Biomedical subjects

C K Shortell

Publications and source records attributed to C K Shortell.

33 records · Page 2Linked to original sources

PubMed1994

Plasminogen acceleration of urokinase thrombolysis.

PURPOSE: A relative deficiency of plasminogen within the thrombus may be the rate limiting factor in clot lysis. METHODS: To investigate this hypothesis, we used an in vitro perfusion system and expanded polytetrafluoroethylene graft segments filled with radiolabeled human thrombus. Three groups of five perfusions were compared: (1) urokinase infusion (333 IU/min) into clots laced with buffer, (2) urokinase infusion (333 IU/min) into clots laced with plasminogen (44 CU), and (3) control, D5W infusion into clots laced with buffer. Two end points were measured over time: the amount of lysed thrombus and the flow through the graft. RESULTS: Urokinase infusion resulted in augmented flow through the graft when compared with control (p < 0.05). Lacing with plasminogen resulted in more rapid restoration of flow when compared with urokinase infusion alone (p < 0.05). Similarly, the rate of clot dissolution was significantly greater in plasminogen-laced thrombi (p < 0.05) when compared with the control and urokinase groups. Embolization of particles of thrombus was uniformly observed in the urokinase group, resulting in a temporary decrease in flow through the thrombosed graft. This event characteristically occurred after 60 minutes of infusion but was never seen in the urokinase/plasminogen treatment group. CONCLUSIONS: These results suggest that plasminogen supplementation of urokinase thrombolysis may result in significant clinical benefits with respect to the rate of clot lysis and the uniformity of clot dissolution with a lower likelihood of secondary embolization.

Analysis of Variance↗

PubMed1994

A comparison of thrombolytic therapy with operative revascularization in the initial treatment of acute peripheral arterial ischemia.

PURPOSE: Despite the widespread use of intraarterial thrombolytic therapy for peripheral arterial occlusive disease, a randomized study comparing its efficacy with that of operative intervention has never been performed. This study evaluates the potential of intraarterial urokinase infusion to provide clinical benefits in patients with acute peripheral arterial occlusion. METHODS: Patients with limb-threatening ischemia of less than 7 days' duration were randomly assigned to intraarterial catheter-directed urokinase therapy or operative intervention. Anatomic lesions unmasked by thrombolysis were treated with balloon dilation or operation. The primary end points of the study were limb salvage and survival. RESULTS: A total of 57 patients were randomized to the thrombolytic therapy group, and 57 patients were randomized to the operative therapy group. Thrombolytic therapy resulted in dissolution of the occluding thrombus in 40 (70%) patients. Although the cumulative limb salvage rate was similar in the two treatment groups (82% at 12 months), the cumulative survival rate was significantly improved in patients randomized to the thrombolysis group (84% vs 58% at 12 months, p = 0.01). The mortality differences seemed to be primarily attributable to an increased frequency of in-hospital cardiopulmonary complications in the operative treatment group (49% vs 16%, p = 0.001). The benefits of thrombolysis were achieved without significant differences in the duration of hospitalization (median 11 days) and with only modest increases in hospital cost in the thrombolytic treatment arm (median $15,672 vs $12,253, p = 0.02). CONCLUSIONS: Intraarterial thrombolytic therapy was associated with a reduction in the incidence of in-hospital cardiopulmonary complications and a corresponding increase in patient survival rates. These benefits were achieved without an appreciable increase in the duration of hospitalization and with only modest increases in hospital cost, suggesting that thrombolytic therapy may offer a safe and effective alternative to operation in the initial treatment of patients diagnosed with acute limb-threatening peripheral arterial occlusion.

Acute Disease↗

PubMed1994

Acute peripheral arterial occlusion: predictors of success in catheter-directed thrombolytic therapy.

PURPOSE: To determine predictors of clot dissolution in patients undergoing catheter-directed urokinase thrombolysis for peripheral arterial occlusion (PAO). MATERIALS AND METHODS: The study included 103 patients with limb-threatening symptoms of embolism lasting 14 days or less and resulting from embolism (n = 20) or thrombosis (n = 83). Successful lysis was defined as restitution of antegrade flow with less than 20% diameter reduction by residual thrombus. Stepwise logistic regression was used to analyze the data. RESULTS: Relevant clinical variables were diabetic status (odds ratio, 0.75; P = .04 for diabetic patients), conduit type (1.25; P = .04 for native artery and 1.51; P = .02 for prosthetic graft), and number of arterial segments involved (1.60; P = .02 for one level and 1.42; P = .03 for two levels). Important procedural variables included intrathrombus positioning of catheter ports (odds ratio, 7.40; P = .001) and guide wire passage through the occlusion (3.10; P = .003). Absolute thrombus volume was nonpredictive but correlated with reperfusion time (P = .02) and infusion time (P = .01). CONCLUSION: Predictive parameters may help in the selection of candidates with PAO for thrombolytic therapy.

