Search PubMed⌕ Search

Biomedical subjects

M A Golden

Publications and source records attributed to M A Golden.

At least 37 records · Page 2Linked to original sources

Native atherosclerosis and vein graft arterialization: association with increased urokinase receptor expression in vitro and in vivo.

Interaction of proteases with cell surface receptors may modulate cell adhesion, migration, invasion, and matrix degradation. Since the plasminogen activator system has been hypothesized to play a role in intimal thickening after various types of vascular injury, we first studied the expression of urokinase receptor (u-PAR) protein and mRNA by smooth muscle cells (SMC) grown in explant cultures from normal and diseased vessels. Using equilibrium binding studies with radiolabeled 125I-labeled single chain urokinase-type plasminogen activator (scu-PA), we determined that SMC cultured from atherosclerotic arteries expressed a higher maximal number of binding sites/cell (3.6 +/- 0.4 x 10(5) sites/cell vs. 2.1 +/- 0.3 x 10(5), +/- SEM, p < 0.05) with a similar affinity (Kd = 1.5 +/- 0.1 vs. 1.2 +/- 0.2 nM, p = ns). However, SMC subcultured from diseased saphenous vein grafts expressed the highest levels of u-PAR compared to SMC from normal saphenous vein (4.8 +/- 0.6 x 10(5) sites/cell vs. 1.6 +/- 0.9 x 10(5), +/- SEM, p < 0.05). Using binding studies and Northern analysis, we demonstrated a dose and time dependent upregulation of u-PAR protein and mRNA expression respectively in human SMC in response to serum stimulation. Using a rabbit specific u-PAR cDNA probe, we demonstrated a similar upregulation of u-PAR mRNA both in rabbit aortic SMC in culture in response to serum stimulation and up to a 20 fold increase in u-PAR mRNA in rabbit jugular veins in response to implantation as arterial grafts in vivo. Finally, to confirm that u-PAR mRNA is upregulated in human vessels after injury, we performed immunohistochemistry and in situ hybridization studies on coronary arteries, normal saphenous veins and saphenous veins from 10 weeks to 13 years after implantation as grafts. u-PAR mRNA was found mainly in the periadventitial microcirculation in normal veins, but was found to be upregulated in the neointima and media of thickened veins in both macrophages and smooth muscle cells. SMC near the internal elastic laminae in diseased coronary arteries appeared to express increased u-PAR mRNA. These data suggest that this increased expression of u-PAR may contribute to early lesion development.

Animals↗

Gene therapy.

Gene therapy for vascular disease is in the beginning stages. Each year investigators are increasing our understanding of the molecular and cellular biology of vascular disease and its complications. Our genes exert exquisite control over the expressed molecular pattern that results in biological function and pathology. Gene transfer techniques can be used to affect the pattern of gene expression. Gene therapy is a powerful tool that will allow specific manipulation of the genetic cascade that determines biological function. Gene transfer techniques should help to define the molecular mechanisms involved in vascular pathology, such as atherosclerosis and its complications. Currently, gene therapy has only reached clinical trials, but this new technology will likely play a major role in our treatment of vascular problems in the future. An understanding of the significance of this new technology is important for both health care providers and patients.

Animals↗

Pupil-involving third-nerve palsy and carotid stenosis: rapid recovery following endarterectomy.

We report a patient who presented with a painful pupil-involving third-nerve palsy. Cerebral angiography revealed a high-grade stenosis of the ipsilateral internal carotid artery with a 4-cm intraluminal thrombus. Following emergent carotid endarterectomy, the patient's partial third-nerve palsy resolved in 1 hour. A pupil-involving third-nerve palsy may be an unusual presentation of impending carotid occlusion.

Carotid Stenosis↗

Magnetic resonance angiography of the aortic arch.

