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Biomedical subjects

W C Krupski

Publications and source records attributed to W C Krupski.

At least 19 recordsLinked to original sources

Thrombophilia and activated protein C resistance.

In addition to classic vascular insults such as inflammation, trauma, malignancy, and surgery, a number of hereditary coagulation defects predispose patients to a wide array of thrombotic complications. A novel genetic defect in factor V allowing for resistance to its cleavage by activated protein C has recently been implicated in a significant number of cases of familial thrombophilia. A brief case report and review of the literature is presented to familiarize surgeons to this important and quite frequent cause of hypercoagulability.

Activated Protein C Resistance

Contemporary management of isolated iliac aneurysms.

OBJECTIVE: Because isolated common iliac artery aneurysms are infrequent, are difficult to detect and treat, and have traditionally been associated with high operative mortality rates in reported series, we analyzed the outcomes of operative repair of 31 isolated common iliac artery aneurysms in 21 patients to ascertain morbidity and mortality rates with contemporary techniques of repair. METHODS: A retrospective review study was conducted in a university teaching hospital and a Department of Veterans Affairs Medical Center. Perioperative mortality and operative morbidity rates were examined in 17 men and four women with isolated common iliac artery aneurysms between 1984 and 1997. Ages ranged from 38 to 87 years (mean 69 +/- 8 years). Slightly more than half of the cases were symptomatic, with abdominal pain, neurologic, claudicative, genitourinary, or hemodynamic symptoms. One aneurysm had ruptured and one was infected. There was one iliac artery-iliac vein fistula. All aneurysms involved the common iliac artery. Coexistent unilateral or bilateral external iliac aneurysms were present in four patients; there were three accompanying internal iliac aneurysms. Overall, 52% of patients had unilateral aneurysms and 48% had bilateral aneurysms. Aneurysms ranged in maximal diameter from 2.5 to 12 cm (mean 5.6 +/- 2 cm). No patients were unavailable for follow-up, which averaged 5.5 years. RESULTS: Nineteen patients underwent direct operative repair of isolated iliac aneurysms. One patient had placement of an endoluminal covered stent graft; another patient at high risk had percutaneous placement of coils within the aneurysm to occlude it in conjunction with a femorofemoral bypass graft. Patients with bilateral aneurysms underwent aortoiliac or aortofemoral interposition grafts, whereas unilateral aneurysms were managed with local interposition grafts. There were no deaths in the perioperative period. Only one elective operation (5%) resulted in a significant complication, compartment syndrome requiring fasciotomy. The patient treated with the covered stent required femorofemoral bypass when the stent occluded 1 week after the operation. The patient treated with coil occlusion of a large common iliac aneurysm died 2 years later when the aneurysm ruptured. CONCLUSIONS: Isolated iliac artery aneurysms can be managed with much lower mortality and morbidity rates than aneurysm previously been reported by using a systematic operative approach. Percutaneous techniques may be less durable and effective than direct surgical repair.

Adult

Cocaine-induced peripheral vascular occlusive disease--a case report.

Two patients with cocaine-induced peripheral vascular occlusive disease are presented. A 37-year-old man was admitted to the hospital for evaluation of severe pain and numbness of his feet. He had used cocaine prior to admission. Arteriography showed bilateral occlusions of superficial femoral, popliteal, and trifucation arteries. Despite repeated infusions of urokinase, he developed progressive bilateral gangrene of both legs necessitating bilateral below-knee amputations. The second patient developed similar symptoms after smoking cocaine. Arteriography showed vasospasm bilaterally from the iliac arteries distally. I.v. nitroglycerin infusion caused resolution of the vasospasm and ischemic symptoms.

Acute Disease

Prevalence and associations of abdominal aortic aneurysm detected through screening. Aneurysm Detection and Management (ADAM) Veterans Affairs Cooperative Study Group.

