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Biomedical subjects

A D Callow

Publications and source records attributed to A D Callow.

At least 37 records · Page 2Linked to original sources

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.

Arterial Occlusive Diseases↗

The vascular endothelial cell as a vehicle for gene therapy.

Increasing knowledge that has accumulated during the past decade reveals that the endothelial cell plays a far larger role than that traditionally assigned to it, namely maintenance of the fluid state of the blood. Unraveling the complex interreactions of the endothelial cell with the other cellular and molecular components of the arterial wall, as well as with the blood and its cellular and particulate components, is leading to better understanding of anastomotic hyperplasia and recurrent stenosis after endarterectomy and balloon angioplasty. More recently with the newly acquired techniques of inserting genetic material into the vascular endothelial cell many new therapeutic possibilities may be developed. Important to the technique of seeding vascular grafts, and the possible use of the genetically modified endothelial cell for gene therapy systems, are the needs to identify the origin of the cell originally seeded and ways to increase their number. Retroviral vectors and genetically conferred antibiotic resistance provide these means.

Animals↗

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.

Adult↗

Scanning electron microscopy analysis of polyethylene oxide hydrogels for blood contact.

Hydrogels are a class of synthetic material, composed of a polymer-water matrix and have been proposed as tissue substitutes and drug delivery vehicles. Polyethylene oxide (PEO) hydrogels were synthesized and used to produce coated wires and conduits for baboon blood compatibility studies. Blood-material interactions were studied both by Scanning Electron Microscopy (SEM) and 111In labeled platelet deposition. SEM processing modifications were first evaluated in order to reduce shrinkage and surface distortion incurred during sample preparation of these high water content materials. Pretreatment with 1% tannic acid reduced bulk shrinkage associated with critical point drying by 10-20%. This effect is small, nevertheless, it prevented major sample disruption. Coated guidewires were exposed to baboon blood for one hour in the inferior vena cava and conduits were placed for either 30 or 60 minutes in an ex vivo femoral arteriovenous shunt. Reference materials included Gore-tex, polyethylene and silica-free polydimethyl siloxane (PDMS). In the guidewire studies, 111In labeled platelet levels were highest on Gore-tex (6568.97 platelets/1000 microns 2) and large thrombotic deposits were well visualized by SEM. Formulations containing PEO had low levels of platelet deposition and little evidence of platelet activation was noted by SEM. Shunt studies demonstrated that materials of high PEO content and molecular weight had the lowest levels of platelet deposition. After 60 minutes of blood flow, mean platelet deposition on PDMS and Gore-tex was 50 and 1000 fold higher than on a network composed of 65% PEO 20,000 (p less than 0.05). SEM confirmed these findings.

Analysis of Variance↗

Implantation of vascular grafts lined with genetically modified endothelial cells.

The possibility of using the vascular endothelial cell as a target for gene replacement therapy was explored. Recombinant retroviruses were used to transduce the lacZ gene into endothelial cells harvested from mongrel dogs. Prosthetic vascular grafts seeded with the genetically modified cells were implanted as carotid interposition grafts into the dogs from which the original cells were harvested. Analysis of the graft 5 weeks after implantation revealed genetically modified endothelial cells lining the luminal surface of the graft. This technology could be used in the treatment of atherosclerosis disease and the design of new drug delivery systems.

Animals↗

The effect of radiofrequency-generated thermal energy on the mechanical and histologic characteristics of the arterial wall in vivo: implications for radiofrequency angioplasty.

Abrupt reclosure of atherosclerotic vessels after percutaneous transluminal balloon angioplasty has been blamed on traumatic dissections and elastic recoil of the vessel wall. Thermal energy with compression produces fusion of separated arterial wall layers, and heat appears to alter the elastic recoil of the vessel wall. Radiofrequency (RF) thermal energy has been used to perform vascular anastomoses and thermal angioplasty. A simple in vivo experiment was designed to describe and quantitate vascular tissue weld strength produced by a range of RF thermal energy levels. Canine carotid arteries were compressed between a pair of modified bipolar forceps that applied RF energy, causing occlusive tissue welds between the apposed intimal surfaces. The strength of the welds was evaluated by measuring the perfusion pressure required to reopen the vessel lumen. A dosimetry range of 0 to 205 joules showed a typical dose-response curve for the relationship between energy applied and bond strength, plateauing at approximately 300 mm Hg. Light microscopy showed fusion of the inner surfaces of the vessel with preservation of vessel wall architecture. Additionally inflation of a bipolar RF balloon catheter in the normal canine carotid lumen produced an alteration of vessel profile angiographically and histologically. Results of these preliminary experiments suggest that balloon angioplasty with adjunctive RF thermal energy may have benefits in reducing the factors causing acute failure of conventional percutaneous transluminal balloon angioplasty.

