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Biomedical subjects

W M Abbott

Publications and source records attributed to W M Abbott.

At least 91 records · Page 5Linked to original sources

A laboratory model to quantitate the resistance of collagen vascular grafts to biodegradation.

Recent reports have shown that despite extensive preclinical testing, vascular grafts of biological origin undergo severe biodegradation and aneurysm formation after two or more years of implantation in man. The purpose of this study was to develop a laboratory model to quantitate and correlate the stability of crosslinked collagen grafts in vitro and in vivo. This resistance to biodegradation was assessed by measuring changes in suture pullout force and sample weight in response to controlled digestion with bacterial collagenase, in 0.5-cm-long cylindrical graft segments (chemically processed bovine carotid artery and human umbilical cord vein) that were implanted in the rat subcutis for 2 to 12 weeks. Scar tissue was removed from the explants by brief enzymatic digestion, a process that was inhibited when graft segments had become infected. Changes in dry weight were more consistent than were changes in wet weight; drying the graft segments had no effect on their degradation in vivo or in vitro. Intact cylindrical rings suffered somewhat less damage than did opened, flattened cylinders. Graft degradation increased markedly with implantation time, and was detected after only 3 weeks. We conclude that the rat subcutis model, when combined with controlled enzymatic digestion, first to remove scar tissue and then to challenge structural integrity, provides an accelerated assay by which to predict the stability of collagen vascular grafts.

Animals↗

Carotid surgery without arteriography: noninvasive selection of patients.

All carotid noninvasive studies at our institution comprised of duplex scanning, spectral frequency analysis, and ocular-pneumoplethysmography-Gee supraorbital Doppler assessments from 1985-1987 were reviewed. Forty symptomatic and 104 asymptomatic internal carotid arteries, concomitantly studied noninvasively and arteriographically, were identified. All studies were rereviewed prospectively and in blinded fashion. Utilizing peak frequency--internal carotid artery greater than 10 mHz and carotid index (Pf-ICA)/PF-common carotid) greater than 5 as criteria for surgery, 39/40 symptomatic internal carotid arteries were considered appropriate for carotid endarterectomy by noninvasive study. All of these internal carotid arteries had arteriographic confirmation of greater than 50% internal carotid artery stenosis; 22 of them met noninvasive criteria for surgery of peak systolic frequency-internal carotid artery greater than 14 mHz, carotid index greater than 7 and abnormal ocular-pneumoplethysmography-Gee/supraorbital Doppler. All of these had arteriographic confirmation of greater than 80% internal carotid artery stenosis. Eleven asymptomatic internal carotid arteries met spectral frequency criteria for carotid endarterectomy but had normal ocular-pneumoplethysmography-Gee/supraorbital Doppler. Eight in this group had less than 80% stenosis on arteriographic exam. Carotid endarterectomy may be performed without prior arteriography, provided objective criteria are established in a reliable noninvasive lab and met by individual patients.

Carotid Artery Diseases↗

Longterm study of a compliant biological vascular graft.

Clinically implanted prostheses of biological origin have recently been shown to develop aneurysms within several years. To study this process, recently developed bovine heterografts that were implanted in canine ilio-femoral arteries for 27 to 45 months, were studied in vivo and in vitro. Seven out of seven grafts were patent with only one showing evidence of focal aneurysm. Measurements of mechanical properties, including water permeability, compliance, and burst pressure, and of heat shrink temperature and dry weight were obtained before and after a period of controlled exposure to bacterial collagenase; all data suggested that much of the original graft had been replaced with host tissue. However, enzyme susceptibility was less than that of fresh bovine arteries, indicating that at least some of the grafts' crosslinked collagen was preserved. The compliance of these explants was similar to that reported for autogenous vein. Histological examination of the graft wall revealed cellular "intimal" and adventitial zones containing host-generated collagen surrounding a central zone devoid of cellular infiltration, which appears to be unmodified graft "media" highly resistant to degradation. We conclude that, when properly processed, biological prostheses can act as a bioresorbable scaffold for the orderly replacement of structural elements during healing, promoting continued mechanical integrity of the graft. These promising results encourage the further development of prostheses of biological origin.

Animals↗

Hypoxia induces procoagulant activity in cultured human venous endothelium.

