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Biomedical subjects

K Ouriel

Publications and source records attributed to K Ouriel.

At least 73 records · Page 4Linked to original sources

A multi-modal approach to the management of bypass graft failure.

Bypass graft failure is an unsolved problem in the contemporary treatment of peripheral arterial occlusion. Thrombolysis of a failed bypass graft is performed with instillation of plasminogen activators directly into the substance of the thrombus. Thrombolytic techniques can restore the bypass graft to its pre-occlusive state, clearing the inflow and outflow tracts of propagated thrombus and unmasking the causative lesion responsible for graft occlusion. Open surgery, or an endovascular modality, can then be employed to directly address these lesions. Recent randomized trials have demonstrated the safety and efficacy of a thrombolytic treatment strategy when the graft occlusion is acute, that is, when the patient presents within 2 weeks of the event. The appropriate management of the patient with an acutely occluded bypass graft includes thrombolysis, endovascular modalities and open surgery, employed in conjunction, to improve patient outcome over that observed with an immediate operation alone.

Angiography↗

Noninvasive diagnosis of upper extremity vascular disease.

The relative rarity of vascular disorders of the arm accounts for unfamiliarity with upper extremity diagnostic testing on the part of even experienced vascular clinicians. Understanding the wide variety of noninvasive tests is imperative if one is to appropriately diagnose and treat these disorders. The diagnosis and localization of arterial occlusive disease is dependent on the use of Doppler-derived arterial pressures, which may be measured serially from the upper arm to the digits. Plethysmographic digital waveforms can be used as an aid in the diagnosis of vasospastic disorders as well as in the assessment of therapy. Similarly, provocative testing with cold stimulation can assist in the diagnosis of Raynaud's and other vasospastic disorders. The use of duplex ultrasonography for venous occlusion, although not as accurate as when used for lower extremity problems, can be a useful aid in the diagnosis of upper extremity venous thrombosis. Symptoms associated with the thoracic outlet syndrome can be evaluated and confirmed noninvasively, measuring Doppler pressures and gauging venous outflow obstruction while the patient performs a variety of positional maneuvers. A thorough knowledge of upper extremity noninvasive tests will provide the clinician with confidence in the objective assessment of upper extremity vascular disease.

Arm↗

Acute lower limb ischemia: determinants of outcome.

BACKGROUND: Previous studies have documented high rates of morbidity and death after acute peripheral arterial occlusion. To date, however, few studies have identified parameters predictive of successful therapy. METHODS: The Thrombolysis or Peripheral Arterial Surgery Trial of intraarterial recombinant urokinase or immediate operation for acute lower extremity arterial occlusion provided data on 544 patients randomized at 113 centers. A Cox proportional hazards multifactor analysis was performed to identify those main effects predictive of amputation-free survival and to document any baseline variables useful in deciding whether a patient would be treated best initially with thrombolysis or operation. RESULTS: Of 28 variables analyzed, eight main effects were predictive of amputation-free survival. These included two demographic factors: white race (risk ratio [RR] = 1.75; p = 0.003) and younger age (RR = 1.015; p = 0.046). Comorbidities comprised four of the main effects: history of central nervous system disease (RR = 1.726; p = 0.005), history of malignancy (RR = 1.615; p = 0.024), congestive heart failure (RR = 2.202; p < 0.001), or low body weight (RR = 1.007 per pound; p = 0.006). The severity of the process was also predictive, as gauged by the presence of skin color changes (RR = 1.585, p = 0.007) or pain at rest (RR = 0.503; p = 0.003). All eight effects were similar in the two treatment groups; none of these variables predicted improved outcome with one form of initial therapy over the other (i.e., there was no therapy-by-variable interaction). The length of occlusion, however, predicted whether a patient would fare better with thrombolysis or operation. With a threshold occlusion length of 30 cm, the RR for longer occlusions to shorter occlusions was 43% better in patients who received thrombolysis, whereas the situation was reversed for those who were randomized to operation. CONCLUSIONS: A variety of baseline variables can be identified that are predictive of outcome after treatment for acute lower extremity ischemia. In addition, the length of the occlusive process appears to predict whether a patient will be best served with thrombolysis or operative intervention; longer occlusions appear to respond best with an initial thrombolytic strategy.