Angiography↗

Development and evaluation of a new polymeric material for small caliber vascular prostheses.

Polyethylene oxide (PEO), because of its low levels of protein and cellular adsorption, may provide a suitable coating for synthetic small caliber vascular prostheses. PEO/polysiloxane networks were synthesized via an acid-catalyzed epoxy/hydroxyl crosslinking reaction and used to produce conduits with a 4-mm internal diameter. Three networks with nominal PEO molecular weights of 2000, 8000, and 20,000 and all 65% PEO by weight were studied. Blood compatibility was assessed by measuring 111In-platelet and 125I-fibrinogen deposition in a baboon ex vivo shunt, over a 1-hr time period and at a flow rate of 50 ml/min. Differences in material performance were noted particularly after the initial 30-min blood contact period. Materials in the mid and high PEO molecular weight range (8000 and 20,000) had significantly lower levels of platelet adsorption than networks of low PEO molecular weight (2000) at 30 min (P less than 0.005) and 60 min (P less than 0.05). The lowest level of platelet deposition was noted on networks of high PEO molecular weight (20,000). During the observation period, platelet accumulation on this surface was less than one platelet per 1000 microns. Platelet deposition on Gore-Tex was two and three orders of magnitude greater than that on the high molecular weight PEO material at 30 and 60 min, respectively (P less than 0.001). Fibrinogen adsorption was also lower on materials of mid and high PEO molecular weights, when compared with low molecular weight networks (P less than 0.05) and Gore-Tex (P less than 0.05). Scanning electron micrographs confirmed these observations. Overall, platelet and fibrinogen depositions are low for PEO networks, particularly for materials of high PEO molecular weight. This latter observation may be related to increased surface molecular mobility and a relative enhancement of PEO content at the blood-material interface.

Animals↗

Observations on human smooth muscle cell cultures from hyperplastic lesions of prosthetic bypass grafts: production of a platelet-derived growth factor-like mitogen and expression of a gene for a platelet-derived growth factor receptor--a preliminary study.

Prosthetic bypass grafts placed to the distal lower extremity often fail because of an occlusive tissue response in the perianastomotic region. The origin of the cells that comprise this occlusive lesion and the causes of the cellular proliferation are not known. To increase our understanding of this process we cultured cells from hyperplastic lesions obtained from patients at the time of reexploration for lower extremity graft failure, and we studied their identity and growth factor production in tissue culture. These cultures contain cells that express muscle-specific actin isoforms, shown by immunohistochemical staining, consistent with vascular smooth muscle origin. These cultures also released material that stimulated smooth muscle cell growth. A portion of this activity was similar to platelet-derived growth factor, since preincubation with antibody-to-human platelet-derived growth factor partially blocked the mitogenic effect of medium conditioned by human anastomotic hyperplastic cells. These conditioned media also contained material that competed with platelet-derived growth factor for its receptor, as measured in a radioreceptor assay. Northern blot analysis showed that these cells contain messenger RNA that encodes the A chain but not the B chain of platelet-derived growth factor. In addition, these cells contain messenger RNA that encodes a platelet-derived growth factor receptor. We conclude that cultured smooth muscle cells from human anastomotic hyperplastic lesions express genes for platelet-derived growth factor A chain and a platelet-derived growth factor receptor and secrete biologically active molecules similar to platelet-derived growth factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Long-term follow-up of surgically managed carotid bifurcation atherosclerosis. Justification for an aggressive approach.

To document the efficacy of our aggressive surgical approach to stroke prevention, we compiled follow-up data on 619 patients undergoing 993 carotid endarterectomies at our institution since 1970. Following carotid endarterectomy, crude annual stroke incidence, including perioperative strokes (2.2%), was 1.9%. In our symptomatic patients crude annual stroke incidence, including perioperative strokes (2.7%), was 2.1%. This is superior to the annual stroke incidence seen in patients on "optimal" medical therapy as defined by the Canadian Cooperative Study (4.6% in men), the AICLA Study (2.9%), the American Multicenter Trial (8%), and the Canadian- American Cooperative Trial (approximately 5%). In our asymptomatic patients, crude annual stroke incidence, including perioperative strokes (1.1%), was 1.4%. This is superior to nonsurgical therapy for asymptomatic patients with hemodynamically significant or more than 75% stenoses as reported by the Mayo Clinic (3.4%) or Chambers and Norris (2.7%). An aggressive surgical approach to carotid bifurcation atherosclerosis is superior to nonsurgical therapy in symptomatic and selected asymptomatic patients if low perioperative mortality/stroke morbidity rates are achieved.