Acute Disease↗

PubMed1993

Intraoperative autotransfusion in aortic surgery.

PURPOSE: Intraoperative autotransfusion is frequently used in aortic surgery, despite the paucity of data regarding its safety and efficacy. This study was designed to compare whole blood autotransfusion with homologous transfusion for the replacement of blood lost during abdominal aortic procedures. METHODS: Whole blood autotransfusion was evaluated in 200 patients undergoing aortic reconstructive procedures during a 3-year period. Collection and reinfusion of unwashed filtered shed blood was undertaken in 100 patients, and clinical, laboratory, and economic parameters were compared with those in a group of 100 patients undergoing aortic operation with homologous banked blood replacement. RESULTS: The two groups were comparable with respect to demography, the type of procedure, baseline laboratory profile, and the frequency of coexistent medical illnesses. The amount of blood salvaged and reinfused averaged 1729 +/- 68 ml in the autotransfusion group. Patients undergoing autotransfusion received a mean of 0.6 +/- 0.1 units of banked blood during operation, compared with 3.4 +/- 0.1 units in the homologous group (p < 0.001). Operative morbidity and mortality rates were comparable between the groups, as were length of hospital stay and total hospital costs. Coagulopathy, renal insufficiency, abnormalities of oxygen exchange, and electrolyte disorders were infrequent. Autotransfusion offered significant advantages over homologous blood replacement with respect to improved preservation of circulating platelets (201 +/- 9 vs 157 +/- 6 x 10(3)mm3, p < 0.001) and coagulation factors (242 +/- 11 vs 196 +/- 14 mg fibrinogen/dl, p < 0.01) and limitation of exposure to homologous blood (34% vs 92%, p < 0.001). There was a significant cost advantage with the use of autotransfusion, with an average savings of $288 in hospital expenses associated with blood products and infusion equipment. Patients undergoing autotransfusion demonstrated aberrations in fibrin degradation products (33 +/- 4.4 vs 9.6 +/- 3.2 micrograms/ml, p < 0.001) and free plasma hemoglobin (29 +/- 9.1 vs 9.4 +/- 0.5 mg/dl, p < 0.05), but these laboratory abnormalities did not acquire clinical significance. CONCLUSION: These data suggest that autotransfusion of unwashed, filtered blood is a safe and efficacious alternative to homologous blood replacement in patients undergoing major aortic reconstructive procedures.

Aged↗

PubMed1992

An animal model of fibrinolytic bleeding based on the rebleed phenomenon: application to a study of vulnerability of hemostatic plugs of different age.

The primary bleeding time is prolonged when tested during the infusion of both plasminogen activators and anticoagulants, and such sites frequently exhibit rebleeding after initial hemostatic control. This study describes an animal (rabbit) model which distinguishes fibrinolytic from anticoagulant hemorrhage and further applies the model to the study of hemostatic plugs of increasing age. In this model, rebleeding occurred from hemostatically-stable ear puncture sites induced prior to infusion of streptokinase (SK) or recombinant tissue-plasminogen activator (rt-PA), but not of heparin or hirudin. This distinction was apparent even for lesions induced only 15 minutes prior to the infusion and fibrinolytic bleeding was observed in such lesions induced up to 24 hours earlier. Post-infusion sites bled more quickly than did pre-infusion sites, and there was a gradual decrease in susceptibility of such prior trauma sites for rebleeding, evidenced not only by a lower proportion of sites that rebled, but also by a longer lag time after starting SK or rt-PA before such rebleeding occurred. At the dosages tested, SK showed a trend (not statistically significant) toward more sites that rebled, while rt-PA showed a trend towards a longer duration of rebleeding. Thus, this animal model of rebleeding appears to be unique for fibrinolytic agents and allows for more detailed study of the physiological mechanisms of such bleeding and for a multifaceted comparison of the bleeding potential of plasminogen activators.

Animals↗

PubMed1992

Peroneal artery bypass: a multifactorial analysis.

