Allan D. Callow

Vaccine-Induced Antibodies Inhibit CETP Activity In Vivo and Reduce Aortic Lesions in a Rabbit Model of Atherosclerosis

Using a vaccine approach, we immunized New Zealand White rabbits with a peptide containing a region of cholesteryl ester transfer protein (CETP) known to be required for neutral lipid transfer function. These rabbits had significantly reduced plasma CETP activity and an altered lipoprotein profile. In a cholesterol-fed rabbit model of atherosclerosis, the fraction of plasma cholesterol in HDL was 42% higher and the fraction of plasma cholesterol in LDL was 24% lower in the CETP-vaccinated group than in the control-vaccinated group. Moreover, the percentage of the aorta surface exhibiting atherosclerotic lesion was 39.6% smaller in the CETP-vaccinated rabbits than in controls. The data reported here demonstrate that CETP activity can be reduced in vivo by vaccination with a peptide derived from CETP and support the concept that inhibition of CETP activity in vivo can be antiatherogenic. In addition, these studies suggest that vaccination against a self-antigen is a viable therapeutic strategy for disease management.

Inhibition of neointimal hyperplasia by blocking αvβ3 integrin with a small peptide antagonist GpenGRGDSPCA

Abstract Purpose: Neointimal hyperplasia is a leading cause of restenosis after vascular procedures. Recent findings showed that smooth muscle cell (SMC) migration from the media into the neointima is a critical step in the development of the hemodynamically compromising neointimal lesion. Moreover, integrins are believed to play a role in SMC motility. Therefore we studied the role of one ubiquitous integrin, α v β 3 , in SMC migration. Methods: Transwell assay was used to study in vitro migration of human and rabbit SMCs after stimulation with platelet-derived growth factor (PDGF). A neutralizing monoclonal antibody to α v β 3 , LM609, and a specific arginine-glycine-aspartic acid (RGD) antagonist, G penGRGDSPC A, were used in the migration assay to inhibit α v β 3 -mediated SMC migration. In addition, G penGRGDSPC A was administered locally to rabbit carotidartery after balloon angioplasty to determine the effect of blocking α v β 3 on neointimal hyperplasia. Results: We showed that PDGF-induced human SMC migration is mediated by the α v β 3 integrin by use of LM609 to inhibit migration and that SMC migration is RGD dependent by use of G penGRGDSPC A to inhibit migration. We have also inhibited rabbit SMC migration with G penGRGDSPC A to demonstrate the cross-species preservation of the RGD peptide sequence in SMC mortality. Finally, when we administered G penGRGDSPC A locally to rabbit carotid artery after balloon angioplasty, there was a statistically significant reduction in neointimal lesion formation compared with arteries administered an inactive peptide or saline solution. Conclusions: We have demonstrated the important role of the α v β 3 integrin in SMC migration in vitro and in neointimal hyperplasia in vivo. (J VASC SURG 1994;19:125-34.)

A Controlled Study of the Prophylactic Portacaval Shunt: A Final Report

Abstract Ninety-three patients with cirrhosis and esophageal varices participated in a controlled prospective investigation of the prophylactic portacaval shunt procedure for the prevention of blee...

Candida infections in surgical patients.

Serious Candida infections were seen in 55 surgical patients from January 1977 through December 1980. Most of the patients had compromising underlying conditions and many were elderly. Broad-spectrum antibiotics and total parenteral nutrition (TPN) appeared to predispose patients to Candida infections. Mortality rate from Candida was 38%. A high percentage of patients with positive blood or bile cultures died as a result of Candida infection. Therapy with intravenous amphotericin B was highly effective if given in adequate dosage. No patient receiving more than 200 mg of amphotericin B died, but the mortality rate was 56% in those receiving lower doses.

Carotid endarterectomy contralateral to an occluded carotid artery: Perioperative risk and late results

To define better the short-term risk and long-term benefit of carotid endarterectomy opposite an occluded carotid artery, we reviewed our experience since 1961. Angiographic data are available for 598 of 670 (89.3%) patients in our carotid registry. In 63 (10.5%) patients the internal or common carotid artery on the side opposite the endarterectomy was occluded. All operations were carried out under general anesthesia with selective shunting based on electroencephalographic criteria. Shunting was required in 29 of 63 (46.0%) patients with contralateral occlusion and 72 of 535 (13.5%) control subjects (p less than 0.0001). Perioperative strokes occurred in 3 of 63 (4.8%) patients with contralateral occlusion and 14 of 535 control subjects (2.6%) (p = 0.23). Perioperative death occurred in 0 of 63 patients with contralateral occlusion and 6 of 535 (1.1%) control subjects (p = 0.40). Life-table cumulative stroke-free rates at 1, 5, and 10 years were 95.2%, 91.0%, and 76.2% in the group with contralateral occlusion and 96.0%, 89.4%, and 84.1% in control subjects (p = 0.25). Life-table cumulative survival rates at 1, 5, and 10 years were 93.1%, 80.8%, and 75.4% in the group with contralateral occlusion and 94.8%, 77.0%, and 57.9% in control subjects (p = 0.58). Carotid endarterectomy contralateral to an occluded carotid artery may be carried out with acceptable risk and late stroke-free and survival rates comparable to those seen in other patients who have undergone carotid endarterectomy.

