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Biomedical subjects

L M Messina

Publications and source records attributed to L M Messina.

At least 37 records · Page 2Linked to original sources

Endovascular repair of abdominal aortic aneurysm using a pararenal fenestrated stent-graft.

PURPOSE: To report an unusual case of endovascular abdominal aortic aneurysm (AAA) exclusion in which a fenestrated stent-graft was used to seal a proximal Type I endoleak. METHODS AND RESULTS: An 84-year-old man with a 6.0-cm AAA underwent an aortomonoiliac aneurysm exclusion procedure that was complicated by a proximal endoleak. Because the patient had no right kidney, an additional stent-graft was designed to cover the right renal artery stump while preserving left renal perfusion through a fenestration in the graft material. This approach was successful in obliterating the endoleak around the proximal attachment site, but flow through the lumbar arteries remained. CONCLUSIONS: The use of a fenestrated stent-graft is feasible, but the type of fenestration in this case has limited applicability owing to the rarity of patients with suitable anatomy.

Aged↗

Aortomonoiliac endovascular grafting combined with femorofemoral bypass: an acceptable compromise or a preferred solution?

The relative merits of aortomonoiliac and bifurcated stent-graft configurations depend on the patient's arterial anatomy and clinical status. Aortomonoiliac stent-grafts are simple to make, simple to insert, and versatile. They are most useful when the iliac artery anatomy is severely distorted and the patient is old, sick, and inactive. The main problems with this approach are all consequences of femorofemoral bypass. The bifurcated stent-graft is the preferred alternative in healthy patients, because it ensures flow to both common iliac arteries, thereby eliminating the need for femorofemoral bypass. However, bifurcated stent-grafts and their delivery systems are difficult to make and difficult to deploy, especially when the iliac anatomy is distorted or emergency circumstances preclude preoperative sizing. This article addresses the advantages and disadvantages of the aortomonoiliac graft.

Aortic Aneurysm, Abdominal↗

Surgical management of subclavian-vein effort thrombosis as a result of thoracic outlet compression.

BACKGROUND: There is considerable variability and controversy in the current management of subclavian-vein effort thrombosis. The purpose of this study was to determine the long-term effectiveness and the functional outcome of our preferred treatment strategy of early thrombolysis/recanalization and prompt extensive supraclavicular decompression. PATIENTS AND METHODS: Thirty-three patients who ranged in age from 15 to 60 years underwent operative decompression of 34 primary subclavian-vein thromboses, one of which was bilateral. There were 21 patients with acute thrombosis 7 of whom had had prior unsuccessful balloon venoplasty, 1 with stent placement and 8 patients with chronic/recurrent thrombosis 5 of whom had had 9 unsuccessful prior operations for attempted decompression. Four patients had high-grade symptomatic stenosis and positional occlusion. A supraclavicular approach was used in 32 cases and, in 23 cases, was complemented by an infraclavicular (n = 21) or transaxillary (n = 2) incision. Complete subclavian-vein decompression was achieved by first-rib resection (n = 31), scalenectomy (n = 33), and circumferential venolysis (n = 34). RESULTS: Follow-up was obtained in 30 patients at a mean of 31 months. Twenty of the 21 patients with acute thrombosis had a complete resolution of symptoms with a return to full activity; the other patient was lost to follow-up. Four of the 8 patients with chronic thrombosis reported a mild relief of symptoms but still had limitations of activities of daily living. All of the patients with high-grade symptomatic stenosis with positional occlusion had a complete relief of symptoms and a return to full activity. CONCLUSION: The optimal management of acute effort thrombosis of the subclavian vein includes anticoagulation therapy, thrombolysis/recanalization, confirmatory positional venography, and early supraclavicular decompression of the subclavian vein. In the patients with chronic subclavian-vein thrombosis and positional venographic evidence of compression of first-rib bypass graft collaterals, the initial anticoagulation therapy should be followed by the surgical decompression of the collaterals. The supraclavicular approach alone or with an infraclavicular incision provides optimal exposure for scalenectomy, total first-rib resection, and circumferential venolysis.

