6.1 months). The 3-year cumulative secondary patency rate for these vein grafts treated with PTFE extensions or interpositions was 84%+/-8%. This was not significantly different from the 3-year cumulative secondary patency rate for vein grafts treated with vein extensions or interpositions at our institution over the same time period (82%+/-10%). The 3-year limb salvage rates were 95% and 89%, respectively. CONCLUSIONS: These results indicate that PTFE extensions and interpositions can be used successfully to maintain the patency of failing vein grafts and may serve to prolong limb salvage in patients without any usable autogenous vein. Early reintervention with a PTFE conduit in this difficult group of patients is appropriate to salvage a failing vein graft.

Aged↗

Polytetrafluoroethylene bypasses to infrapopliteal arteries without cuffs or patches: a better option than amputation in patients without autologous vein.

PURPOSE: This study was undertaken to evaluate our results of polytetrafluoroethylene (PTFE) tibial and peroneal artery bypasses done for limb salvage. METHODS: Within a group of patients undergoing infrainguinal limb salvage bypasses at our institution between January 1986 and May 1995, 63 patients faced an immediate amputation, had no autologous vein on duplex examination and operative exploration, and had only a tibial or peroneal artery as an outflow vessel for bypass. Most of these patients (82%) had two or more prior ipsilateral infrainguinal bypasses. These 63 patients underwent 66 PTFE bypasses to a tibial or peroneal artery without a distal anastomotic vein cuff or an adjunctive arteriovenous fistula. Our results were then compared with those reported from infrapopliteal (crural) bypasses performed with alternate autologous vein sources or PTFE in conjunction with various recommended adjuncts. RESULTS: The 3- and 5-year cumulative primary graft patency rates for our PTFE infrapopliteal bypasses were 39%+/-7% and 28%+/-9%, respectively. Secondary graft patency rates were 55%+/-8% and 43%+/-10% at 3 and 5 years, respectively. Limb salvage rates were 71%+/-7% at 3 years and 66%+/-8% at 5 years. Two-year actuarial patient survival rate was only 67%+/-7%. CONCLUSIONS: These results indicate that a PTFE bypass to an infrapopliteal artery remains a worthwhile option in patients without usable autologous vein. The secondary patency and limb salvage rates were acceptable in this setting and were not significantly different from the best results reported with prosthetic tibial/peroneal bypasses with distal vein cuffs or patches (74% at 1 year; 58% at 3 years), arteriovenous fistulas (71% at 1 year) or composite arm vein grafts (39% and 29% at 3 and 5 years, respectively).

Actuarial Analysis↗

Effects of mycotoxins on cytokine production and proliferation in EL-4 thymoma cells.

The thymoma cell line EL4.IL-2 (EL-4) was used as a T-cell model to assess the immunotoxic effects of several mycotoxins produced by the Aspergillus-Penicillium and the Fusarium groups. EL-4 cells were stimulated with phorbol 12-myristate 12-acetate (PMA) in the presence of mycotoxins at various concentrations for 5 d and culture supernatants were analyzed for interleukins (IL) IL-2 and IL-5 by enzyme-linked immunosorbent assay (ELISA). The cytokine effects were further related to proliferation and cell viability using the MTT [3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide] assay with absorbance at 570 nm (A570) as the endpoint indicator. IL-2 and IL-5 levels were dramatically increased by cyclopiazonic acid at 50-1000 ng/ml, whereas IL-2 was significantly decreased at 10 microgram/ml. Proliferation was slightly increased at 100-1000 ng/ml cyclopiazonic acid but markedly depressed at 5 and 10 microgram/ml. When EL-4 cells were exposed to 5 and 10 microgram/ml of ochratoxin A, IL-2 production was markedly increased while IL-5 production was significantly decreased. The A570 was significantly decreased by ochratoxin A at 10 microgram/ml. IL-2 and Il-5 production was almost totally suppressed by patulin at concentrations > or = 500 ng/ml and by T-2 toxin at > or = 5 ng/ml. These effects occurred concurrently with marked depression of A570 in the MTT assay. Although A570 was unaffected by either zearalenone or alpha-zearalenol exposure, both IL-2 and IL-5 levels were significantly elevated by these toxins at 5 or 10 microgram/ml. IL-2 and IL-5 production were not affected in EL-4 cells cultured with either the Aspergillus-Penicillium toxins aflatoxin B1 and secalonic acid or the Fusarium toxins wortmannin, fumonisin B1, or fusaric acid at concentrations up to 10 microgram/ml. In total, the EL-4 culture studies indicated that cyclopiazonic acid, ochratoxin A, zearalenone, and alpha-zearalenol could stimulate cytokine production whereas patulin and T-2 toxin were inhibitory. Cytokine dysregulation was not always related directly to perturbations in proliferation. The results suggest that the EL-4 thymoma cell line could be a simple and effective in vitro model for evaluating immunotoxicity of various classes of environmental chemicals.