Acute Disease↗

A condemnation of subcutaneous fasciotomy.

Controversy exists regarding the indications and methods for lower-extremity fasciotomy. Two recent cases at our institution in which recurrent, acute limb-threatening ischemia occurred despite adequate fascial division have convinced us that in certain situations subcutaneous fasciotomy is clearly inadequate. In both patients, both of whom were young, intact healthy skin between the lower extent of the incision and the malleolus acted as a tourniquet, causing recurrent compartment syndrome as reperfusion edema occurred after initial repair. We believe that therapeutic fasciotomy in young patients with relatively noncompliant skin should include division of skin from the knee to the ankle on at least one side to prevent a tourniquet effect by intact skin at the ankle.

Adolescent↗

Impact of inflow reconstruction on infrainguinal bypass.

PURPOSE: This study assessed whether multisegmental disease that is severe enough to require an inflow procedure adversely affects infrainguinal bypass patency, limb salvage, or patient survival rates. METHODS: The records of 495 patients who underwent 551 infrainguinal bypass grafting procedures were reviewed. Saphenous vein and prosthetic grafts were evaluated separately. Graft patency rates, patient limb salvage rates, and patient survival rates in those grafts that arose from a reconstructed inflow source were compared with those that arose from normal, nonreconstructed inflow sources. When grafts had either hemodynamic failure or occlusion, the cause of failure was identified. RESULTS: Four-year primary patency rates in vein grafts that arose from a reconstructed inflow sources were lower than those in grafts that arose from nonreconstructed inflow sources (41% vs 54%; p = 0.006). Assisted primary patency rates and secondary patency rates, however, were similar (62% vs 74% and 64% vs 77%, respectively). The 4-year primary patency rate (45% vs 55%), assisted primary patency rate (60% vs 60%), and secondary patency rate (60% vs 61%) in prosthetic grafts did not vary based on inflow source. The most common cause of graft failure was inflow failure, except in the vein grafts that did not require an inflow procedure, in which the most common cause of failure was graft failure. Inflow failure occurred in 24% and 22% of the vein and prosthetic grafts with multisegmental disease, respectively, but in only 7% (p < 0.001) and 10% (p < 0.05), respectively, of those that arose from normal nonreconstructed inflow. The presence of an inflow procedure did not affect limb salvage rates or patient survival rates, regardless of graft material. CONCLUSIONS: Long-term patency rates, patient limb salvage rates, and survival rates in patients with a reconstructed inflow source were similar to those of patients with a normal nonreconstructed inflow. A major cause of occlusion is inflow failure, and this occurs in a greater proportion of patients with multisegmental disease. These patients, in particular, may benefit from patient surveillance to screen for progression of their inflow disease and to allow for intervention before infrainguinal graft occlusion.

Aged↗

Fate of the proximal aortic cuff: implications for endovascular aneurysm repair.