Although it normally presents a nonthrombogenic surface, endothelium is capable of procoagulant activity and suppression of native anticoagulant properties. We theorized that hypoxia could shift normal endothelium into a procoagulant state and tested this hypothesis in cultured human umbilical venous endothelial cells. Human umbilical venous endothelial cells were obtained from fresh umbilical cords. Passage two cells were placed in control (PO2 greater than 120 mm Hg) or hypoxic (PO2 less than 60 mm Hg) media and incubated in control or hypoxic environments for 24 hours. In additional experiments, cells were reoxygenated for 4 or 48 hours after the initial hypoxic period. Cells were then assayed for procoagulant activity expressed as thromboplastin unit equivalents per 100,000 cells based on a thromboplastin standard curve. Results are expressed as percent increase in thromboplastin unit equivalents/100,000 cells +/- standard error versus control. Statistical significance was assessed by paired t test with p less than 0.05 considered significant. More than 95% of cells in all experimental and control preparations were viable after completion of the protocols. No morphologic variation was noted among the control and hypoxic groups. For cells rendered hypoxic without reoxygenation, the mean increase in procoagulant activity for the group (n = 4) versus control was 77% +/- 13% (p = 0.01). In the hypoxia and 4-hour reoxygenation group (n = 4), the mean increase in procoagulant activity was 141% +/- 43% (p less than 0.05). In cells reoxygenated for 48 hours after hypoxia (n = 8), the mean increase in procoagulant activity was 198% +/- 34% (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation↗

Delayed presentation and treatment of popliteal artery embolism.

In the course of reviewing a 10-year experience with popliteal artery embolism (PAE), two distinct patterns of clinical presentation were identified. In addition to those patients presenting with typical acute (symptom duration less than 7 days) arterial ischemia, a second group was identified who presented with more chronic symptoms. The present study was conducted to contrast the clinical factors and treatment of these two temporal patterns of presentation with PAE. Sixty PAEs in 58 patients were documented by the combination of angiography and/or exploration of the popliteal artery. Acute presentation (AP) was seen in 41 (68%) of these and delayed presentation (DP) was noted in 19 (32%) patients. Delayed presentation patients typically presented with a history of sudden onset of claudication or rest pain and a median symptom duration of 30 days. Eighty per cent of AP patients presented with immediately threatened limbs. Angiography was generally diagnostic of chronic popliteal embolism. In the acute group, 90% were treated with embolectomy alone, while 20% of the DP group required bypass grafting. However in two thirds of the DP group, embolectomy alone performed through a direct popliteal approach was possible. Current results with overall limb salvage (92%) and mortality (7%) represents a substantial improvement compared to the authors' previous experience with PAE. The current study suggests that as many as one third of patients with popliteal artery embolism may present in delayed fashion with chronic symptoms. Furthermore most of these patients can be treated with direct popliteal embolectomy alone with favorable results.

Amputation, Surgical↗

Spontaneously hypertensive and Wistar Kyoto rats are genetically disparate.

Spontaneously hypertensive rats (SHR) are one of the most common animal models used to study essential hypertension in humans. Because SHR and normotensive Wistar Kyoto (WKY) rats were both established from the same parental, normotensive Wistar stock, WKY animals have been used almost exclusively as control animals in studies of SHR. Recently, the suitability of WKY rats as normotensive controls for SHR has been challenged. To establish whether or not SHR and WKY rats share the same immunologic backgrounds, we initially performed a series of skin grafting experiments on these animals. In all cases, grafts of SHR donor skin to WKY recipients and of WKY donor skin to SHR recipients resulted in complete rejection within 7 to 10 days. In addition, grafts of WKY donor skin to other WKY recipients resulted in graft rejection. By contrast, skin grafts between SHRs were always accepted. To further characterize the genetic distinctions between SHR and WKY rats, allelic profiles based on a series of immunologic and biochemical markers were established for each strain. These findings clearly establish that SHR and WKY rats differ at the major histocompatibility complex, in specific blood group antigens, and in a panel of isozymic markers. Moreover, whereas SHRs have the same genetic profiles irrespective of source, some colonies of WKY rats are outbred, as judged by their variant allelic profiles.

Animals↗

Intestinal ischemia complicating abdominal aortic surgery.

A 9-year experience with 2137 patients undergoing infrarenal abdominal aortic reconstruction was reviewed to determine both the incidence of intestinal ischemia and the clinical, anatomic, and technical factors associated with this complication of aortic surgery. A total of 24 (1.1%) patients had overt intestinal ischemia, documented by reoperation or endoscopic findings. Of these, colon ischemia occurred in 19 (0.9%) and small bowel ischemia developed in 5 (0.2%) patients. The incidence after elective operation for aneurysmal or occlusive disease did not differ, but patients with ruptured aneurysms and those undergoing reoperative procedures for total graft replacement were at higher risk. Preoperative angiography was most helpful in ascertaining risk. Ligation of a patent inferior mesenteric artery was the most common (74%) feature in patients with colon ischemia. With preexisting inferior mesenteric artery occlusion, impairment of collateral circulation was attributable to superior mesenteric artery disease, dissection or retractor injury, prior colon resection, or exclusion of hypogastric perfusion. Bloody diarrhea was the most frequent postoperative symptom and colonoscopy the most reliable means of diagnosis. One half of patients with colon ischemia required resection after late recognition of perforation. All cases of small bowel ischemia were related to superior mesenteric artery disease or injury or use of suprarenal clamping. The overall mortality rate was 25% but rose to 50% if bowel resection was required. Intestinal ischemia remains an infrequent but serious complication of aortic surgery. Despite a multifactorial cause, identification of patients at increased risk can lead to operative strategies to reduce its occurrence.