BACKGROUND: Independent risk factors for abdominal aortic aneurysm (AAA) have not been clearly defined in multivariable analyses of large patient populations. OBJECTIVE: To identify factors that are independently associated with AAA and to determine the prevalence of previously unrecognized AAA in defined demographic and risk groups. DESIGN: Cross-sectional screening study. SETTING: 15 Department of Veterans Affairs medical centers. PARTICIPANTS: 73451 veterans who were 50 to 79 years of age and had no history of AAA. MEASUREMENTS: The results of ultrasonographic screening for AAA and a prescreening questionnaire were analyzed using multiple logistic regression. RESULTS: An AAA of 4.0 cm or larger was detected in 1031 participants (1.4%). Smoking was the risk factor most strongly associated with AAA; the odds ratio (OR) for AAAs of 4.0 cm or larger compared with normal aortas (infrarenal aortic diameter < 3.0 cm) was 5.57 (95% CI, 4.24 to 7.31). The association between smoking and AAA increased significantly with the number of years of smoking and decreased significantly with the number of years after quitting smoking. The excess prevalence associated with smoking accounted for 78% of all AAAs that were 4.0 cm or larger in the study sample. Female sex (OR, 0.22 [CI, 0.07 to 0.68]), black race (OR, 0.49 [CI, 0.35 to 0.69]), and presence of diabetes (OR, 0.54 [CI, 0.44 to 0.65]) were negatively associated with AAA. A family history of AAA was positively associated with AAA (OR, 1.95 [CI, 1.56 to 2.43]) but was reported by only 5.1% of participants. Other independently associated factors included age, height, coronary artery disease, any atherosclerosis, high cholesterol levels, and hypertension. CONCLUSIONS: Abdominal aortic aneurysm is associated with multiple factors. Smoking was the risk factor most strongly associated with AAA and may be responsible for most clinically important cases of previously undiagnosed AAA.

Aged

Unusual causes of mesenteric ischemia.

Although complications of generalized atherosclerosis most commonly cause intestinal ischemia, a number of unusual causes may be responsible. These unusual causes can be grouped into six major categories: (1) mechanical, (2) drugs, (3) hematologic, (4) endocrine, (5) vasculopathies, and (6) miscellaneous. Morbidity and mortality rates remain high because these rare diseases frequently go unrecognized until patients suffer adverse outcomes. A high index of suspicion may decrease the delay in diagnosis of mesenteric ischemia caused by these disorders.

Antibodies, Anticardiolipin

Relationship of age, gender, race, and body size to infrarenal aortic diameter. The Aneurysm Detection and Management (ADAM) Veterans Affairs Cooperative Study Investigators.

PURPOSE: To assess the effects of age, gender, race, and body size on infrarenal aortic diameter (IAD) and to determine expected values for IAD on the basis of these factors. METHODS: Veterans aged 50 to 79 years at 15 Department of Veterans Affairs medical centers were invited to undergo ultrasound measurement of IAD and complete a pre-screening questionnaire. We report here on 69,905 subjects who had no previous history of abdominal aortic aneurysm (AAA) and no ultrasound evidence of AAA (defined as IAD > or = 3.0 cm). RESULTS: Although age, gender, black race, height, weight, body mass index, and body surface area were associated with IAD by multivariate linear regression (all p < 0.001), the effects were small. Female sex was associated with a 0.14 cm reduction in IAD and black race with a 0.01 cm increase in IAD. A 0.1 cm change in IAD was associated with large changes in the independent variables: 29 years in age, 19 cm or 40 cm in height, 35 kg in weight, 11 kg/m2 in body mass index, and 0.35 m2 in body surface area. Nearly all height-weight groups were within 0.1 cm of the gender means, and the unadjusted gender means differed by only 0.23 cm. The variation among medical centers had more influence on IAD than did the combination of age, gender, race, and body size. CONCLUSIONS: Age, gender, race, and body size have statistically significant but small effects on IAD. Use of these parameters to define AAA may not offer sufficient advantage over simpler definitions (such as an IAD > or = 3.0 cm) to be warranted.

Aged

Hospital vs home-based exercise rehabilitation for patients with peripheral arterial occlusive disease.