Adolescent↗

In situ autogenous reconstruction of the thoracoabdominal aorta and branches for treatment of an infected thoracoabdominal aortobifemoral bypass graft.

Graft infection is an uncommon but potentially lethal complication of prosthetic aortic repair. We describe a novel technique for upper abdominal aortic and visceral revascularization after percutaneous drainage and antibiotics failed to cure a thoracofemoral prosthetic graft infection. One week after axillofemoral and femorofemoral bypass grafting, the infected thoracoabdominal graft was removed and a bifurcated iliac artery autograft was used to replace the upper abdominal aorta and revascularize the abdominal viscera. The infected graft was removed from the thorax and retroperitoneum, the infection resolved, and the patient remained well until his death of lung cancer 9 years later.

Abdominal Abscess↗

Reoperation for recurrent chronic visceral ischemia.

PURPOSE: Recurrent visceral ischemia after a failed visceral revascularization occurs in up to one third of patients, yet no comprehensive report has described the management of this problem. The purpose of this study was to examine the presentation, surgical management, and outcome of patients with recurrent visceral ischemia. METHODS: Between 1959 and 1997, 109 patients underwent primary visceral revascularization at the University of California, San Francisco. Nineteen patients (17.4%) had recurrent visceral ischemia (12 chronic visceral ischemia, seven acute visceral ischemia). Fourteen additional patients with recurrent chronic visceral ischemia were referred after failed primary revascularization (two patients underwent multiple operations before referral). Thirty visceral reoperations were performed for recurrent visceral ischemia in 24 patients (10 patients with recurrence at University of California, San Francisco, 14 referred patients). Symptom-free and overall survival rates were determined by life table analysis. RESULTS: Of seven patients (6.4%) who had recurrent acute visceral ischemia, six (85.7%) died of bowel infarction. Twelve patients (11%) had recurrent chronic visceral ischemia. Patients with recurrent chronic visceral ischemia received their diagnoses earlier and lost less weight than at their initial presentation (p = 0.004 and 0.001, respectively). Recurrent ischemia was associated with younger age, greater weight loss, and modification of surgical technique at the time of initial operation (p = 0.5, 0.009, and 0.02, respectively). For 20 (90.9%) of the 22 first reoperations, antegrade aortovisceral bypass (n = 10) or transaortic visceral endarterectomy (n = 10) was used. Multiple techniques (four antegrade bypass, two retrograde bypass, one endarterectomy, one anastomotic revision) were used in the eight second or third reoperations. Postoperative mortality and complication rates were 6.7% and 33.3%, respectively. Symptoms recurred in six of 22 patients (27.3%) after the first reoperation, three of whom were cured or improved after additional reoperations. The life table symptom-free survival rate after reoperation was 77.3% and 62.8% at 1 and 5 years, respectively. The life table overall survival rate after reoperation was 74.6% at 5 years. CONCLUSIONS: Recurrent visceral ischemia is not uncommon after primary visceral revascularization. These results show that reoperation for recurrent chronic visceral ischemia can be accomplished safely and effectively with established revascularization techniques. Furthermore, after repeat visceral revascularization patients achieve durable relief of symptoms and have life expectancy rates comparable with those of patients who undergo primary visceral revascularization.

Chronic Disease↗

Endovascular repair of abdominal aortic aneurysm: getting out of trouble.

