Biomedical subjects

F A Weaver

Publications and source records attributed to F A Weaver.

At least 19 recordsLinked to original sources

PubMed2006

EphB4 receptor tyrosine kinase is expressed in bladder cancer and provides signals for cell survival.

We sought to evaluate the biological function of the receptor tyrosine kinase EphB4 in bladder cancer. All of the nine bladder cancer cell lines examined express EphB4 and the receptor could be phosphorylated following stimulation with its cognate ligand, EphrinB2. Out of the 15 fresh bladder cancer specimens examined, 14 expressed EphB4 with a mean sevenfold higher level of expression compared to adjacent normal urothelium. EphB4 expression was regulated by several mechanisms: EPHB4 gene locus was amplified in 27% tumor specimens and 33% cell lines studied; inhibition of EGFR signaling downregulated EphB4 levels; and forced expression of wild-type p53 reduced EphB4 expression. EphB4 knockdown using specific siRNA and antisense oligodeoxynucleotides molecules led to a profound inhibition in cell viability associated with apoptosis via activation of caspase-8 pathway and downregulation of antiapoptotic factor, bcl-xl. Furthermore, EphB4 knockdown significantly inhibited tumor cell migration and invasion. EphB4 knockdown in an in vivo murine tumor xenograft model led to a nearly 80% reduction in tumor volume associated with reduced tumor proliferation, increased apoptosis and reduced tumor microvasculature. EphB4 is thus a potential candidate as a predictor of disease outcome in bladder cancer and as target for novel therapy.

Base Sequence↗

PubMed2001

Cervical vascular injuries: carotid and jugular venous injuries.

This article explores the management of carotid arterial injuries, detailing the historical evolution for the management of these injuries and delineating techniques for cerebral perfusion and preservation with shunts. It discusses the role of autogenous versus synthetic grafts in the management of these injuries and the issue of vascular complications and potential pitfalls. Jugular venous injuries are addressed also, with emphasis on the controversies of primary repair versus ligation.

Carotid Artery Injuries↗

PubMed2001

Dual cell seeding and the use of zymogen tissue plasminogen activator to improve cell retention on polytetrafluoroethylene grafts.

OBJECTIVE: The purpose of this study was to enhance the retention of seeded endothelial cells (EC) on prosthetic vascular grafts. Dual-layer EC and smooth muscle cell (SMC) seeding and gene transfer of a zymogen tissue plasminogen activator gene (tPA) into seeded EC were studied. METHODS: Polytetrafluoroethylene (PTFE) grafts were precoated with fibronectin, seeded with SMC followed by EC a day later, and then, 24 hours later, exposed to an in vitro flow system for 1 hour. Cell retention rates were determined for grafts seeded with EC only, a dual layer of EC on top of SMC, EC transduced with wild-type tPA, and EC transduced with zymogen tPA. RESULTS: Seeding efficiency of PTFE pretreated with fibronectin was 260 +/- 8 cell/mm(2). After exposure to flow, only 39% +/- 14% of the EC were retained when EC were seeded alone, whereas 73% +/- 22% of EC remained on grafts when EC were seeded on top of SMC (P <.001, n = 10). The enzyme activity of a mutant zymogen tPA in absence of fibrin was 14 +/- 1 IU/mL, which is 3.6-fold lower than that in the presence of fibrin (50 +/- 19 IU/mL), whereas fibrin has no effect on the wild-type tPA activity. EC expressing a high level of wild-type tPA had a lower retention rate (37%) when compared with normal EC (45%). EC expressing the mutant zymogen tPA had an improved retention rate (54%, P =.001, n = 10) in absence of fibrin, whereas its retention rate was reduced to 43% when the cells were exposed to fibrin. CONCLUSION: SMC seeded between EC and PTFE improves EC retention in vitro. Transduction of zymogen tPA increases thrombolytic ability of seeded cells with less adverse impact on cell retention than wild-type tPA.

Blood Vessel Prosthesis↗

PubMed2000

The use of colorflow duplex scanning to detect significant renal artery stenosis.