Supervised, hospital-based exercise rehabilitation programs are effective for improving functional status for patients with claudication due to peripheral arterial occlusive disease. However, it has been suggested that unsupervised, home-based exercise programs, which have been relatively little evaluated, would be equally efficacious as compared with hospital-based programs. The authors tested the hypothesis that a hospital-based exercise rehabilitation program would improve treadmill exercise performance more than a home-based program. Of 20 consecutively enrolled patients with claudication, 10 were randomly placed into a supervised, hospital-based program and 10 into an unsupervised, home-based program for a three-month period. Exercise performance was evaluated by treadmill testing using a graded protocol. In addition, functional status was evaluated by the Walking Impairment Questionnaire (WIQ) and the Medical Outcomes Study SF-20 questionnaire (MOS). Patients in the hospital-based program were treated with treadmill walking three times a week for one hour/visit. Patients in the home-based program were instructed to walk at least three times a week and were contacted weekly to provide encouragement and to record compliance with the program. Patients in the hospital-based group improved peak walking time by 137%, pain-free walking time by 150%, and peak oxygen consumption by 19% (all P < 0.05). Patients reported an improved walking distance and speed according to WIQ data (both P < 0.05). In addition, the MOS physical functioning score in the hospital-based group improved by 20 percentage points (P < 0.05). In contrast, patients in the home-based program did not improve exercise performance measured on the treadmill. Improvement in the ability to walk on the treadmill was greater in the hospital-based than the home-based program (P < 0.05). The ability to walk distances was the only questionnaire measure that improved in persons who received the home-based program (P < 0.05). Preliminary results suggest that a supervised, hospital-based program is more effective for improving treadmill exercise performance than an unsupervised, home-based program.

Ambulatory Care

Preoperative cardiac risk management.

CAD is present in most patients with peripheral arterial disease and is the leading cause of morbidity and mortality after vascular operations. Clinical risk assessment attempts to identify those patients at low, intermediate, or high cardiac risk for adverse cardiac outcomes. Additional tests add little information to the estimates obtained by clinical scoring in patients at low risk. Patients with high cardiac risk scores are clearly at increased risk of experiencing postoperative complications, but further investigations are needed only if knowledge of the functional severity or degree of myocardial ischemia will alter subsequent management. In general, high-risk patients should proceed to coronary angiography, intensive perioperative monitoring, alteration in the planned operation, or avoidance of surgery altogether if indications are less than compelling. Those patients identified as intermediate risk by clinical scoring benefit most from additional tests. In these patients special studies or even coronary arteriography may be useful if the vascular surgery can be delayed until myocardial revascularization is completed. Practically, preoperative cardiac work-up must also consider the indication for surgery. Patients who have threatened limbs or ruptured aneurysms or are severely symptomatic cannot afford the time involved for obtaining additional tests. Moreover, the question of what to do with the information provided by special studies is problematic in these patients. For example, if significant symptomatic or asymptomatic CAD is present in a patient with a gangrenous foot, what is gained by the delay in lower extremity revascularization required when prophylactic CABG is performed? Reports supporting prophylactic CAD intervention are nonrandomized and uncontrolled. CABG and PTCA should be performed only on the merits of the patient's cardiac symptoms and coronary artery anatomy, not to enhance safety of the proposed vascular procedure, because advances in surgical and anesthetic techniques and intraoperative and postoperative monitoring have resulted in lower morbidity and mortality of elective vascular surgery.

Arterial Occlusive Diseases

Arterial dissections associated with pregnancy.

Two cases of spontaneous arterial dissection occurring in young, multiparous women shortly after delivery of uncomplicated pregnancies are described. Histologic analysis of arterial tissue samples obtained in both cases at points near and remote from the dissection sites shows evidence of significant arterial degeneration and loss of integrity, with changes similar to those observed in pregnant women, women using oral contraceptives, and animals given female sex hormones. The types of arterial lesions associated with pregnancy and their sites of predilection and the etiologic roles of the hemodynamic stresses of pregnancy and hormones are discussed.

Adult

Carotid artery disease in women.

Our understanding of cerebrovascular disease in women is hampered by a paucity of studies that include adequate numbers of female patients. Most studies are heavily biased toward men. Although women have fewer strokes than men and have a better long-term prognosis after strokes or TIAs, cerebrovascular disease still affects large numbers of women. Presently, there is little convincing evidence that standard medical therapy with aspirin for prevention of strokes in women is of benefit. Perhaps, inclusion of insufficient numbers of women in the aspirin trials for symptomatic carotid stenoses explains the apparent lack of therapeutic efficacy. Although ticlopidine does not appear particularly promising for prevention of stroke, other novel antiplatelet and antithrombotic agents are being developed and need to be tested in women. Carotid endarterectomy prevents strokes in women and men, but women enjoy a lesser benefit; this appears to be true both for symptomatic and asymptomatic carotid stenoses. Whereas restenosis is more common in women than men, most lesions remain asymptomatic. Surgery will probably remain the mainstay of treatment for cerebrovascular disease in women and men, but in this era of "gender correctness," the striking absence of reliable data exclusively applicable to women confirms the need for additional studies.