The standard techniques of endovascular aneurysm repair sometimes fail to produce atraumatic stent-graft delivery of hemostatic implantation, and additional maneuvers are required to avoid conversion to open repair. Between June 1996 and May 1997 elective endovascular aneurysm repair was performed in 33 high risk patients, using a Z-stent-based prosthesis. Challenging anatomic features included: short neck (< 15 mm) in four cases, angulated neck (> 60 degrees) in seven, iliac aneurysm in six, and iliac tortuosity (> 80 degrees) in 24. There were no deaths, no renal failure, no pulmonary failure, no graft thrombosis, no migration, and no conversions to open surgery. Deviations from standard technique were required to treat iliac artery dissection, iliac artery stenosis, and leaks resulting from proximal stent malalignment, proximal stent malposition, and distal stent malposition. The necessary adjunctive maneuvers included: additional stent placement, additional stent-graft placement, and balloon dilatation. Mean operating time was 191 +/- 72 min, mean contrast volume was 148 +/- 76 ml, and mean blood loss was 314 +/- 427 ml. Mean time from operation to discharge from the hospital was 3.5 +/- 1.67 days. These short-term results demonstrate that endovascular aneurysm repair is safe and effective in high risk patients, only if adjunctive maneuvers are available to supplement standard technique.

Aged↗

Innominate artery reconstruction: over 3 decades of experience.

SUMMARY BACKGROUND DATA: Symptomatic atherosclerotic occlusive disease of the innominate artery is a threatening disease pattern that offers a major challenge in achieving definitive surgical repair. To assess the evolution of treatment strategies and their outcomes for this disease, the authors undertook a review of the cumulative experience for more than 3 decades at one institution. METHODS: Between 1960 and 1997, 94 patients (mean age, 62 years) underwent direct innominate artery revascularization for occlusive atherosclerotic disease to relieve neurologic (n = 85) and/or right upper extremity (n = 26) symptoms or asymptomatic critical stenosis (n = 3). The pattern of atherosclerotic involvement revealed by angiography included critical stenosis (n = 77), complete occlusion (n = 10), and moderate stenosis with plaque ulceration (n = 7). A common brachiocephalic trunk was present in five patients. Transsternal (n = 68) or transcervical (n = 4) innominate endarterectomy was performed in 72 patients and bypass grafting in 22. Forty-one patients underwent concomitant endarterectomy or bypass of innominate branches or adjacent arch vessels, and 3 had coronary bypass grafting. RESULTS: There were three perioperative deaths (3%), all due to cardiac causes. Postoperative morbidity included four strokes (three resolved), two myocardial infarctions, two transient ischemic attacks, and one sternal dehiscence. Follow-up ranged from 8 months to 20 years. Postoperative actuarial survival rate was 96% at 1 year, 85% at 5 years, and 67% at 10 years. Freedom from recurrence requiring reoperation was 100% at 1 year, 99% at 5 years, and 97% at 10 years. CONCLUSIONS: Innominate artery reconstruction is safe and durable when either endarterectomy or prosthetic bypass is used. The anatomic variation and disease distribution permit endarterectomy for most patients. The technique of innominate endarterectomy can be extended safely to outflow and adjacent vessels.

Adult↗

Femoral artery exposure for endovascular aneurysm repair through oblique incisions.

PURPOSE: To offer an alternative technique for accessing the femoral artery prior to endovascular grafting. TECHNIQUE: An oblique incision is made over the medial half of the inguinal ligament and continues to the femoral sheath, which is opened longitudinally. The distal external iliac artery and proximal common femoral artery are isolated. A tiny stab wound is made distal to the primary wound for femoral artery puncture and catheter access. CONCLUSIONS: Using an oblique incision at the level of the inguinal ligament optimizes exposure for endograft insertion and may minimize the frequency of serious wound complications.

Aneurysm↗

Induction of angiogenesis by lidocaine and basic fibroblast growth factor: a model for in vivo retroviral-mediated gene therapy.