The purpose of this study was to review our institutional experience with colorflow duplex scanning in detecting significant renal artery stenosis and to validate the criteria used: renal artery peak systolic velocity (PSV) >/=200 cm/sec and renal-to-aortic peak systolic ratio (RAR) >/=3.5. The results of renal artery duplex and arteriography in 58 patients (107 kidneys) who underwent both exams were reviewed. Arteriography revealed 32 main renal arteries with >/=60% stenosis. The PSV criterion detected 29, for a sensitivity of 91%, specificity of 75%, positive predictive value (PPV) of 60%, negative predictive value (NPV) of 95%, and accuracy of 79%. Using RAR >/=3.5 provided a sensitivity of 72%, specificity of 92%, PPV of 79%, NPV of 88%, and accuracy of 86%. In a subset of 36 kidneys that had hilar scans, the criteria of acceleration time (AT) >/=100 cm/sec and index (AI) </=3.78 kHz/sec were evaluated. The AT and AI yielded sensitivity of 50% and 36%, specificity of 86% and 100%, PPV of 70% and 100%, NPV of 73% and 71%, and accuracy of 72% and 75%, respectively. Colorflow duplex scanning is clinically useful in screening for hemodynamically significant renal artery stenosis. The renal artery PSV criterion is highly sensitive, with a high NPV that obviates the need for arteriography in most cases of a negative duplex. The criteria of RAR, AT, and AI are of less value.

Adult↗

PubMed2000

Human macrovascular endothelial cells: optimization of culture conditions.

The purpose of this study is to identify optimal culture conditions to support the proliferation of human macrovascular endothelial cells. Two cell lines were employed: human saphenous vein endothelial cells (HSVEC) and human umbilical vein endothelial cells (HUVEC). The influence of basal nutrient media (14 types), fetal bovine serum (FBS), and mitogens (three types) were investigated in relation to cell proliferation. Additionally, a variety of extracellular matrix (ECM) substrate-coated culture dishes were also tested. The most effective nutrient medium in augmenting cell proliferation was MCDB 131. Compared to the more commonly used M199 medium, MCDB 131 resulted in a 2.3-fold increase in cell proliferation. Media containing 20% FBS increased cell proliferation 7.5-fold compared to serum-free media. Among the mitogens tested, heparin (50 microg/ml) and endothelial cell growth supplement (ECGS) (50 microg/ml) significantly improved cell proliferation. Epithelial growth factor (EGF) provided no improvement in cell proliferation. There were no statistical differences in cell proliferation or morphology when endothelial cells were grown on uncoated culture plates compared to plates coated with ECM proteins: fibronectin, laminin, gelatin, or collagen types I and IV. The culture environment yielding maximal HSVEC and HUVEC proliferation is MCDB 131 nutrient medium supplemented with 2 mM glutamine, 20% FBS, 50 microg/ml heparin, and 50 microg/ml ECGS. The ECM substrate-coated culture dishes offer no advantage.

Animals↗

PubMed1999

Retroviral vector-mediated transfer and expression of human tissue plasminogen activator cDNA in bovine brain endothelial cells.

OBJECTIVES: Gene transfer of thrombolytic enzymes to vascular endothelial cells may influence the kinetics of intravascular thrombosis. This study defines the potential for gene transfer of tissue plasminogen activator (tPA) into bovine brain endothelial cells (BBEC). METHODS: The retroviral vectors derived from murine leukemia virus (MuLV) were used to transfer human tPA cDNA to BBEC. The tPA activity, tPA antigen and tPA inhibitor 1 (PAI-1) antigen were determined in the supernatant of transduced (BBEC/tPA) cell cultures by an immunoassay. RESULTS: The tPA antigen and enzymatic activity in cell culture supernatants of BBEC/tPA transduced cells were 75 ng/ml and 14 IU/ml after 4 days, that was 25 and 28-fold higher compared to the respective values in control cells. The PAI-1 antigen was not affected by tPA cDNA transfer. The Western blot assay of cell lysates confirmed that the majority of tPA in BBEC/tPA transduced cells was in the form of free tPA. While the maximal transduction efficiency of BBEC with an amphotropic MuLV vector was about 15%, a MuLV pseudotyped with vesicular stomatitis virus G glycoprotein envelope achieved high > 90% maximal transduction efficiency. CONCLUSIONS: The fibrinolytic activity of brain endothelial cells can be enhanced by transferring human tPA cDNA. These findings provide an initial step in implementation of future studies that investigate the use of this technology as an adjunctive treatment for cerebrovascular disease.