Sixty-two bypass grafts to the peroneal artery were performed at the University of Rochester Medical Center between 1984 and 1990. An autogenous conduit was used in 45 patients and a prosthetic conduit in 17 patients. Primary cumulative patency rates were 49% at two years and 30% at four years following operation. Limb salvage was achieved in 68% of patients. The two year cumulative patency rate was significantly better when the peroneal artery was of good quality arteriographically compared with those in which stenoses were present (75% versus 25%, p less than 0.05); in patients without inflow disease compared with patients with inflow disease (56% versus 11%, p less than 0.05); and in saphenous vein grafts compared with prosthetic grafts (55% versus 17%, p less than 0.05). The factors that did not influence patency were the presence of a direct peroneal collateral vessel filling a pedal vessel, age, sex, diabetes, and the size of the peroneal artery. The results of peroneal artery bypass in end-stage patients are dependent on the presence of adequate autogenous vein and a recipient peroneal vessel free of disease. Under these circumstances, the results of the procedure approach that of standard femorotibial reconstruction.

Aged↗

PubMed1992

An evaluation of new methods of expressing aortic aneurysm size: relationship to rupture.

The diameter of aortic aneurysms were standardized to measures of patient size and normal aortic size in an effort to define indexes that might be more predictive of aneurysm rupture than raw aneurysm diameter alone. Normal aortic diameters were measured in 100 patients undergoing abdominal CT scans for other reasons, and an average infrarenal aortic diameter of 2.10 +/- 0.05 cm was observed. Normal aortic diameter was dependent on both age and sex, ranging from 1.71 +/- 0.06 cm in women below age 40 years to 2.85 +/- 0.04 cm in men above age 70 years. Overall, 11 (5.1%) of the ruptures occurred in aneurysms less than 5 cm in diameter, and four (1.9%) occurred in aneurysms less than 4.0 cm in diameter. When the CT scans of 100 patients undergoing elective aneurysm resection were compared with those of 36 patients with ruptured aneurysms, no threshold diameter value accurately discriminated between the two groups. However, standardization of the aneurysm diameter to the transverse diameter of the third lumbar vertebral body as an index of patient body size produced an accurate predictor of rupture when a threshold ratio of 1.0 was used. No aneurysm ruptured below this ratio, but 29% of elective aneurysms were smaller than the vertebral body diameter. Receiver operating characteristic curve analysis confirmed the superiority of the aneurysm to vertebral body diameter ratio as a discriminator of ruptured aneurysms. It appears that aneurysm diameter alone is not sufficiently predictive of rupture to be used as the sole indication for elective resection.

Adult↗

PubMed1992

Vascular disease in the antiphospholipid syndrome: a comparison with the patient population with atherosclerosis.

The antiphospholipid syndrome was diagnosed in 19 of 1078 patients treated between 1987 and 1991. All patients with antiphospholipid syndrome had either anticardiolipin antibody (16/19) or lupus anticoagulant (10/19); three patients had thrombocytopenia, eight patients had a prolonged partial thromboplastin time, and 10 patients had an elevated erythrocyte sedimentation rate. The most common site of involvement was the cerebral circulation (nine patients), manifested by transient ischemic attacks or stroke. Eight patients had upper extremity disease, characterized by symptoms of Raynaud's phenomenon, with angiographic lesions involving the brachial, radial, ulnar, and/or digital arteries. Lower extremity disease occurred in seven patients, with clinical presentations similar to those of atherosclerosis and varying angiographic patterns. In comparison with the population having atherosclerosis, patients with arterial manifestations of antiphospholipid syndrome were more likely to be women (13 of 19 versus 411 of 1078, p less than 0.02), were significantly younger (46.2 years versus 63.6 years, p less than 0.0001), did not smoke (1 of 19 patients versus 700 of 1078, p less than 0.0001), had a higher percentage of upper extremity involvement (8 of 18 versus 13 of 1078, p less than 0.0001), and had a higher incidence of early graft failure (9 of 12 grafts versus 13 of 371 grafts, p less than 0.0001). The syndrome is associated with the repetitive failure of vascular reconstructions and occlusion of native vessels. Antiphospholipid syndrome should therefore be suspected in young, female, nonsmokers with vascular disease, especially those with involvement of the upper extremity, cerebrovascular disease with normal findings on extracranial carotid angiography, and premature graft failure.

Adult↗

PubMed1992

Future alternatives to heparin: low-molecular-weight heparin and hirudin.