Duplex ultrasound and magnetic resonance angiographic (MRA) studies are the principal noninvasive methods for evaluation of extracranial occlusive disease in patients at risk for stroke, but each has limited ability to diagnose aortic arch and arch vessel disease. Recent favorable reports of the nonnephrotoxic contrast agent Gadolinium (Gd) being used to enhance MRA images of the abdominal aorta prompted us to examine its utility for the aortic arch vessels. Prospectively, 28 patients with suspected carotid or arch vessel disease were imaged by contrast arteriographic examination and MRA + Gd of the aortic arch within 30 days of each other. One (for contrast arteriograms) or two (for MRA) blinded readers measured stenoses with the contrast arteriograms as the standard. A total of 196 arch vessels containing 58 stenoses and four occlusions (by arteriogram) were examined with each method. Interobserver agreement for interpretation of MRA studies was substantial (kappa = 0.68). MRA detected all anatomic anomalies (e.g., bovine arch). The correlation of MRA with arteriographic scans for arch vessel stenoses > 50% was sensitivity, 73% (readers 1 and 2); specificity, 98% (reader 1), 89% (reader 2); positive predictive value, 73% (reader 1), 89% (reader 2); negative predictive value, 98% (readers 1 and 2); accuracy, 97% (reader 1), 98% (reader 2). MRA + Gd is an accurate new noninvasive imaging method for detection of significant aortic arch disease. In its current state of development, however, it cannot obviate the need for contrast arteriographic examination.

Aorta, Thoracic↗

Antisense basic fibroblast growth factor gene transfer reduces neointimal thickening after arterial injury.

PURPOSE: To determine whether synthesis of endogenous basic fibroblast growth factor (bFGF) after arterial injury is critical to the intimal thickening response, intraluminal adenoviral gene transfer of an antisense bFGF (Ad.ASbFGF) transgene was used to inhibit the subsequent synthesis of bFGF protein after injury. METHODS: Sprague-Dawley rats underwent balloon catheter carotid artery injury and in vivo gene transfer. Isolated segments of rat common carotid artery were infected with an adenoviral vector encoding an antisense bFGF transcript at concentrations of 2 x 10(9), 1 x 10(10), or 1 x 10(11) pfu/ml. Control rats were treated with either a control adenovirus encoding the beta-galactosidase gene, (Ad.lacZ), at 1 x 10(10), or 1 x 10(11) pfu/ml, or phosphate-buffered saline solution (vehicle). Two weeks after injury the rats were killed and perfusion-fixed. Cross-sectional areas of the carotid arterial intima and media were measured by planimetry, and the intima/media ratio (I/M) was calculated for each vessel. RESULTS: The mean I/M for each Ad.ASbFGF group and controls were compared and the significance assessed by analysis of variance. At two weeks after injury, the highest dose of Ad.ASbFGF, 1 x 10(11) pfu/ml, resulted in a near total inhibition of thickening (I/M = 0.14 +/- 0.04, mean +/- SEM) when compared with phosphate-buffered saline solution alone (I/M = 0.99 +/- 0.07), or Ad.lacZ 1 x 10(10) pfu/ml (I/M = 1.01 +/- 0.10) control treatments (p < 0.01). A tenfold lower dose of Ad.ASbFGF, 1 x 10(10) pfu/ml, also caused significant reduction in intimal thickening (I/M = 0.39 +/- 0.07, p < 0.01). Treatment with 2 x 10(9) pfu/ml Ad.ASbFGF did not significantly limit intimal thickening (I/M = 0.72 +/- 0.12). CONCLUSIONS: Inhibition of bFGF synthesis in vivo using an antisense RNA strategy significantly inhibits intimal thickening after arterial balloon injury. This study suggests that continued bFGF synthesis contributes to intimal thickening after arterial injury, and that antisense bFGF may represent an effective strategy in limiting restenosis after angioplasty.

Adenoviruses, Human↗

Aortic dissection in a patient receiving chemotherapy for Hodgkin's disease--a case report.

Cancer chemotherapy is associated with a wide range of vascular toxicities, which may be related to endothelial cell damage by these agents. The authors describe a patient with Hodgkin's disease who developed an atypical aortic dissection while receiving MOPP/ABV chemotherapy (nitrogen mustard, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine). They would place aortic dissection on the list of potential vascular complications associated with antineoplastic agents.

Adult↗

The fate of bypass grafts to angiographically occult runoff vessels detected by magnetic resonance angiography.