Actuarial Analysis↗

Carotid endarterectomy in patients with intracranial vascular disease: short-term risk and long-term outcome.

To determine the influence of angiographically identifiable intracranial vascular lesions on the outcome of carotid endarterectomy, 597 patients from our carotid surgery registry who had had complete angiographic evaluation were divided into two groups: (1) significant intracranial disease identified by angiography (N = 134) and no significant intracranial disease identified by angiography (N = 463). The short- and long-term outcomes of carotid endarterectomy in the two groups were compared. Perioperative stroke morbidity (intracranial disease 1.9%, no intracranial disease 1.8%) and mortality (intracranial disease 0.5%, no intracranial disease 0.7%) were acceptable and not statistically different (p greater than 0.7). Late stroke prevention was nearly identical in the two groups, with 3-, 5-, and 10-year life-table of stroke-free rates of 93%, 87%, and 79%, respectively, versus 92%, 90%, and 85%, respectively, in the intracranial disease and no intracranial disease groups (p = 0.75). The incidence of recurrent transient ischemic attack was 9.7% in the intracranial disease group and 6.5% in the no intracranial disease group (p = 0.22). In the clinical population studied in the described method, angiographically identifiable intracranial vascular disease did not appear to have a statistically demonstrable influence on the short-term or long-term prognosis after carotid endarterectomy.

Brain Ischemia↗

Carotid endarterectomy: what is its current status?

The plethora of recent articles regarding carotid endarterectomy has tended to confuse rather than clarify its indications, efficacy, and acceptability. The National Institutes of Health has recently funded two large multicenter controlled clinical trials, one including asymptomatic persons with carotid stenoses, and the other, patients having transient ischemic episodes or minor strokes. Eight academic professors of neurology (four), neurosurgery (two), and vascular surgery (two) with a long and abiding interest in cerebrovascular disease prepared a statement delineating acceptable levels of mortality and morbidity from this procedure. These might serve as guidelines until the large trials have been completed.

Arteriosclerosis↗

A new primate model for the study of intravenous thrombotic potential and its modification.

Advances in venous reconstruction have been limited by inherent venous thrombogenicity and the absence of a suitable prosthetic material for use in the venous system. We have designed an in vivo experimental model to evaluate early blood-material interactions within the venous system and to quantitate drug efficacy in the alteration of platelet function and fibrin deposition in the baboon. An 8F catheter was placed percutaneously in the femoral vein of an adult male baboon. Indium 111-labeled autogenous platelets or iodine 125-labeled human fibrinogen was infused before the introduction, into the inferior vena cava, of a linear array of 5 x 15 mm alternating Dacron and polytetrafluoroethylene samples attached to a benzalkonium-heparin-treated guide wire. At 60 or 120 minutes the samples were removed and a 1 ml aliquot of blood was drawn. The materials and blood samples were counted in a gamma well counter, and the material counts were normalized to the circulating label present in the 1 ml blood sample. The experiment was repeated after pretreatment with heparin, aspirin, or dextran. Whole blood clotting times and bleeding times were monitored. The results showed decreased platelet and fibrin deposition on polytetrafluoroethylene when compared with Dacron in the venous system. Aspirin, heparin, and dextran were all found to decrease platelet and fibrin deposition onto intravenously placed graft material samples (p less than 0.05, Student's t test). The data confirm the ability of the model to evaluate quantitatively anticoagulants, antiplatelet agents, and prospective graft materials for use in venous reconstructions.

Animals↗

The systemic activation of platelets by Dacron grafts.

Dacron (polyester fiber), a stimulus to platelet aggregation in vitro, accumulates platelets to a greater extent in vivo than autogenous artery, polytetrafluoroethylene (PTFE) or human umbilical vein (HUV). We conducted a series of experiments using the ex vivo shunt in the baboon to determine whether or not systemic activation of platelet function was produced by a Dacron graft. Two 5 centimeter segments of 4 millimeter internal diameter graft materials were placed in series in the ex vivo shunt perfused at 25 milliliters per minute flow rate for two and one-half hours. Deposition of autologous Indium 111 labeled platelets was monitored. The ex vivo shunt procedures were divided into two groups, both with PTFE as the proximal graft: one with a distal Dacron graft (n = 21), the second with PTFE or HUV distally (n = 17). In this study, an increase in platelet deposition on the proximal PTFE graft represents systemic platelet activation caused by the distal graft. Increased platelet deposition on PTFE was noted at all time points in the presence of a Dacron graft (p less than 0.05). This property of Dacron has important clinical implications, potentially accelerating the progression of vascular disease, increasing the failure rate of composite grafts and subsequent arterial reconstruction.