Animals↗

PubMed1998

Cocaine-induced thrombosis of common iliac and popliteal arteries.

Cocaine-induced thrombosis has been reported in the literature; however, its mechanism is not fully understood. Most cases are of small caliber vessels, such as the coronaries and cerebral vasculature. We report a case of a 36-year-old man with signs and symptoms of acute arterial insufficiency in his right lower extremity. At angiography, the right common iliac artery and the popliteal artery were occluded. The patient was successfully treated with thrombolytic therapy. Cocaine-induced thrombosis should be suspected in a patient with history of cocaine abuse who presents with acute arterial insufficiency in an extremity, without an identifiable source.

Acute Disease↗

PubMed1998

Diagnosis and management of penetrating vascular trauma and the injured extremity.

Early diagnosis and timely treatment of extremity vascular injuries are essential if limb salvage and limb function are to be optimized. Careful and repeated clinical examination and ankle/brachial doppler indices are pivotal for early diagnosis. Routine arteriography for proximity injury is neither cost effective nor clinically indicated and minimal non-occlusive arterial injuries do not require vascular repair. An algorithm for the diagnostic evaluation and treatment of patients with penetrating extremity trauma is presented. The early diagnosis of compartment syndrome is stressed.

Algorithms↗

PubMed1998

Combined carotid endarterectomy and coronary artery bypass grafting in asymptomatic carotid artery stenosis.

The role of combined carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG) in patients with severe asymptomatic carotid artery disease and concurrent symptomatic coronary artery disease is controversial. The objective of this report is to investigate the safety of combined CEA/CABG. The medical records of 30 patients who underwent combined CEA/CABG for coexistent asymptomatic carotid and symptomatic coronary artery occlusive disease were reviewed. All patients were scheduled for either elective or urgent myocardial revascularization due to their symptomatic coronary artery disease. Color-flow duplex scanning identified internal carotid artery stenosis of 80 to 99 per cent in 28 patients (93%) and 50 to 79 per cent in 2 patients (7%). Seventeen patients (57%) were male. The mean age was 64 +/- 10 years (range, 42-84 years). Contralateral internal carotid artery occlusion was present in four patients. Severe left main coronary artery disease was present in 12 patients (40%) and 7 patients (23%) had an ejection fraction of less than 50 per cent. There were no perioperative deaths or strokes. One patient suffered a myocardial infarction on postoperative day 1. This study demonstrates the safety of combined CEA/CABG for coexistent coronary and asymptomatic carotid disease. Using this surgical approach for critical coexistent disease may minimize the incidence of perioperative cerebrovascular complications in patients undergoing CABG.

Adult↗

PubMed1998

Changing perspectives in the diagnosis of peripheral vascular trauma.

The diagnosis of peripheral vascular trauma has undergone significant evolution in the last two decades. A minority of patients with arterial trauma present with classic findings that make the diagnosis obvious. However, the diagnosis of occult arterial injuries is more challenging, and it is for this group that the diagnostic algorithm has changed most significantly. Because of the low yield of routine operative exploration and routine arteriography to evaluate potential injury to vessels in proximity to penetrating wounds, many authors now recommend the selective use of arteriography or other diagnostic modalities based on the results of clinical examination and noninvasive pressure determinations. This article reviews the evidence in support of such a selective approach to the diagnosis of arterial injuries.

Algorithms↗

PubMed1997

The practical implications of recent trials comparing thrombolytic therapy with surgery for lower extremity ischemia.

UNLABELLED: Catheter-based thrombolysis for lower extremity ischemia is a well-accepted and frequently used technique. Three prospective randomized trials, Rochester, STILE, and TOPAS, which compared thrombolytic therapy with traditional surgical revascularization for lower limb ischemia, have recently been published. METHODS: These three trials are reviewed with the intent of assessing the relative of value of thrombolytic therapy and surgical revascularization for lower limb ischemia. RESULTS: As an initial therapy, thrombolysis reduces the magnitude of any subsequent surgical procedure in approximately 40% to 60% of patients. However, recurrent ischemia is frequent, and the subsequent need for surgical revascularization is common for any native artery occlusion or chronic (> 14 days) bypass graft occlusion. In the patient with an acute bypass graft occlusion, the incidence of recurrent ischemia is less and limb salvage at 1 year is enhanced when treated initially by thrombolysis. A possible survival benefit after thrombolysis was suggested in the Rochester trial and in the STILE trial for diabetics with femoral-popliteal occlusions. CONCLUSIONS: Surgical revascularization remains the optimal therapy for most patients with lower limb ischemia. However, thrombolysis as an initial therapy does reduce the magnitude of any subsequent surgical procedure and provides improved limb salvage for patients with acute bypass graft occlusions.