A strategy of direct, in vivo retroviral-mediated gene therapy targeting capillary endothelial cells must provide an environment of active angiogenesis. Both lidocaine and basic fibroblast growth factor (bFGF) promote angiogenesis, but the angiogenic response invoked by these substances in normal skeletal muscle has not been fully characterized. We sought to characterize these agents' angiogenic effects in anterior tibialis muscles of male Sprague-Dawley rats. An injection of either 1% lidocaine with 1:100,000 epinephrine or alternate-day injections of bFGF (0.025 or 0.25 microgram) with or without heparin were tested (n = 6 muscles/condition). Rats were sacrificed 4, 7, 10, or 12 days later and muscles were evaluated histologically to determine the number of proliferating cells using 5-bromo-2'-deoxycytidine (BrdC) and evaluated for capillary density using Griffonia simplicifolia I (GSI) lectin. At all time points, lidocaine produced at least 20-fold greater capillary density and cellular proliferation than PBS control (P < 0.0001). Injections of high-dosage bFGF produced more than fivefold greater capillary density than control injections at 7 and 10 days (P < 0.001), and more than twofold greater proliferation at 4, 7, and 12 days (P < 0.001). Capillary density returned to control levels 12 days following bFGF administration, whereas it remained well above control levels for 12 days after lidocaine administration. To confirm that lidocaine can be utilized in gene therapy strategies targeting vascular endothelium and skeletal muscle fibers, concentrated pLJ retrovirus containing cDNA for the heat-stable human placental alkaline phosphatase (hpAP) marker gene was infused into the rat hindlimb vasculature 4 days post-lidocaine administration. Rats receiving pLJhpAP retrovirus demonstrated significant hpAP transgene expression in endothelial cells and myocytes 21 days after the lidocaine injection (n = 6 muscles). In contrast, controls receiving pLJhpAP infusion without prior lidocaine administration failed to demonstrate any hpAP transgene expression. Lidocaine treatment evokes a substantially higher proliferative response than bFGF and, importantly, a durable angiogenic response in skeletal muscle. Thus, lidocaine is an ideal agent to induce angiogenesis in preparation for direct in vivo retroviral-mediated gene therapy targeting vascular endothelium.

Alkaline Phosphatase↗

Visceral artery aneurysms.

Visceral artery aneurysms are an uncommon form of vascular disease that have a significant potential for rupture or erosion into an adjacent viscera, resulting in life-threatening hemorrhage. During the last decade, hepatic artery aneurysms have become the most commonly reported visceral artery aneurysm. This change likely reflects the increased use of percutaneous diagnostic and therapeutic biliary procedures, as well as increased use of diagnostic computed tomography after blunt abdominal trauma. A second significant development is the increased use of percutaneous catheter-based therapy in the management of visceral artery aneurysms. Nonetheless, a continued aggressive approach to the diagnosis and management of these unusual aneurysms remains warranted.

Aneurysm↗

Improved retroviral transduction efficiency of vascular cells in vitro and in vivo during clinically relevant incubation periods using centrifugation to increase viral titers.

Vascular cells are an important target for gene transfer because of their potential to deliver gene products both locally and systemically. Direct retroviral gene transfer to vascular cells in vivo has been limited by inefficient rates of transduction. We hypothesized that vascular cell transduction efficiency (TE), during short retroviral incubation periods, is significantly improved in vitro and in vivo using centrifugation to increase viral titer. Furthermore, we hypothesized a linear relationship between concentration of viable viral particles (measured as colony-forming units (CFUs)/cell) and retroviral TE during short incubation periods. Cultured rat pulmonary artery endothelial cells (RPAECs), rat aortic smooth muscle cells (RSMCs), and human iliac artery endothelial cells (HIAECs) demonstrated a strong correlation between TE and high concentrations of virus (> 100 CFU/cell) during retroviral incubation periods of 10 to 60 minutes. High titers, and thereby high concentrations, were achieved by centrifugation and resuspension in a fraction of the original volume. Titers was consistently increased tenfold, for a twentyfold increase in concentration by volume. A 20-minute incubation with a Moloney murine leukemia-derived retroviral vector coding for human placental alkaline phosphatase, pLJhpAP, at a concentration of 1150 CFU/cell yielded TEs of 10.6% +/- 0.7%, 40.4% +/- 1.6%, and 15.1% +/- 2.0% for RPAECs, RSMCs, and HIAECs, respectively. A similar effect was shown using the Moloney murine leukemia-derived MFGlacZ retroviral vector, coding for Escherichia coli beta-galactosidase. Increased titer and concentration had no effect on target cell viability, as shown by trypan blue exclusion. Although RSMCs had the most cells transduced in a given incubation period (p < 0.05), RPAECs had the highest replication rate (p < 0.05), suggesting the importance of factors other than cell cycle on retroviral TEs during short, clinically relevant incubation periods. In subsequent in vivo experiments, gene transfer was achieved in the rat carotid artery during a 20-minute incubation period infusing the concentrated pLJhpAP retrovirus after carotid balloon injury. Rats infused with virus 2 days after balloon injury exhibited hpAP activity (0 to 10 cells/section/rat) in the neointima of five out of six rats. Rats infused 4 days after balloon injury exhibited hpAP activity (0 to 25 cells/section/rat) in the media and adventitia of five out of five rats. Control rats that received the balloon injury alone or the balloon injury and unconcentrated retrovirus exhibited zero hpAP activity. We conclude that the TE of retroviral-mediated gene transfer to vascular cells in vitro and in vivo can be improved during short, clinically relevant incubation periods using centrifugation to increase retroviral titer, and thereby concentration of viable viral particles.