Animals↗

Hemodynamics and prostacyclin release in the early phases of aortic surgery: comparison of transabdominal and retroperitoneal approaches.

Although the retroperitoneal aortic approach (RP) is advocated to reduce myocardial ischemia and cardiac-related death, inadequate physiologic data exist to support this contention. As the aorta is exposed via the transabdominal approach (TA) we noted some patients have manifested reduced systemic vascular resistance (SVR) associated with tachycardia, reduced blood pressure, and facial flushing. To determine whether RP offered physiologic advantages over TA we compared cardiac dynamics and blood levels of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), the stable metabolite of prostacyclin, during exposure of the aorta in 52 patients (33 with TA and 19 with RP), comparable in age, cardiac history, medications, and body surface area. Serial measurements of mean arterial pressure, heart rate, wedge pressure, pulmonary artery pressure, cardiac index, and 6-keto-PGF1 alpha were obtained. Results revealed decreased mean arterial pressure and systemic vascular resistance, increased cardiac index and heart rate, and facial flush occurring 10 minutes after the bowel was explored in TA. This was not observed in RP. These hemodynamic alterations correlated in time and magnitude with a fourteen fold increase in 6-keto-PGF1 alpha. These changes in cardiac indexes can produce increased myocardial oxygen consumption with the risk for myocardial ischemia, particularly in patients with coronary artery disease. The absence of this response to bowel exploration in RP may account for some of the observed advantages in "high-risk" aortic reconstruction.

6-Ketoprostaglandin F1 alpha↗

Clinical, hemodynamic, and anatomic follow-up of direct venous reconstruction.

Conventional therapy for the advanced clinical stages of the postthrombotic syndrome is associated with recurrence of symptoms and ulcer. Direct venous reconstruction may relieve the symptoms of patients with either iliac vein obstruction or valvular incompetence, but there are few reports detailing late hemodynamic and anatomic findings. We summarized the clinical, hemodynamic, and anatomic follow-up of six patients with saphenofemoral bypass (SFB) and ten patients with axillary vein valve-to-popliteal vein transplants (PVTs) who were followed up for a minimum of two years. All ten ulcers in the PVT group healed and symptoms of venous claudication, limb swelling, and all ulcers healed in the SFB group. Late (greater than 2 years) anatomic and functional assessment showed that the SFB bypasses were patent and the PVTs were both patent and functional.

Adult↗

The management of early in situ saphenous vein bypass occlusions.

To determine the causes and optimum management of early in situ bypass occlusions, we reviewed our experience of 13 thromboses occurring within the first 30 postoperative days in 148 in situ saphenous vein reconstructions. All early thrombosed bypasses were performed for limb salvage, with 31% of bypasses to the popliteal level and 69% to infrapopliteal vessels. The median time to occlusion was 24 hours. All patients underwent reoperation. Graft failure was due to retained venous valves in 31% of the procedures, other technical problems in 38%, and inadequate outflow in 31%. Reoperative surgery was individualized. In grafts explored for thrombosis, the one-year graft patency rate was 46%, and the limb salvage rate was 54%. Graft patency did not appear to correlate with the presumed cause of initial graft occlusion. Our results indicate that an aggressive surgical approach is appropriate in early in situ graft thrombosis.

Humans↗

The effect of low molecular weight dextran on platelet deposition onto prosthetic materials.

Low molecular weight dextran (LMD) has recently been shown in a randomized, multicenter trial to improve early patency in difficult lower extremity vascular bypass. The question remained as to whether this effect was due to plasma volume expansion by LMD or to its effects on platelets and coagulation. To analyze this we have studied the effects of LMD on platelet-graft interactions using an ex vivo baboon shunt. Indium 111-labeled autologous platelet deposition on expanded polytetrafluoroethylene and knitted Dacron grafts was monitored at a flow rate of 25 ml/min for 21/2 hours. LMD was given by intravenous bolus at a dose of 5 ml/kg and was followed by a continuous infusion of 10 ml/hr. Flow through the shunt was started after the initial dextran bolus. Control studies were performed in a similar manner without dextran. An additional series of experiments was performed with a 5 to 10 ml/kg bolus of 5% human serum albumin to analyze the contribution of plasma volume expansion to platelet deposition in this model. The results revealed a significant (p less than 0.05) reduction in platelet deposition on both graft materials with the LMD infusion. No difference was seen between the control group and the albumin group. These studies provide direct in vivo evidence of the antiplatelet effect of LMD.

Albumins↗