PURPOSE: Magnetic resonance angiography (MRA) is a noninvasive vascular imaging technique that is more sensitive than contrast arteriography (CA) for the detection of patent distal runoff vessels. This technique has facilitated performance of MRA-directed bypass procedures for patients who were believed not to be bypass candidates because of the absence of a suitable target vessel on the preoperative CA. The fate of bypasses to these angiographically occult runoff vessels is unknown, however, and it has been proposed that patients with angiographically occult runoff may have aggressive occlusive disease, rendering bypass procedures ultimately futile. METHODS: Between April 1992 and February 1995, 212 autogenous vein infrageniculate bypasses were performed for limb-salvage indications, 22 (12%) to angiographically occult runoff vessels. Results of bypasses performed to angiographically occult vessels were compared with those of bypasses to CA-detected runoff vessels. Life-table analysis of graft-patency and limb-salvage rates was performed. RESULTS: The accuracy of the MRA-predicted patency of angiographically occult vessels was confirmed in every case by the operative findings. Life-table analysis revealed no significant difference in primary graft patency (p > 0.05) or limb-salvage (p > 0.05) rates between patients with bypasses to runoff vessels seen by MRA alone. At 35 months after surgery, the primary graft patency rate was 68% for bypasses to CA-detected vessel bypass and 67% for MRA-detected vessels. The limb salvage rate was 83% for CA-detected vessel bypass patients and 78% for patients with angiographically occult runoff. CONCLUSIONS: MRA can accurately identify patent runoff vessels not visualized by CA. Results of bypasses performed to angiographically occult runoff vessels are similar to those of bypasses performed to vessels detected by CA. MRA should be performed in patients in whom CA fails to reveal runoff vessels suitable for use in a limb-salvage procedure. The greater sensitivity of MRA may facilitate successful bypass surgery and improve the overall limb-salvage rate.

Aged↗

Inhibition of vein graft intimal and medial thickening by periadventitial application of a sulfated carbohydrate polymer.

PURPOSE: The purpose of this study was to determine whether the wall thickening observed in vein grafts after they were placed into the arterial circulation could be inhibited by periadventitial delivery of an insoluble sulfated polymer of beta-cyclodextrin (P-CDS) capable of tightly binding heparin binding growth factors. METHODS: Thirty-four New Zealand white rabbits underwent implantation of reversed autologous jugular vein interposition grafts in the common carotid artery and were randomized to receive either 20 mg P-CDS (n = 18) topically around the graft or no additional therapy (n = 16). Before being killed at 28 days, animals were given bromodeoxyuridine to assess smooth muscle cell proliferation. Histomorphometric analyses were performed after perfusion fixation. RESULTS: Compared to controls, treatment with P-CDS was associated with reduced mean intimal thickness (24 +/- 3 vs 38 +/- 4 microns; mean SEM, p < 0.01) and intimal area (0.25 +/- 0.03 vs 0.54 +/- 0.09 mm2; p < 0.01). There was also significantly less medial thickness in the P-CDS group (45 +/- 3 vs 63 +/-3, p < 0.001). There was no significant difference in intimal or medial smooth muscle cell proliferation between P-CDS-treated and control vein grafts at 28 days. The polymer persisted in the adventitia with a mild foreign body reaction. CONCLUSION: Periadventitial placement of P-CDS, a novel, insoluble, sulfated carbohydrate polymer, inhibits intimal and medial thickening of vein bypass grafts in this model of vein grafting. The persistence of P-CDS in vivo for prolonged periods, and the ease of topical application of P-CDS during vascular bypasses may have important implications for its future use in vascular surgery.

Administration, Topical↗

Breath-hold ultrafast three-dimensional gadolinium-enhanced MR angiography of the aorta and the renal and other visceral abdominal arteries.