Carotid Artery Diseases

Lasting safe interruption of endarterectomy thrombosis by transiently infused antithrombin peptide D-Phe-Pro-ArgCH2Cl in baboons.

To evaluate the relative antithrombotic efficacy and hemostatic safety of antithrombin therapy for vascular thrombus formation at sites of mechanical vascular injury, we administered the potent and specific irreversible synthetic antithrombin D-PHE-PRO-ARG chloromethyl ketone (D-FPRCH2Cl) after performing carotid endarterectomies in baboons. The continuous intravenous infusion of D-FPRCH2Cl, 100 nmol/kg per minute for 1 hour, abolished acute carotid endarterectomy thrombosis for at least 48 hours. The plasma level of D-FPRCH2Cl during the infusion was maintained steady at 7.2 +/- 0.9 mumol/L, but decreased rapidly after discontinuing its infusion (T50 17 minutes). Platelet deposition, measured in real time using autologous 111In-platelet scintillation camera imaging, was 1.51 +/- 0.40 x 10(8) platelet/cm in the 14 treated animals 90 minutes postoperatively, compared with 11.7 +/- 1.16 x 10(8) platelet/cm in 14 heparin-treated controls (P < .002). The antithrombotic benefit was equivalent for treatment begun either 5 minutes before (nine animals) or 15 minutes after (five animals) reestablishing flow in the operated vessel, ie, 1.59 +/- 0.36 x 10(8) platelet/cm versus 1.35 +/- 0.51 x 10(8) platelet/min, respectively; P > .5. Endarterectomy thrombosis remained decreased for at least 48 hours postoperatively, as determined by the ratio between net 111In-platelet radioactivity at the endarterectomized site versus whole blood (ratio 0.82 +/- 0.25 in the treatment group v 3.03 +/- 0.51 in heparin controls at 90 minutes, P < .005; and 0.85 +/- 0.23 v 3.25 +/- 0.48 at 48 hours, P < .002). The marked reduction in endarterectomy thrombosis in treated animals at 48 hours was confirmed by scanning electron microscopy. Thrombin activity formed rapidly and became immediately bound to thrombus on thrombogenic segments in untreated control studies; treatment with D-FPRCH2Cl irreversibly inactivated the thrombus-bound thrombin. Hemostatic function, as measured by bleeding time (BT), activated partial thromboplastin time (APTT), and prothrombin time (PT) was impaired throughout the intravenous administration of D-FPRCH2Cl (BT > 30 minutes, APTT > 150 seconds, PT > 50 seconds); BT, APTT, and PT values were normal 30 minutes after discontinuing the infusions. As expected, blood loss into the surgical wound was substantial in nine animals receiving therapy initiated before restoring flow in the operated vessel (mean 95 mL, range 45 to 130 mL). By contrast, beginning D-FPRCH2Cl therapy in five animals 15 minutes after restoring arterial flow, a time when surgical hemostasis had been achieved, prevented excessive blood loss (mean 15 mL, range 10 to 35 mL; P < .01 compared with earlier treatment) without compromising the antithrombotic effects.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Chloromethyl Ketones

Interruption of vascular thrombosis by bolus anti-platelet glycoprotein IIb/IIIa monoclonal antibodies in baboons.

PURPOSE: Because the platelet membrane receptor glycoprotein IIb/IIIa plays a central role in the recruitment of platelets into forming thrombus, therapeutic inhibition of this receptor complex may be particularly useful to prevent thrombosis after small vessel arterial manipulation. METHODS: The relative hemostatic safety and antithrombotic efficacy for thrombus formation at sites of endarterectomy and implanted prosthetic vascular graft of a murine monoclonal antibody (LJ-CP8) against platelet glycoprotein IIb/IIIa have been determined in baboons after bolus injections in doses (10 mg/kg) that block platelet receptor function for fibrinogen and other adhesive glycoproteins (absent platelet aggregation and bleeding times > 30 minutes without affecting circulating platelet counts). RESULTS: Thrombus formation was eliminated by LJ-CP8 at sites of surgical endarterectomy in fresh segments of homologous aorta incorporated into chronic exteriorized arteriovenous femoral shunts (accumulation of indium 111-labeled platelets fell from 4.40 +/- 0.89 x 10(9) platelets/cm in control animals [n = 6] to 0.23 +/- 0.01 x 10(9) platelets/cm in treated animals [n = 4]; p < 0.005). The formation of thrombus was also abolished by LJ-CP8 at sites of 1 cm prosthetic vascular grafts (4 mm inner diameter polytetrafluoroethylene grafts) interposed into common carotid arteries (deposition of indium 111-labeled platelets decreased from 2.57 +/- 0.43 x 10(9) platelets/cm [n = 5] to 0.16 +/- 0.06 x 10(9) platelets/cm, [n = 4]; p = 0.004). However, LJ-CP8 injections produced substantial bleeding in the surgical wound during the first few hours after operation. Thirty days after operation all four graft implants were patent in JJ-CP8-treated animals compared with two of five in control animals (p = 0.06). CONCLUSIONS: We conclude that profound inhibition of platelet glycoprotein IIb/IIIa receptor function by single bolus injection of LJ-CP8 monoclonal antibody transiently abolishes platelet hemostatic function, eliminates acute thrombus formation at sites of endarterectomy and prosthetic vascular graft implants, and may improve vascular patency.