Arterial Occlusive Diseases↗

PubMed1997

Vascular complications of thoracic outlet syndrome.

Vascular complications of thoracic outlet syndrome are uncommon but may result in significant long-term disability. This report documents a retrospective review of 17 such patients. Ten patients presented with acute onset of upper extremity swelling and axillosubclavian vein thrombosis. One patient presented with chronic, intermittent arm swelling and subclavian vein stenosis. Three patients presented with acute symptoms of upper extremity emboli, and three presented with chronic arm claudication. Cervical ribs were discovered in four patients with arterial symptoms and in no patients with venous symptoms. All ten patients with acute venous thrombosis underwent successful thrombolysis, with venous stenosis uncovered in 8. Thrombolysis was also performed for two patients with arterial emboli. All 17 patients underwent surgical decompression of the thoracic outlet, 16 via a supraclavicular approach and one via a transaxillary approach. One subclavian arteriotomy with endarterectomy and one resection of a subclavian artery aneurysm were performed at the time of decompression. Repeat venography after decompression demonstrated persistent venous stenosis in one patient that was treated with balloon angioplasty and stenting. After a mean of 22 months' follow-up, 12 patients had no residual symptoms, and 5 had experienced significant improvement of symptoms. In conclusion, a combined approach of thrombolysis and surgical decompression of the thoracic outlet provides a salutary outcome in a majority of patients.

Acute Disease↗

PubMed1996

A prospective study of carbon dioxide-digital subtraction vs standard contrast arteriography in the evaluation of the renal arteries.

OBJECTIVE: To compare carbon dioxide-digital subtraction arteriographic (CO2-DSA) images of renal artery anatomy with standard iodinated contrast arteriographic (ICA) images. DESIGN: One hundred patients with vascular disease who required abdominal aortography were evaluated by both CO2-DSA and ICA modalities. Two blinded readers interpreted arteriograms for the degree of renal artery stenosis, and a third reader was employed to resolve differences in reader interpretations. SETTING: University medical center. MAIN OUTCOME MEASURES: The sensitivity, specificity, negative predictive value, positive predictive value, and accuracy were calculated for the ability of CO2-DSA to demonstrate a 60% or greater stenosis of the main renal artery; kappa values for CO2-DSA and ICA were calculated to assess intraobserver variability. RESULTS: Of the 200 main renal arteries imaged, 17 (9 by means of CO2-DSA), 8 means of ICA) were eliminated because of inadequate visualization of the renal artery. In identifying a renal artery stenosis of 60% or greater, CO2-DSA had a sensitivity of 0.83, specificity of 0.99, positive predictive value of 0.94, and negative predictive value of 0.98. The overall accuracy was 0.97. The kappa was 0.75 for CO2-DSA and 0.70 for ICA, hence, the variation in the interpretations of CO2-DSA and ICA were comparable. CONCLUSION: Images by means of CO2-DSA accurately reflect pathologic changes in renal arteries and are thus useful in the diagnosis of clinically occult occlusive renal artery disease in patients at risk of contrast medium-related nephrotoxicity.

Adult↗

PubMed1996

Penetrating trauma of the internal carotid artery.