OBJECTIVES: The objectives of this study were to develop and show the efficacy of a breath-hold ultrafast three-dimensional (3D) spoiled gradient-echo (SPGR) gadolinium-enhanced MR angiographic technique for imaging the aorta and the renal and other visceral arteries of the abdomen; and to compare breath-hold ultrafast 3D SPGR with two-dimensional (2D) time-of-flight (TOF) and non-breath-hold ultrafast 3D SPGR in the same patients. SUBJECTS AND METHODS: We prospectively studied the abdominal aorta and the renal and other visceral arteries 68 times in 63 consecutive patients with 2D TOF and ultrafast 3D SPGR MR angiography. Thirty-two patients had contrast angiography (n = 23) and/or surgery (n = 24) to serve as a gold standard. All MR imaging studies were performed on a 1.5-T scanner (General Electric Medical Systems, Milwaukee, WI) using an enhanced gradient system with maximum gradient strength of 2.3 gauss/cm reached in 150 microseconds. Axial 2D TOF parameters were: TR/TE, 33/5.5 msec; flip angle, 45 degrees; slice thickness, 2 mm; and no presaturation pulses. Coronal ultrafast 3D SPGR was performed before and after the i.v. administration of 40-60 cc of gadolinium. For the coronal ultrafast 3D SPGR, our parameters were: TR/TE, 4.8-7/1.1; flip angle, 60 degrees; 28-50 slices of 2.0-2.6 mm thickness; and acquisition time, 18-32 sec. Studies were read by a single radiologist [corrected] and were evaluated for the degree of stenosis in the renal, celiac, superior mesenteric, and inferior mesenteric arteries; any vascular anomalies (i.e., retroaortic renal veins and accessory renal or variant hepatic arteries) were noted. RESULTS: Breath-hold ultrafast 3D SPGR correctly identified 31 of 31 stenoses of the renal artery for a sensitivity, specificity, and accuracy of 100%. Two-dimensional TOF detected 23 of 31 renal artery stenoses for a sensitivity, specificity, and accuracy of 74%, 98%, and 87% respectively. Breath-hold ultrafast 3D SPGR underestimated two renal arteries as having severe osteal stenoses that were graded correctly by 2D TOF and by angiography as occlusions. Eight of nine (89%) accessory renal arteries were correctly identified with breath-hold ultrafast 3D SPGR: Two-dimensional TOF identified six of nine (67%). Breath-hold ultrafast 3D SPGR identified one accessory and two reconstituted renal arteries missed by 2D TOF and conventional contrast angiography that were confirmed at surgery. Ultrafast 3D SPGR and 2D TOF correctly identified 20 of 20 celiac, superior mesenteric, and inferior mesenteric artery osteal stenoses or occlusions for a sensitivity, specificity, and accuracy of 100%. Three Riolan's arcs were correctly identified by breath-hold 3D SPGR but were missed by 2D TOF: Forty of the 63 patients did not have conventional contrast angiography and were managed surgically (n = 9) or medically (n = 31) based on the results of the MR angiograms and clinical data. Breath-hold ultrafast 3D SPGR MR angiography correctly identified and graded 48 of 51 renal, celiac, superior mesenteric, and inferior mesenteric artery stenoses or occlusions. Two-dimensional TOF MR angiography correctly identified and graded 45 of 51 renal, celiac, superior mesenteric, and inferior mesenteric artery stenoses and occlusions. CONCLUSION: Breath-hold ultrafast 3D SPGR when combined with 2D TOF accurately identified and graded all (51 of 51) renal, celiac, superior mesenteric, and inferior mesenteric artery stenoses or occlusions.

Adolescent↗

Kasabach-Merritt coagulopathy complicating Klippel-Trenaunay-Weber syndrome in pregnancy.

BACKGROUND: Klippel-Trenaunay-Weber syndrome is a sporadic genetic syndrome characterized by localized hemangiomas, venous varicosities, and asymmetric osseous hypertrophy of the ipsilateral extremities. Most commonly seen in association with hemangiomas, Kasabach-Merritt syndrome is defined by the presence of thrombocytopenia and a consumptive coagulopathy. CASE: A 22-year-old primigravida with a prior diagnosis of Klippel-Trenaunay-Weber syndrome presented for genetic counseling and delivery management at 37 weeks' gestation. Large varicosities of the vulva required cesarean delivery. Multiple hemangiomas in the right lower quadrant of the abdomen necessitated the use of a left paramedian cutaneous incision. The patient subsequently developed Kasabach-Merritt syndrome and required the transfusion of blood products as well as heparin and aminocaproic acid therapy for her postoperative management. CONCLUSION: Klippel-Trenaunay-Weber syndrome in pregnancy is rare. The potential for a refractory coagulopathy presenting as Kasabach-Merritt syndrome should be considered in any patient who presents with extensive hemangiomas.

Apgar Score↗

Leech therapy in digital replantation.