PURPOSE: Long-term success of endoluminally placed grafts for exclusion of abdominal aortic aneurysms (AAAs) relies on secure fixation at the proximal and distal cuffs and, as such, assumes that the fixation sites will not dilate over time. Data regarding this issue, however, are not yet available. This study was performed to evaluate the region of the proximal anastomosis in patients many years after having undergone conventional AAA repair to determine the potential for late dilatation after placement of an endoluminal device. METHODS: Three hundred forty-six patients underwent repair of an infrarenal AAA at our institution between January 1985 and December 1990. Of 97 eligible living patients, 33 both had their original CT scans available and underwent repeat scanning at a mean of 88.6 +/- 23.8 months (mean +/- SD; range, 40 to 134 months) after repair. RESULTS: The overall 5-year survival rate was 73%. The mean preoperative infrarenal aortic cuff diameter by CT scan was 24.5 +/- 3.7 mm (range, 19 to 33 mm). At an average of 89 months after repair, the mean infrarenal aortic diameter increased 4.3 mm to 28.8 +/- 7.7 mm (range, 20 to 52 mm; p = 0.0004 by t test). The proximal cuff at this time measured 30 mm or more in 11 patients (33%), and as early as 6 years after operation three of the seven patients (43%) scanned within this time period had cuffs that were dilated to 30 mm or more. Late dilatation to 30 mm or more was rare (16%) in patients who had preoperative cuffs that measured 27 mm or less. The mean late iliac artery size was 16.9 +/- 8.9 mm (range, 10 to 52 mm), and 30% (10 of 33) measured 20 mm or more. CONCLUSIONS: One third of all patients who survive AAA repair experience significant dilatation of their proximal aortic cuff over time. Proximal dilatation is rare but not absent in patients who have smaller initial aortic cuff diameters. This dilatation rarely causes problems after conventional suture fixation, but the long-term implications of cuff dilatation after endoluminal repair are unclear. Our findings suggest that endovascular aortic prostheses that have the ability to continue to self-expand many years after implantation may be required and that endovascular prostheses may not be the best option for patients who have a long life expectancy or for those who have preoperative proximal cuffs greater than 27 mm.

Aorta, Abdominal↗

Primary fibrinolysis during supraceliac aortic clamping.

PURPOSE: An increased incidence of bleeding complications has been observed after supraceliac aortic clamping (SCC). This study was performed to identify possible hemostatic abnormalities that contribute to this problem. METHODS: A prospective cohort study over a 3-month period was performed by comparing hemostatic parameters in 10 consecutive patients who required elective SCC with those of eight concurrent randomly selected control subjects who required infrarenal clamping (IRC) for abdominal aortic reconstruction. Measures of coagulation, fibrinolysis, platelet function, temperature, hemodilution, and hepatic function were performed at selected times before, during, and after operation. RESULTS: Aneurysm size, fibrinogen, D-dimers, prothrombin, partial thromboplastin time, platelet counts, bleeding times, hemodilution, and temperature were comparable in both groups. Patients in the SCC group, however, consistently developed a primary fibrinolytic state within 20 minutes after supraceliac clamping, reflected by significantly decreased euglobulin clot lysis times (ECLT; p < 0.0001), elevated tissue plasminogen activator (t-PA) levels (p < 0.0006), elevated t-PA-to-plasminogen activator inhibitor-1 ratios (p < 0.0001), and reduced alpha 2-antiplasmin levels (p < 0.002). SCC produced hepatocellular injury documented by elevations in both aspartate transaminase (p < 0.0001) and lactate dehydrogenase (p < 0.009). CONCLUSIONS: SCC rapidly induces a primary fibrinolytic state manifested by increased circulating t-PA, reduced alpha 2-antiplasmin, and increased fibrinolytic activator-to-inhibitor ratios. These effects may be a result of hepatic hypoperfusion caused by SCC leading to insufficient clearance of t-PA. Antifibrinolytic agents may be of benefit if bleeding develops after aortic procedures that require supraceliac clamping.

Aged↗

Research and clinical issues in chronic venous disease.

The purpose of this study was to summarize the current issues in chronic venous disease by reviewing of the literature relating to the condition. The review was conducted by members of the Committee on Research of the American Venous Forum and includes the Committee's venous disease and current/future directions. Progress in the understanding and management of chronic venous problems has lagged behind that in arterial disease, despite the large number of patients affected. The complex pathophysiology of venous problems, lack of accepted evaluation standards and lack of prosthetic conduits are some of the factors which contribute to this. New information in these areas has laid the foundation for advances in both operations and non-operative therapy. In conclusion, many opportunities for clinical and basic research in the area of chronic venous disease are available. Application of basic science techniques, including those of molecular biology, will lead to new insights into pathophysiology of chronic venous syndrome. Developments in technology, classification and basic science suggest multiple new potentials therapeutic approaches in the next decade.