Long-term results with the above-knee popliteal expanded polytetrafluoroethylene graft.

Since approximately 30% to 40% of autogenous vein bypass grafts to the femoropopliteal level may occlude within 5 years of implantation, additional vein will be required for subsequent revisions. We undertook a study to determine whether the preferential use of an above-knee expanded polytetrafluoroethylene bypass graft to save vein is an appropriate option. We reviewed our experience with 114 above-knee expanded polytetrafluoroethylene bypass reconstructions. Life-table analysis of primary and secondary graft patency was carried out by the method of Peto and statistically analyzed for the influence of clinical indication, runoff as determined by both preoperative and intraoperative completion arteriography, smoking, and diabetes. The 5-year primary patency rate of 57% for patients with claudication was comparable to contemporary randomized or retrospective series with below-knee autogenous vein for that indication, and it was superior to the patency rate for limb salvage. The status of the runoff vessels was an important determinant of outcome. The 59 limbs with good arteriographic runoff (2 to 3 vessels) had a markedly higher 5-year patency rate (70%) than the poor arteriographic runoff (0 to 1 vessels) group (30%). Continued cigarette smoking and diabetes mellitus also appeared to affect adversely primary graft patency in our hands. Our data support the use of preferential above-knee expanded polytetrafluoroethylene grafts in patients with good angiographic runoff. This approach does not appear to prejudice the limb against secondary revisionary procedures or the use of a new autogenous graft, if required.

Current management of amaurosis fugax

We present a consensus on the pathophysiology, etiology, diagnosis, and treatment of amaurosis fugax. The phenomenon is defined and described, and the roles that extracranial and ocular vascular diseases play are discussed. Nonvascular ophthalmic and neurologic disorders that can be confused with amaurosis fugax are listed, and an algorithm for evaluation (which includes ophthalmic examination, laboratory studies, and noninvasive carotid artery studies) is given. Treatment of atherosclerosis, carotid artery disease, and other causes of amaurosis fugax are also discussed.

Adult human endothelial cell coverage of small-caliber dacron and polytetrafluoroethylene vascular prostheses in vitro

Culture of endothelial cells on synthetic vascular grafts has heretofore met with limited success. We report here a technique which allows attachment and subsequent growth of adult human vascular endothelial cells on the synthetic materials polytetrafluoroethylene (PTFE) and Dacron which are currently used for vascular reconstructive surgery. Studies were conducted on both untreated materials and those pretreated with the extracellular matrix proteins collagen and fibronectin. Collagen was applied to the graft materials with positive pressure and then allowed to gel in the interstices. Fibronectin was added to the collagen-lined lumen followed by a cell suspension. Cell coverage on the grafts was assessed by scanning electron microscopy after various lengths of time. Cells adhered poorly to and did not grow on untreated Dacron and PTFE. Protein-treated materials did allow cell attachment and growth but with distinct differences. On PTFE (n = 30), cells could form a confluent monolayer within 9 days while cell coverage was generally incomplete at this time on the more irregular surface of Dacron (n = 5). Thus, adult human endothelial cells can grow on collagen- and fibronectin-coated prosthetic materials. This approach to lining graft materials in vitro may be useful in improving the performance of small-caliber vascular grafts.

Evaluation and performance standards for arterial prostheses

This report is one of a series of Reporting Standards generated by an Ad Ho c Committee of the Joint Councils o f the Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter. It is meant to address the needs of vascular surgery practitioners in their assessment of the merits of arterial prostheses, including methods of evaluation and expected performance. Although the standards described here are not mandatory, the Committee urges that at least minimally acceptable criteria be adopted by both manufacturers and regulatory authorities.

Cardiac risk in patients undergoing carotid endarterectomy: Impact on perioperative and long-term mortality

To identify patients undergoing carotid endarterectomy who are at high risk for cardiac events and death, we studied the course of 614 patients with known risk factors who were entered into our carotid follow-up registry. Patients were divided into two groups, group I with overt coronary disease (prior myocardial infarction, angina, significant electrocardiographic abnormalities) (N = 324) and group II without overt coronary disease (N = 290). Group II patients were subdivided into groups with (IIA) (N = 206) and without (IIB) (N = 84) coronary risk factors (cigarettes, diabetes, or hyperlipidemias). Thirty-day, 5-, 10-, and 15-year life-table survival for the groups was: I = 98.5%, 68.6%, 44.9%, 36.4%, respectively; II = 100%, 86.4%, 72.3%, 54.3%, respectively; IIA = 100%, 84.8%, 66.9%, 41.5%, respectively; IIB = 100%, 90.5%, 87.9%, 87.9%, respectively. Overt coronary disease was associated with diminished 30-day (p = 0.03) and late (p less than 0.0001) survival. Risk factors in the absence of overt disease were not associated with diminished 30-day survival. Late survival up to 3 years from endarterectomy was similar in groups IIA and IIB, but later survival was diminished in group IIA. Myocardial infarction was the most frequent cause of death in all groups. Patients with overt coronary disease are at high risk for late cardiac events and death. Patients without overt disease are at less risk than those with overt disease, and in the absence of overt disease, those without are at less risk than those with risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)