This article presents a protocol for the perioperative care of patients undergoing digital replantation, which is the most common microsurgical procedure performed today. Venous congestion, a common complication of digital replantation, often has been treated through surgical exploration and creation of arteriovenous anastomosis. Leech therapy, however, is experiencing a resurgence among surgeons as an alternative method for treating venous congestion. This article discusses the anatomical, physiological, and clinical indications and methods of leech therapy in digital replantation.

Amputation, Traumatic↗

Sustained inhibition of intimal thickening. In vitro and in vivo effects of polymeric beta-cyclodextrin sulfate.

Intimal thickening after vascular injury may be modulated in part by heparin binding growth factors. We hypothesized that placement of a therapeutic polymer in the periadventitial space capable of tightly binding growth factors might alter the vascular response to injury. We first demonstrated that incubation of rat aortic smooth muscle cells with an insoluble, sulfated polymer of beta-cyclodextrin (P-CDS) was associated with a dose-dependent inhibition of proliferation induced by fetal calf serum, fibroblast growth factor-2 (FGF-2), platelet-derived growth factor BB, or epidermal growth factor. Preincubation studies of P-CDS with FGF-2 revealed a very rapid removal of mitogenic activity. Using radiolabeled FGF-2 (0.25 microg/ml), we observed a very rapid association rate (0.34 +/- 0.07 min-1, n=4) and a very slow dissociation rate (3.3 +/- 0.2 X 10(-7) min-1) at 37 degrees C, suggesting a high affinity interaction. Using both Transwell and linear under-agarose assays, we demonstrated a significant inhibition of random migration (chemokinesis) by P-CDS. Unsulfated polymeric beta-cyclodextrin (P-CD) had little if any of these effects, suggesting that the high negative charge density of P-CDS was important for the effects. Finally, rats undergoing carotid artery balloon injury were randomized to treatment with periadventitial P-CDS or no treatment, and were killed at 4 (n=20), 14 (n=59), and 88 d (n=14). Morphometric analysis demonstrated significant and sustained inhibition of intimal thickening in P-CDS-treated rats at 14 (P < 0.01) and 88 d (P < 0.05) using absolute intimal area or intima/media area ratios. No inhibition was seen in a group of rats treated with P-CD. In P-CDS-treated rats, bromodeoxyuridine labeling studies revealed fewer labeled smooth muscle cells in the intima at 14 d (P=0.01), while staining with Evans blue revealed enhanced late endothelial cell regrowth. Thus, periadventitially applied sulfated beta-cyclodextrin polymer, which can tightly bind heparin binding growth factors, inhibits intimal thickening in vivo in a sustained fashion without using an additional delivery system. These studies suggest that cellular processes mediated by heparin binding growth factors may be modulated by P-CDS.

Angioplasty, Balloon↗

Randomized prospective study of angioscopically assisted in situ saphenous vein grafting.

PURPOSE: A study was conducted to test the hypothesis that angioscopically assisted valve lysis and vein branch identification during in situ saphenous vein bypass would reduce technical causes of graft failure, local operative morbidity, and hospital stay. METHODS: Patients requiring primary bypass to an infrageniculate artery were randomly assigned to undergo in situ saphenous vein bypass with valvulotomy and branch identification either under angioscopic visualization with use of short intermittent incisions (scope) or under direct vision with use of a continuous incision (no scope). Data on operative details, morbidity, hospital length of stay, and graft patency were collected prospectively and compared. RESULTS: Fifty-nine patients were enrolled (32 scope, 27 no scope). There were no significant differences between study groups in the incidence of diabetes, claudication versus critical ischemia indications for surgery, or popliteal versus infrapopliteal location of distal anastomoses. Rates of wound complications (9.3% and 3.7%), early graft occlusion (6.2% and 7.4%), and mean postoperative hospital stay (8.0 and 8.6 days) were statistically similar for the scope and no scope groups, respectively. Differences in cumulative secondary patency rates at 48 months (79% scope, 91% no scope) were also insignificant. CONCLUSIONS: Use of angioscopy to assist with preparation of the in situ vein for infrageniculate grafting appears to have no impact on local operative morbidity, hospital length of stay, or midterm graft patency.

Aged↗

Magnetic resonance angiography of the aorta, iliac, and femoral arteries.