OBJECTIVE: To assess management of penetrating internal carotid artery (ICA) injuries. DESIGN: Retrospective review of institutional protocol. SETTING: Level 1 trauma center in a major urban area. PATIENTS: Sixty-one patients with penetrating ICA injuries. INTERVENTIONS: In the period 1975 to 1987 (group 1; n = 36), management was based on individual surgeons' preferences. Between 1988 and 1995 (group 2; n = 25), an algorithm was employed: (1) hemodynamically stable patients with suspected ICA injuries underwent a diagnostic angiography; (2) surgically accessible injuries were reconstructed regardless of neurologic status with 2 exceptions: (a) neurologically intact patients with ICA occlusion were treated by anticoagulation and mild pharmacological hypertension and (b) minimal nonocclusive injuries were managed nonoperatively and followed up by serial angiography or duplex ultrasonography; and (3) heparinization, shunting, and completion angiography were employed. MAIN OUTCOME MEASURES: Neurologic status at admission and discharge were compared by the Fisher exact test. RESULTS: In group 1, 24 patients (67%) presented neurologically intact, and 12 (33%) with a deficit. Sixteen injuries were managed nonoperatively, 14 were repaired, and 6 were ligated. At discharge 6 (17%) were improved, 24 (66%) were unchanged, 6 (17%) were worse. Four patients (11%) died of cerebrovascular causes. In group 2, 19 patients (76%) presented neurologically intact, and 6 (24%) with a deficit. Eleven injuries were managed nonoperatively, 12 were repaired, and 2 were ligated. A death occurred in a patient who arrested, was admitted to the hospital in a coma, and died before ICA repair. CONCLUSIONS: Neurologic outcome after ICA injury is enhanced by an algorithm predicated on the liberal use of angiography, a predefined surgical approach, and selective observation.

Adolescent↗

PubMed1996

Cardiac evaluation of the diabetic patient prior to peripheral vascular surgery.

The benefit of preoperative cardiac evaluation in the diabetic patient undergoing peripheral vascular surgery is uncertain. To investigate this issue we performed a retrospective review of 192 procedures performed in diabetic patients for chronic lower extremity arterial occlusive disease. The incidence of adverse postoperative cardiac events was determined, as well as its association with several preoperative factors including symptoms of coronary artery disease (CAD), extent and results of preoperative noninvasive cardiac evaluation, and operative site (aorta vs. lower extremity). The overall death and cardiac complication rates were 10.2% for lower extremity and 25.7% for aortic procedures (p = 0.02). For myocardial infarction and cardiac death alone, the rates were 5.1% and 5.7%, respectively (p > 0.10). Although a history of symptomatic CAD predicted the occurrence of any cardiac complication (28.3% vs. 8.2% [p < 0.01] for the aortic and lower extremity revascularization groups combined), no factor was found to be associated with the occurrence of myocardial infarction and cardiac death alone. In patients with a history of symptomatic CAD, there was no significant difference in the incidence of complications whether or not preoperative noninvasive cardiac testing was performed (28.1% vs. 28.6%, p > 0.10) or, if testing was performed, if the results were abnormal or normal (35.3% vs. 20.0%, p > 0.10). Similar results were obtained in patients with no history of symptomatic CAD. In summary, this retrospective review of our experience with noninvasive evaluation to detect CAD in diabetic patients undergoing peripheral vascular surgery failed to show any benefit in terms of reducing the incidence of postoperative cardiac events.

Aged↗

PubMed1996

Intraoperative color duplex scanning for infrainguinal vein grafts.

We compared the findings of intraoperative color duplex scanning and completion arteriography in patients undergoing infrainguinal vein bypasses to identify hemodynamic abnormalities that could result in a predisposition to early or late graft failure. We reviewed the records of 72 patients who underwent 81 vein bypass graft procedures. Three intraoperative diagnostic methods were used. In 28 procedures (group I) both color duplex and completion arteriography were used, in 21 procedures (group II) only color duplex was used, and in 26 procedures (group III) only completion arteriography was used. Grafts were followed using a duplex surveillance protocol for a mean interval of 16.1 months. Nine grafts in group I showed an abnormality on the duplex scan but not on the completion arteriogram. Seven grafts had a peak systolic velocity (PSV) greater than 200 cm/sec and two had a PSV less than 45 cm/sec. These findings led to six immediate repairs, one early revision, and two late revisions. Arteriography demonstrated additional defects in two procedures but repairs were not performed. In group II duplex scans showed an abnormality in eight procedures (seven grafts with PSV 200 to 250 cm/sec and one graft with a retained valve) resulting in three immediate repairs and five late revisions. In the remaining 13 procedures in group II, duplex scans were normal and no revisions were required during follow-up. In group III defects were detected by arteriography in four procedures (> 50% stenosis in three grafts and one arterial spasm) leading to three immediate repairs. In the remaining 22 studies arteriograms were interpreted as normal; however, seven of these grafts required late revisions. Our data suggest that grafts that appear normal on intraoperative duplex scans are not likely to develop a stenosis requiring revision. Intraoperative duplex ultrasound may be superior to completion arteriography.