Animals

Exteriorized chronic aorto-caval arteriovenous access shunts in the baboon (Papio cynocephalus).

A chronic arteriovenous (AV) blood access shunt has been developed in baboons. It is composed of silicone rubber tubing extensions bonded to vascular graft polytetrafluoroethylene (ePTFE) cuffs, for creating anastomoses with the distal aorta and inferior vena cava. Following surgical implantation, shunts remain patent for months (X = 9 +/- 2.5 months) and provides long-term ex vivo access to non-anticoagulated blood (Mean Blood Flow = 312 +/- 69 mL/min).

Animals

Primary aortoduodenal fistula caused by severe atherosclerosis, not by aneurysm.

Primary aortoduodenal fistula is an uncommon cause of massive upper gastrointestinal hemorrhage usually due to pressure erosion of an abdominal aortic aneurysm into the third portion of the duodenum. This report describes a case of a 59-year-old man who died of massive gastrointestinal hemorrhage due to a primary aortoduodenal fistula. This case is unique in that the fistula formed as a result of complex atherosclerotic disease of the abdominal aorta, with adventitial chronic inflammation and foreign body reaction against atheromatous plaque, and not from an aneurysm. We were unable to identify any other reports of aortoduodenal fistulas developing spontaneously in the absence of aneurysmal disease of the aorta.

Aorta, Abdominal

Comparison of cardiac morbidity rates between aortic and infrainguinal operations: two-year follow-up. Study of Perioperative Ischemia Research Group.

PURPOSE: We have previously prospectively compared the differences in perioperative cardiac ischemic events in 140 patients undergoing major abdominal (n = 53) versus infrainguinal (n = 87) vascular operations. This study was designed to extend these observations by determining the 2-year cardiac prognosis of patients at high risk undergoing abdominal aortic versus infrainguinal vascular operations. METHODS: Data included historical, clinical, and laboratory data collected during the in-hospital period, and at 6 months, 1 year, and 2 years after surgery. This information was collected independently of the usual clinical care visits. Data were analyzed with Cox's proportional hazards model. RESULTS: There were 11 in-hospital deaths overall (five [9%] aortic; six [7%]) infrainguinal). 628 days (median 726 days). Fifteen patients (12%) had fatal myocardial infarctions, two (4%) of which occurred in patients who underwent aortic procedures and 13 (16%) of which occurred in patients who underwent infrainguinal operations. Nonfatal myocardial infarctions befell one (2%) patient undergoing aortic surgery and four (5%) patients undergoing infrainguinal surgery. One (2%) patient undergoing aortic surgery and three (4%) patients undergoing infrainguinal surgery were admitted to the hospital with unstable angina during the follow-up period. In all, adverse cardiac outcomes occurred in 20 of 81 (25%) patients who had infrainguinal procedures compared with four of 48 (8%) patients who had aortic operations (p = 0.04). Multivariate analysis showed that a history of diabetes (p = 0.001) and definite coronary artery disease (p = 0.01) are independently associated with adverse outcomes after both types of peripheral vascular operations. CONCLUSIONS: The incidence of long-term adverse cardiac outcomes in patients at high risk undergoing infrainguinal operations is substantially greater than in those undergoing aortic operations, mostly because of a greater prevalence of diabetes, and definite coronary artery disease in the former group.

Aged