The antithrombotic effects of standard heparin were compared with those of low-molecular-weight heparin (LMWH) and hirudin by use of an in vitro perfusion system. Fresh blood collected from human volunteers was treated with varying doses of these three agents and perfused in a recirculating system over everted porcine vein segments. A low shear rate (100/sec) was selected to simulate conditions in large arteries and veins. Platelet and fibrinogen deposition were evaluated with indium 111 and iodine 125 radiolabels, respectively. Anticoagulant activity was assessed by measuring the activated clotting time (ACT). Anti-Xa activity was assayed to determine the degree to which these agents used antithrombin III pathways. Low-molecular-weight heparin was the weakest anticoagulant, requiring 32 micrograms/ml blood to double the ACT. By contrast, the ACT doubled with only 0.75 and 1.10 micrograms/ml blood of heparin and hirudin, respectively. Heparin and hirudin inhibited platelet and fibrin deposition at equivalent doses. Low-molecular-weight heparin was a less potent inhibitor of fibrin than heparin or hirudin. Hirudin, a direct thrombin inhibitor, exhibited minimal anti-Xa activity, contrasted with 0.14 anti-Xa units/micrograms for LMWH and 0.13 anti-Xa units/mg for heparin. These data suggest that heparin and hirudin are more potent anticoagulants and antiplatelet agents than LMWH.

Analysis of Variance↗

PubMed1991

Low dose heparin therapy: in vitro verification of antithrombotic effect.

Low dose heparin therapy has been used routinely for prophylaxis of deep venous thrombosis, yet in vitro data regarding its antithrombotic effects are sparse. The effects of heparin on venous thrombus formation were studied in an in vitro perfusion system. Fresh blood collected from human volunteers was treated with varying heparin doses and perfused at a shear rate of 100 sec-1 over everted, injured porcine vein segments, simulating conditions in the venous circulation. Platelet and fibrin deposition were measured by use of indium 111 and iodine 125 radiolabels, respectively. The effects of heparin on the intrinsic coagulation cascade were monitored by the activated clotting time. Increasing doses of heparin resulted in significant reductions in fibrin and platelet deposition (ANOVA F = 2.67 and 3.17, respectively, p less than 0.05). At a dose of only 0.19 USP units/ml blood, equivalent to a 1000 unit bolus of heparin in a 70 kg man, a noticeable reduction in both fibrin and platelet deposition was observed without an increase in the activated clotting time. These data confirm the antithrombotic effects of heparin at low dose ranges and may explain the clinically observed phenomenon of deep venous prophylaxis without an appreciable alteration in the conventional coagulation assays.

Animals↗

PubMed1991

The hemodynamics of thrombus formation in arteries.

Alterations in arterial blood flow are thought to predispose to thrombus formation, but the exact relationships have not been fully elucidated. The effect of varying blood flows on the accumulation of thrombotic material within arteries was investigated, with use of shear rate as an index of flow across the luminal surface. Partially denuded rabbit aortas were perfused with fresh nonanticoagulated human blood for 3 minutes, with an in vitro recirculating apparatus, Indium 111-labeled platelets, and fibrinogen I 125. Shear rates ranged from zero to 1500 sec-1, correlating with the hemodynamics of various segments of the human arterial tree. A significant correlation was observed between shear rate and platelet deposition, ranging from 5.2 +/- 2.8 x 10(6) platelets/cm2 of vessel surface area at zero shear to a maximum of 64.7 +/- 8.3 x 10(6) platelets/cm2 at a shear rate of 1500 sec-1 (F = 5.01, p less than 0.05). Fibrin deposition paralleled that of platelets, ranging from 28.2 +/- 7.6 micrograms/cm2 at zero shear to 354.1 +/- 62.7 micrograms/cm2 at a shear rate of 1500 sec-1 (F = 5.91, p less than 0.05). These results suggest that shear rate is a most important determinant of platelet and fibrin deposition on altered arterial surfaces.

Animals↗

PubMed1991

Popliteal artery aneurysms: a 25-year surgical experience.