Adult↗

PubMed1996

Syme amputation: results in patients with severe forefoot ischemia.

Since 1980, 35 patients (age range 40-77 years) with severe forefoot ischemia have undergone a unilateral Syme amputation. Thirty-one patients (89%) were diabetic. The indication for amputation was either extensive forefoot gangrene or ulceration too advanced for a digital or transmetatarsal amputation. Twenty-two amputations (63%) were immediately preceded by either percutaneous transluminal angioplasty (four) or a bypass procedure to the popliteal artery (five) or an infrapopliteal artery (13). Primary healing occurred in 19 (86%) of 22 amputations immediately preceded by revascularization and in 10 (77%) of 13 limbs undergoing amputation alone. Twenty-eight (97%) of the 29 patients with successful primary healing were successfully rehabilitated. Rehabilitation rendered 13 patients fully ambulatory, 15 ambulatory with intermittent use of a walker or cane and one unable to walk. At follow-up of four months to 13 years (mean 42 months), the cumulative ambulatory rate at 1, 3, and 5 years was 92, 80 and 80%, respectively. Syme amputation allows a return to a functional ambulatory status in a high percentage of patients with severe forefoot ischemia. These findings suggest that Syme amputation is an acceptable option in dysvascular patients with severe forefoot ischemia.

Adult↗

PubMed1996

Results of a prospective, randomized trial of surgery versus thrombolysis for occluded lower extremity bypass grafts.

PURPOSE: The purpose of this study was to prospectively evaluate the treatment of patients with occluded lower extremity bypass grafts, comparing surgical revascularization with catheter-directed thrombolysis. MATERIALS AND METHODS: One hundred twenty-four patients (68% male and 32% female) with lower limb bypass graft occlusion (46 autogenous and 78 prosthetic) were prospectively randomized to surgery (n = 46) or intra-arterial catheter-directed thrombolysis (n = 78) with recombinant tissue plasminogen activator (rt-PA) 0.1 mg/kg/h modified to 0.05 mg/kg/h for up to 12 hours, or urokinase (UK) 250,000 U bolus followed by 4,000 U/min for 4 hours, then 2,000 U/min for up to 36 hours. A composite clinical outcome including death, amputation, ongoing/recurrent ischemia, and major morbidity was analyzed on an intent-to-treat basis at 30 days and 1 year. RESULTS: The average duration of graft occlusion was 34.0 days, with 58 (48%) presenting with acute ischemia (0 to 14 days) and 64 (52%) with chronic ischemia (> 14 days). Thirty-nine percent randomized to lysis failed catheter placement and required surgical revascularization. Overall, there was a better composite clinical outcome at 30 days (P = 0.023) and 1 year (P = 0.04) in the surgical group compared with lysis, due predominately to a reduction in ongoing/recurrent ischemia, most notable in autogenous grafts. However, following successful catheter placement, patency was restored by lysis in 84%, and 42% had a major reduction in their planned operation. One-year results of successful lysis compared favorably with the best surgical procedure, which was new graft placement. Acutely ischemic patients (0 to 14 days) randomized to lysis demonstrated a trend toward a lower major amputation rate at 30 days (P = 0.074) and significantly at 1 year (P = 0.026) compared with surgical patients, while those with > 14 days ischemia showed no difference in limb salvage but higher ongoing/recurrent ischemia in lytic patients (P < 0.001). Patients with occluded prosthetic grafts had greater major morbidity than did those with occluded autogenous grafts (P < 0.02). CONCLUSIONS: Proper catheter positioning currently limits the potential of catheter-directed thrombolysis for lower extremity bypass graft occlusion. Patients with graft occlusion > 14 days have a significantly better outcome when treated surgically, with a new bypass being the best surgical option. However, in patients with acute limb ischemia (< 14 days) successful thrombolysis of occluded lower extremity bypass grafts improves limb salvage and reduces the magnitude of the planned surgical procedure. Patients with occluded prosthetic grafts suffer more major morbid events compared with occluded autogenous grafts.

Female↗