Blood Vessel Prosthesis Implantation↗

Posterior exposure for popliteal-crural bypass: a useful approach.

The distal popliteal artery and proximal crural vessels represent common locations for atherosclerotic occlusive disease, especially in the diabetic subpopulation. Symptoms such as pain at rest, distal ulceration, and gangrene are associated with a high risk of limb loss unless arterial flow can be restored. Surgical revascularization is the most appropriate treatment in these patients, using autogenous vein to bypass from the popliteal artery to a crural artery beyond the area of stenosis. The posterior approach is an ideal method with which to achieve this goal. Lesser saphenous vein may be harvested from the same incision used to expose the inflow and outflow vessels. The technique minimizes the length of required conduit and preserves the greater saphenous vein for subsequent use. The wound problems associated with medial vein harvest incisions are less frequent. A through knowledge of the anatomy of the region will allow one to use the posterior approach in selected patients with popliteal and infrapopliteal occlusive disease, providing an additional tool for use in patients with limb-threatening lower extremity ischemia.

Arteriosclerosis↗

Measurement of carotid bifurcation pressure gradients using the Bernoulli principle.

Current randomized prospective studies suggest that the degree of carotid stenosis is a critical element in deciding whether surgical or medical treatment is appropriate. Of potential interest is the actual pressure drop caused by the blockage, but no direct non-invasive means of quantifying the hemodynamic consequences of carotid artery stenoses currently exists. The present prospective study examined whether preoperative pulsed-Doppler duplex ultrasonographic velocity (v) measurements could be used to predict pressure gradients (delta P) caused by carotid artery stenoses, and whether such measurements could be used to predict angiographic percent diameter reduction. Preoperative Doppler velocity and intraoperative direct pressure measurements were obtained, and per cent diameter angiographic stenosis measured in 76 consecutive patients who underwent 77 elective carotid endarterectomies. Using the Bernoulli principle (delta P = 4v(2), pressure gradients across the stenoses were calculated. The predicted delta P, as well as absolute velocities and internal carotid artery/common carotid velocity ratios were compared with the actual delta P measured intraoperatively and with preoperative angiography and oculopneumoplethysmography (OPG) results. An end-diastolic velocity of > or = 1 m/s and an end-diastolic internal carotid artery/common carotid artery velocity ratio of > or = 10 predicted a 50% diameter angiographic stenosis with 100% specificity. Although statistical significance was reached, preoperative pressure gradients derived from the Bernoulli equation could not predict actual individual intraoperative pressure gradients with enough accuracy to allow decision making on an individual basis. Velocity measurements were as specific and more sensitive than OPG results. Delta P as predicted by the Bernoulli equation is not sufficiently accurate at the carotid bifurcation to be useful for clinical decision making on an individual basis. However, end-diastolic velocities alone as well as internal carotid artery/ common carotid artery velocity ratios are highly specific in the prediction of clinically significant carotid stenoses. An end-diastolic velocity of > or = 1 m/s accurately identifies a 50% or greater diameter stenosis, and thus may in some cases be sufficient for operation.

Blood Flow Velocity↗

Activated protein C resistance: prevalence and implications in peripheral vascular disease.