Alkaline Phosphatase↗

Systemic delivery of the interleukin-1 receptor antagonist protein using a new strategy of direct adenoviral-mediated gene transfer to skeletal muscle capillary endothelium in the isolated rat hindlimb.

Current gene therapy strategies using adenoviral vectors to target the lung or liver have been complicated by an acute inflammatory response that can result in loss of transgene expression as well as tissue injury and necrosis. Skeletal muscle comprises 40% of total body weight; it possesses a high density, accessible capillary network that is resistant to injury and thus may be a logical target for adenoviral vectors. We hypothesized that adenoviral transduction of the rat skeletal muscle capillary bed during vascular isolation would achieve efficient gene transfer sufficient to achieve systemic serum levels of a recombinant protein without significant tissue injury. During vascular isolation of the hindleg, a replication-incompetent adenovirus (Ad) encoding for either the marker gene, human placental alkaline phosphatase (hpAP), or interleukin-1 receptor antagonist (IL-1ra) was infused and subsequently flushed from the circulation after a 30-min dwell period. Gene transfer over a 10(9)-10(12) particle/ml range to the gastrocnemius capillary endothelium and muscle fibers was highly efficient and titer-dependent, reaching maximum transduction rates of 71 +/- 7% and 25 +/- 5%, respectively, 5 days after gene transfer (n = 3-8 rats/group, p < 0.05). hpAP transgene expression was barely detectable at 14 days. No significant tissue injury or necrosis of the skeletal muscle was observed at 5 and 14 days, and distant organ gene transfer was minimal or absent. Gastrocnemius muscle from rats (n = 4) given Ad-IL-1ra had 241 +/- 66 pg IL-1ra/mg protein at 5 days, while those given Ad-hpAP, negative control (n = 3) had 35 +/- 14 pg IL-1ra/mg protein (p < 0.05). Ad-IL-1ra rats (n = 4) had serum levels of 185 +/- 20 pg/ml IL-1ra at 5 days whereas Ad-hpAP control rats (n = 5) had no IL-1ra detectable (p < 0.0001). Athymic rats given Ad-IL-1ra (n = 6) had serum levels of 493 +/- 62 pg/ml IL-1ra 14 days after transduction, and IL-1ra was detected for up to 98 days. Sera from Ad-IL-1ra athymic rats significantly inhibited IL-1 beta-induced (1 ng/ml) prostaglandin E2 (PGE2) production from cultured endothelial cells by 82 +/- 2% (p < 0.001). Thus, this gene transfer strategy is the first to result in substantial transduction of both skeletal muscle capillary endothelium and fibers, sufficient to achieve pharmacologic levels of IL-1ra. Although no acute tissue injury or necrosis was observed, persistence of transgene expression in athymic rats suggests that loss of expression in normal rats was by an immune-mediated mechanism.

Adenoviridae↗

PKH26 and 125I-PKH95: characterization and efficacy as labels for in vitro and in vivo endothelial cell localization and tracking.