BACKGROUND: Successful management of patients with peripheral vascular disease requires detailed vascular imaging, usually performed by contrast arteriography. Recently, magnetic resonance angiography (MRA) has been shown to be a noninvasive technique with greater sensitivity than contrast arteriography for detecting distal runoff vessels in patients with peripheral arterial occlusive disease. However, to supplant the need for contrast arteriography and provide a completely noninvasive evaluation of patients with occlusive disease, accurate imaging of the inflow vessels and the runoff vessels is necessary. METHODS: We used both conventional arteriography and MRA in preoperative studies of the aorta, iliac, and femoral vessels of 47 patients. Conventional arteriography and MRA studies were compared for their ability to detect vessel patency and the presence of hemodynamically significant stenoses. Independent interventional plans were developed based on the information provided by each technique. The findings of conventional and MRA studies were verified by intraoperative arteriography or direct operative exploration. RESULTS: Results of the two studies were identical in 41 (87%) of 47 patients or 600 (98%) of 614 segments imaged. MRA accurately detected patent and occluded arterial segments (sensitivity 99.6%, specificity 100%, positive predictive value 100%, negative predictive value 98.6%) and hemodynamically significant stenoses. Therapeutic plans based on either MRA or conventional arteriography were identical for each patient. CONCLUSIONS: MRA provides comparable results to contrast arteriography in the proximal arterial system and superior results for imaging the distal vasculature. This noninvasive technique may replace contrast arteriography in a large number of patients in the future.

Adult↗

Infrageniculate bypass graft entrapment.

When failure of vein grafts is due to technical error it is usually observed in the early postoperative period. In this review we describe late failure of five bypass grafts as a result of entrapment of the vein graft caused by an improperly placed tunnel from the femoral to the popliteal artery. Vein graft entrapment may either produce no symptoms or eventually lead to limb ischemia. Pulses and pressures that vary with flexion and extension maneuvers should alert the clinician to the possibility of an entrapment syndrome. The characteristic arteriographic findings observed in these patients include an aberrant course of the vein graft outside the anatomic course of the popliteal artery and position-dependent compression of the graft. The ability of magnetic resonance angiography to demonstrate the arteriographic appearance of the graft as well as the precise location of the compression and to identify structures involved in the entrapment, make it a valuable noninvasive tool in the preoperative assessment of these patients. Treatment options include division of the gastrocnemius muscle, division of the vein graft, or replacement of the vein graft. Familiarity with vein graft entrapment should facilitate its recognition. Careful placement of bypass grafts along the anatomic course of the popliteal artery within the popliteal space will prevent this complication.

Aged↗

Inhibition of smooth muscle cell proliferation and experimental angioplasty restenosis by beta-cyclodextrin tetradecasulfate.

Heparin inhibits smooth muscle cell proliferation in vitro, a property that makes it potentially useful in preventing restenosis after angioplasty. Its utility in this setting is limited by the inability to use high doses (secondary to anticoagulant effects) and the need for subcutaneous administration. We tested the ability of beta-cyclodextrin tetradecasulfate (CDT), a nonanticoagulant synthetic heparin mimic, to inhibit smooth muscle cell proliferation in vitro and tested its efficacy when orally administered for the prevention of angioplasty restenosis in a rabbit atherosclerosis model. Vascular smooth muscle cells were cultured from rabbit aortas by the explant technique. Passaged cells were plated at low density in microtiter plates in the presence or absence of varying concentrations of heparin or CDT in culture medium containing 10% fetal calf serum. Using both 3H-thymidine incorporation and total protein assays, both heparin and CDT caused a similar dose-dependent inhibition of proliferation. We next tested the effect of orally administered CDT in the prevention of restenosis in focal femoral artery arteriosclerotic lesions created in hypercholesterolemic New Zealand White rabbits by air-dessication endothelial injury and subsequent peripheral angioplasty. Animals were followed up for 1 month and were fed normal chow supplemented by tap water with or without CDT. In animals receiving the highest concentration of CDT (2 mg/mL drinking water), the percentage of arterial cross-sectional area with intimal hyperplasia decreased from 50.5 +/- 1.7% (control) to 26.9 +/- 2.2% (p < 0.001), with the intimal/medial ratio being decreased from 1.4 +/- 0.4 to 0.5 +/- 0.2 (p = 0.056).(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty↗