PURPOSE: Activated protein C (APC) is a naturally occurring anticoagulant that interacts with factors V and VIII to inhibit the clotting cascade. Resistance to APC (APC-R), hypothesized to occur as a result of an abnormal factor V, has been documented in up to 40% of patients with venous thrombotic events, but its prevalence in patients with arterial disease remains ill defined. METHODS: With an assay of APC resistance that expresses the ratio of the activated partial thromboplastin time with and without the addition of exogenous APC, APC resistance ratios were quantitated in 200 individuals comprising 177 patients with vascular disease and 23 control subjects. An abnormal activated partial thromboplastin time was present in four patients who were excluded from analysis. The 173 remaining patients formed the study population and were divided into diagnostic subgroups on the basis of the most symptomatic problem. RESULTS: APC resistance was documented in 20 individuals, representing 11.6% of the study group. The highest prevalence of APC resistance was observed in patients with lower extremity occlusive disease, with the APC-R ratio below 2.0 in 13.7%. Within the subgroup of individuals with lower extremity disease, 76 patients (10 with APC-R, 13.2%) underwent infrainguinal bypass and were monitored a mean of 47 +/- 8 months. Occlusion of the arterial reconstruction occurred in 22 patients (29%). Six (60%) of the patients with APC-R had failed reconstructions, versus 16 (24%) of 66 patients without APC-R (p = 0.02). CONCLUSIONS: These findings suggest that APC-R is relatively common in patients with peripheral vascular disease, especially in those with lower extremity occlusive disease. APC-R appears to be a risk factor for failure of infrainguinal bypass. These observations suggest that screening for APC-R may be useful in patients with peripheral vascular disease, providing the opportunity to restore the normal thrombogenic balance with anticoagulant therapy in susceptible individuals.

Aged↗

Thrombolysis or peripheral arterial surgery: phase I results. TOPAS Investigators.

PURPOSE: Thrombolytic therapy is widely used in the treatment of peripheral arterial occlusion, but prospective, randomized comparisons with standard therapy remain few. A multicenter trial of thrombolysis or peripheral arterial surgery (TOPAS) was organized to compare critically the use of recombinant urokinase (rUK) or surgery for the initial treatment of acute lower-extremity ischemia. Phase I of the trial was designed as a dose-ranging trial to evaluate the safety and efficacy of three doses of rUK in comparison with surgery. METHODS: In a multicenter, prospective, double-blind comparison, 213 patients who had acute lower-extremity ischemia for 14 days or fewer were randomized to one of two groups. The first group received one of three dosages of rUK (catheter-directed at 2000, 4000, or 6000 IU/min for 4 hours, then 2000 IU/min to a maximum of 48 hours). The second group underwent surgery. Successful thrombolysis was followed by surgical or endovascular interventions when anatomic lesions responsible for the occlusion were unmasked. Patients were followed-up for 1 year; data were evaluated on an intent-to-treat basis. RESULTS: The 4000 IU/min rUK dosage was chosen as the most appropriate thrombolytic regimen because it maximized lytic efficacy against the risk of bleeding. Complete (> 95%) lysis of thrombus was achieved in 71% of the 49 patients who were randomized to the 4000 IU/min group, with a mean infusion time of 23 hours. In contrast, complete lysis was achieved in 67% of patients who received 2000 IU/min and in 60% of patients who received 6000 IU/min. Hemorrhagic complications occurred in 2% of the 4000 IU/min group versus 13% of the 2000 IU/min group (p = 0.05) and 16% of the 6000 IU/min group (p = 0.03). In a comparison of the 4000 IU/min group with the surgical group, the 1-year mortality rate (14% vs 16%) or amputation-free survival rate (75% vs 65%) did not differ significantly. The frequency and magnitude of surgery in the patients randomized to rUK were decreased (p < 0.001). CONCLUSION: The preliminary results suggest that an initial rUK dose of 4000 IU/min is safe and efficacious in the treatment of acute lower-extremity ischemia. rUK therapy is associated with limb salvage and patient survival rates similar to those achieved with surgery, concurrent with a reduced requirement for complex surgery after thrombolytic intervention.

Acute Disease↗

Thrombolysis with prourokinase versus urokinase: an in vitro comparison.