Androstadienes↗

Endovascular graft repair of penetrating subclavian artery injuries.

PURPOSE: Penetrating subclavian arterial injuries are often difficult to treat. Standard surgical techniques require wide exposure and dissection in traumatized areas, which is often challenging. This report summarizes the early results of endovascularly placed stented grafts for the treatment of penetrating subclavian arterial trauma. METHODS: Six patients with penetrating injuries of the subclavian artery had stented grafts inserted to repair five pseudoaneurysms and one arteriovenous fistula. The stented grafts consisted of a polytetrafluoroethylene graft sutured over a balloon-expandable Palmaz stent. The devices were inserted from an ipsilateral brachial arteriotomy and deployed using fluoroscopic guidance in the operating room. RESULTS: Immediate success was obtained in all procedures (100%). All patients continue to have patent grafts with a follow-up ranging from 7 to 30 months (mean 19 months). The only procedure-related complication was the need for a brachial artery patch angioplasty at the site of device insertion in the first patient. There was one other patient who developed a stent fracture at 8 months; a second stent was inserted. Duplex studies up to 24 months later show no recurrence in this patient. CONCLUSIONS: Endovascular stented grafts offer an effective, less invasive alternative to standard techniques in treating traumatic arterial lesions. Early results are encouraging, but long-term follow-up will be necessary to fully delineate the effectiveness of this technique.

Adult↗

Endovascular stents and stented grafts for the treatment of aneurysms and other arterial lesions.

The combination of prosthetic graft and intravascular stent technologies will probably become an important part of the treatment for aneurysmal and occlusive disease as well as for traumatic vascular injuries. This technology potentially permits reduced operative morbidity and mortality rates as well as decreased intraoperative blood loss, cost, and hospital stay, with ultimately improved patient care. Once additional experience with this important new technique has been obtained, randomized, prospective trials comparing standard therapy to endovascular grafting procedures will be needed to substantiate this form of therapy for the treatment of various arterial lesions.

Aneurysm↗

Transfemoral, endovascular stented graft repair of an abdominal aortic aneurysm.

Endovascular aortic graft implantation is a new procedure for the repair of arterial aneurysms. We report on the first such case successfully performed in the United States. A 76-year-old man with severe oxygen-dependent pulmonary insufficiency, coronary artery disease, and recurrent ventricular tachyrhythmia was also diagnosed as having a 7.5-cm infrarenal abdominal aortic aneurysm. Because of the high risks associated with conventional surgical repair, consent was obtained for compassionate use of an experimental device. Using local anesthesia, a 22-mm Dacron prosthesis was inserted under fluoroscopic guidance through an open, left transfemoral route. Completion arteriography demonstrated aneurysm exclusion. No blood transfusion was required and there were no perioperative complications. Further technical refinements and clinical trials will be required prior to the broad implementation of this technique.

Aged↗

Placement of endovascular stented grafts via remote access sites: a new approach to the treatment of failed aortoiliofemoral reconstructions.

Endovascular grafting is a technique that combines the use of intravascular stents and prosthetic grafts to fabricate devices with unique properties. The purpose of this study is to describe the use of endovascular graft technology in the treatment of failed or failing standard aortoiliofemoral reconstructions. Over a 15-month period five patients with limb-threatening ischemia and failed aortofemoral or iliofemoral reconstructions underwent successful placement of six endovascular grafts to revascularize seven severely ischemic lower extremities. Standard thin-walled 6 mm polytetrafluoroethylene grafts and Palmaz balloon-expandable stents were used to fashion each reconstruction. In addition to the primary endovascular grafts, three patients underwent immediate femoropopliteal bypasses to improve distal outflow and one patient had a femorofemoral bypass graft to restore circulation to the contralateral ischemic extremity. The ankle/brachial indices of all patients significantly improved after the procedure (from a mean of 0.32 to a mean of 0.75) and all grafts are patent to date (mean follow-up 10 months). There were no deaths or limb loss in this group of patients. These favorable results indicate that this minimally invasive approach, which permits a new arterial graft to be inserted through a remote access site, is a valuable method for providing unobstructed arterial inflow after aortoiliofemoral graft failure. This procedure may be particularly valuable when there are contraindications to the use of axillary arteries or the thoracic aorta as alternatives to complex reoperative abdominal aortic surgery.

Aged↗