Operative repair was undertaken for 51 popliteal aneurysms in 39 patients between 1958 and 1990. Operation was performed on an emergency basis in 19 extremities with limb-threatening ischemia and as an elective procedure in 32 extremities. Cumulative limb salvage (94%) rates and patency rates (67%) became significantly different at 6 years (p less than 0.05). Graft patency was affected by clinical presentation and runoff. After 1 year, cumulative patency for extremities with limb-threatening ischemia was significantly lower than for those having an elective operation (69% vs 100%, p less than 0.05). Runoff did not influence graft patency until 3 years, at which time cumulative patency was better in extremities with good runoff than in extremities with poor runoff (89% vs 30%, p less than 0.05). Limb salvage was affected only by presentation. All limb loss (three patients) occurred within the first month in extremities with graft occlusion after operation for limb-threatening ischemia. Runoff did not influence patency rates for extremities with limb-threatening ischemia, since no difference was observed in runoff between the two groups. We conclude that elective repair is indicated in all patients with popliteal aneurysms. It is associated with little risk to the patient, and prevents the need for operation in the setting of limb-threatening ischemia with its poorer overall results and definite incidence of amputation.

Aged↗

PubMed1991

Hepatic adenoma and focal nodular hyperplasia.

Hepatic adenoma and focal nodular hyperplasia are benign lesions of the liver. The incidence of these conditions has been increasing since 1970. Hepatic adenoma primarily affects young women of childbearing age who have a long history of using oral contraceptives, while focal nodular hyperplasia has a wider age distribution and is not associated with the use of oral contraceptives. The most extensive complication of hepatic adenoma is intratumoral or intraperitoneal hemorrhage, which occurs in 50 to 60 per cent of patients. Patients with focal nodular hyperplasia are usually asymptomatic and rarely experience complications. Hepatic adenoma is distinct from focal nodular hyperplasia both in its clinical behavior and its pathologic features; the two can usually be differentiated radiographically using a combination of radionuclide scanning and angiography. There is a proved association between the use of oral contraceptives and the development of hepatic adenoma; the longer the duration of oral contraceptive use, the more the risk of having hepatic adenoma develop. In addition, users of oral contraceptives who have hepatic adenoma develop are likely to have larger tumors and higher rates of bleeding and rupture than nonusers who have hepatic adenoma develop. Although hepatic adenomas may regress after discontinuation of oral contraceptive use, this is not a consistent finding. In addition, it has now been demonstrated that hepatic adenomas do undergo malignant transformation and that this can be detected by measuring the alpha-fetoprotein level. Focal nodular hyperplasia may be a precursor for fibrolamellar hepatocellular carcinoma. Elective resection of hepatic adenoma has a mortality rate of less than 1 per cent, while the mortality rate with free rupture is 5 to 10 per cent. Because of the relative safety of elective versus emergency resection and the potential for malignant change, the treatment of choice for hepatic adenoma is surgical resection.

Adenocarcinoma↗

PubMed1991

Carcinoma of the parathyroid gland: a 30-year experience.

Eleven patients with parathyroid carcinoma and 186 patients with parathyroid adenoma were seen between 1958 and 1990. Significant differences (p less than 0.01) were found between the two groups in calcium and parathormone levels, lesion size, presence of palpable mass, and severity of clinical presentation. Initial operative management consisted of parathyroidectomy alone in three patients, all of whom experienced recurrence of disease. Of the eight patients who underwent aggressive surgical management (parathyroidectomy and resection of thyroid or thymus), only one experienced recurrence. Three of the four patients with recurrence underwent multiple thoracic and cervical procedures for control of disease; one patient was treated with medical therapy alone. The mean survival in the surgical group was 17 years; the patient treated with medical therapy survived 10 years. In all four patients, however, treatment was palliative rather than curative. We conclude that patients with primary hyperparathyroidism characterized by markedly elevated serum calcium and parathormone, palpable mass, and severe clinical presentation should be suspected of harboring a parathyroid carcinoma. An aggressive initial surgical approach was considered in these patients. This experience emphasizes the importance of aggressive surgical extirpation in reducing disease recurrence and also for palliation and prolongation of life when recurrence does occur.

Adenoma↗

PubMedDate not supplied

Clinical review: irradiation for lower extremity arterial occlusive disease.

Lower extremity atherosclerosis, a disease of aging, is both widespread and increasing in prevalence-it is estimated that almost 100,000 patients per year in the United States require operative bypass for lower extremity ischemia. It is an axiom of vascular surgery that essentially every bypass graft will eventually fail. Many if not most such failures are due to the process of intimal hyperplasia at one or both anastomoses. The search for a "cure" for intimal hyperplasia has been long, but thus far unrewarding. Recent advances in therapeutic irradiation, however, offer a potential solution to this problem. This review is designed to acquaint the radiation oncologist with the basic concepts behind lower extremity atherosclerosis and its treatment, and to introduce briefly the special problems inherent in considering irradiation of an end-to-side anastomosis.

Anastomosis, Surgical↗