PURPOSE: Despite advantages demonstrated in vitro, no single thrombolytic agent has been clearly shown to be superior to another in the clinical setting. Prourokinase has recently received attention as a new thrombolytic agent with higher fibrin specificity. The thrombolytic activity of prourokinase, however, remains ill defined. The purpose of this study was to evaluate thrombolysis with prourokinase in comparison to urokinase in vitro. METHODS: We used an in vitro parallel channel perfusion model that simulates catheter-directed thrombolysis in the peripheral arterial system. Radiolabeled thrombi were subjected to 90 minutes of endhole catheter-directed infusion with either prourokinase 5000 IU/ml, urokinase 5000 IU/ml; or 5% dextrose in water at 4 ml/hr. RESULTS: Prourokinase and urokinase were found to be equivalent with respect to thrombolytic effect. Percent lysis was maximal at 90 minutes in both the urokinase and prourokinase groups. Prourokinase and urokinase were found to be equally effective in restoring flow through thrombosed graft segments. CONCLUSION: Prourokinase appears to offer little benefit over urokinase with respect to thrombolytic activity in an in vitro model that closely resembles the clinical setting. If prourokinase is to be accepted as an alternative to urokinase, advantages must relate to differences in fibrin specificity.

Catheterization↗

Thrombolysis or operation for peripheral arterial occlusion.

Patients with peripheral arterial occlusion may be treated with one of three distinct treatment strategies: observation and/or anticoagulation alone, operative intervention, or catheter-directed thrombolytic therapy. The severity of symptoms is the most important clinical parameter with which to formulate clinical strategies. Patients with non-lifestyle limiting claudication may be best managed without arteriographic investigation, managing symptoms conservatively with exercise, cessation of smoking, and occasionally the oral pharmacologic agent pentoxifylline. Patients with threatened limbs in the form of rest pain or tissue loss carry a high risk of limb loss without intervention. These patients should undergo arteriography with consideration of endovascular intervention for focal lesions and bypass grafting for more diffuse disease. Patients with more acute symptoms may be best treated with catheter-directed thrombolytic therapy, addressing unmasked lesions responsible for the occlusion with an operative or endovascular approach. In all cases, the appropriate therapy must be tailored to the clinical presentation, the anatomic distribution of disease, and the experience of the clinical team.

Arterial Occlusive Diseases↗

Differential thrombogenicity of artery and vein: the role of von Willebrand factor.

There exists clinical evidence for a difference in the relative thrombogenicity of arterial and venous surfaces. We studied this phenomenon in an in vitro model where the effects of hemodynamic differences could be controlled. Nonanticoagulated human blood was perfused across injured (air-insufflated) arterial and venous surfaces in a recirculating perfusion system at shear rates of 500 and 1500/sec. Thrombus formation was assessed by measuring radiolabeled platelet (111In) and fibrin (125I) deposition on the surfaces. The role of von Willebrand factor (vWF) in arterial and venous thrombosis was evaluated by blocking its effect with polyclonal anti-vWF antibody (vWF Ab). Raw data were converted to log10 for statistical analysis. The increased thrombogenicity of injured venous vs. arterial segments was confirmed by these studies (p < 0.001). The addition of vWF Ab decreased platelet and fibrin deposition (p < 0.001) and these effects were greater in veins than in arteries. The difference in platelet deposition between arteries and veins was more pronounced at lower shear rates (p < 0.05), an effect not observed with fibrin deposition. To determine whether the increased thrombogenicity of veins could be explained by an increased content of subendothelial vWF, the amount of vWF was assessed by incubating injured vessels with 125I vWF Ab and then measuring the radioactivity of the vessels. Veins had a higher content of vWF than arteries, as implied by the higher amount of radiolabeled vWF Ab (813 +/- 90 in veins vs. 2173 +/- 317 in arteries, p < 0.001). These observations suggest that increased thrombogenicity of veins may in part be explained by intrinsic differences in subendothelial vWF and subsequent platelet attachment.

Animals↗