PKH26, a fluorescent cell label, and PKH95, a 125 I-radioactive cell label, are both potentially valuable endothelial cell labels because they bind irreversibly within cell membranes. These labels would be particularly well suited to tract transplanted endothelial cells in vivo. However, no previous studies documenting lack of transfer of the label to unlabeled endothelial cells, as well as the effect of the label on endothelial cell function, have been undertaken. The purpose of this study was to determine the optimal method of endothelial cell (EC) labeling with PKH26 and PKH95, whether significant to EC-to-EC transfer of the label occurs, the effects of these labels on EC proliferation and membrane function, and the feasibility of using these labels for long-term quantitative EC tracking in vivo. Canine ECs in confluent monolayers or in cell suspension were labeled by exposure to 1.0 or 5.0 microM PKH26 for 1, 3, or 5 min. Cell viability was determined by trypan blue exclusion. The percentage of cells labeled and their fluorescence intensity were determined in a fluorescent-activated cell sorter (FACS). Effect of the label on cell function was assessed by measuring EC proliferation rates as well as intercellular adhesion molecule (ICAM) expression before and after induction with tumor necrosis factor (TNF). To determine if transfer of the label occurs, both labeled and nonlabeled ECs were grown in coculture and subjected to FACS analysis. For in vivo cell tracking, doubly labeled ECs were injected into the femoral artery of rat hind-limbs, and whole-body tissue analysis was undertaken to determine labeled-EC distribution at 60 days. Endothelial cells were labeled with equal efficacy as monolayers or in suspension. Labeling had no effect on EC proliferation rates nor on TNF-induced upregulation of ICAM expression. Coculture experiments revealed no significant label transfer to nonlabeled ECs. In vivo cell tracking studies documented that 8% of label remained within the skeletal muscle capillaries at 60 days after injection. PKH26 and PKH95 labels incorporate stably into EC membranes, do not alter endothelial cell function, and provide a precise means for quantitative EC tracking and histologic localization both in vitro and in vivo. These labels should prove to be very useful for studies of endothelial cell biology and transplantation.

Animals↗

Tissue plasminogen activator increases canine endothelial cell proliferation rate through a plasmin-independent, receptor-mediated mechanism.

BACKGROUND: Tissue plasminogen activator (tPA) is elevated in cancer patients and is thought to promote tumor angiogenesis by facilitating endothelial cell migration through plasmin-mediated degradation of extracellular matrix. Due to the presence of an epidermal growth factor (EGF)-finger domain in the tPA A-chain and the existence of an endothelial cell (EC) receptor that binds this domain, it was hypothesized that tPA has a direct receptor-mediated effect on EC proliferation, independent of plasmin. METHODS AND RESULTS: Using cultured canine ECs, tPA (7.25 microg/ml, approximately 107 nM) increased proliferation as much as 50 and 170% in the absence and presence of growth factors, respectively. tPA-induced increases in EC proliferation occurred independent of plasmin generation, as the plasmin inhibitor, aprotinin (10 microg/ml) did not inhibit tPA-induced proliferation. However, tPA-induced proliferation was inhibited dose-dependently to a maximum of 78% using a monoclonal antibody against the tPA EGF-finger domain. This antibody, known to inhibit tPA binding to its receptor, did not inhibit tPA-induced plasmin generation. To investigate the role of potential signal transduction pathways, ECs were exposed to lavendustin A, a tyrosine kinase inhibitor, at 33.5 microM (IC50 for basic fibroblast growth factor). Lavendustin A did not inhibit tPA-induced EC proliferation. However, Rp-cAMP, an inhibitor of cAMP-dependent kinases, specifically inhibited tPA-induced EC proliferation in a dose-dependent manner (IC50 = 50.5 microM). Pertussis toxin at maximal concentrations for this system (0.5 ng/ml) did not inhibit tPA-induced EC proliferation. CONCLUSION: These results lend support to the hypothesis that tPA may have a direct receptor-mediated effect on EC proliferation and that this effect occurs independent of plasmin and may be dependent upon protein kinase A activity.

Animals↗