Aged↗

Aortocaval and iliac arteriovenous fistulas: recognition and treatment.

Despite the well characterized physiologic effects of aortocaval or iliac arteriovenous fistulas, patients with such uncommon lesions may manifest a diverse array of symptoms, and diagnosis is often delayed or overlooked. To examine clinical features that facilitate recognition and allow successful repair, a 30-year experience with 20 such fistulas was reviewed. Fourteen fistulas were caused by aneurysm erosion, four followed iatrogenic injury during lumbar disk surgery, and two developed from abdominal gunshot wounds. The interval from presumed occurrence to diagnosis ranged from 3 hours to 8 years. The diagnosis was not recognized before surgery in five (25%) patients. Back pain (70%) was the most common symptom. The presence of a typical abdominal bruit (80%) was the most reliable physical finding, but its significance was occasionally overlooked or misinterpreted. Congestive heart failure was prominent in only seven (35%) patients. Severe lower extremity edema and mottling was the primary manifestation in eight cases, often causing initial confusion with venous thrombosis. Hematuria (5 patients) and oliguric renal failure (4 patients), both fully reversible after fistula repair, also caused diagnostic uncertainty. The mean preoperative cardiac output was 12.2 L/min, falling to 5.4 L/min with fistula repair. Mean blood loss was 5960 ml, supporting use of intraoperative autotransfusion. Two operative deaths (10%) occurred, both in patients not correctly diagnosed before surgery. Despite varied modes of presentation, prompt recognition and use of appropriate operative techniques should achieve successful repair.

Adult↗

Transperitoneal versus retroperitoneal approach for aortic reconstruction: a randomized prospective study.

A prospective, randomized study was conducted to compare the retroperitoneal versus transperitoneal approach for elective aortic reconstruction. One hundred thirteen patients (transperitoneal = 59, retroperitoneal = 54) were randomized between March 1987 and October 1988. In addition, to assess the changing course of patients undergoing aortic reconstruction similar data were gathered retrospectively on a group of 56 patients undergoing aortic reconstruction by the same surgeons performed via a transperitoneal approach in 1984 to 1985. Randomized patients were identical in age, male to female ratio, smoking history, incidence and severity of cardiopulmonary disease, indication for operation, and use of epidural anesthetics. Details of operation including operative and aortic cross-clamp times, crystalloid and transfusion requirements, degree of hypothermia on arrival at the intensive care unit, and perioperative fluid and blood requirements did not differ significantly for patients undergoing transperitoneal versus retroperitoneal reconstruction. Respiratory morbidity, as assessed by percent of patients requiring postoperative ventilation, deterioration in pulmonary function tests, and the incidence of respiratory complications, was identical in randomized patients. Other aspects of postoperative recovery including recovery of gastrointestinal function, the requirement for narcotics, metabolic parameters of operative stress, the incidence of major and minor complications, and the duration of hospital stay were similar for randomized patients undergoing transperitoneal and retroperitoneal reconstruction. When compared to retrospectively reviewed patients having aortic reconstruction, randomized patients undergoing transperitoneal and retroperitoneal operations had highly significant (p less than 0.001) reductions in postoperative ventilation, transfusion requirements, and length of hospital stay. Such trends were all independent of transperitoneal versus retroperitoneal approach.(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta, Abdominal↗

Aberrant right subclavian artery: varied presentations and management options.

Although an aberrant right subclavian artery arising from the proximal portion of the descending thoracic aorta is the most common aortic arch anomaly, few patients have clinical symptoms directly attributable to it. When symptoms do occur they are usually causally related to aneurysmal or occlusive sequelae of atherosclerotic disease of the anomalous vessel. More unusual manifestations peculiar to the anomalous artery include aneurysmal degeneration of the origin of the vessel from the aortic arch, with its inherent risk of rupture, or symptoms of compression of the trachea or more commonly the esophagus by the anomalous vessel as it traverses the superior mediastinum. In patients with symptoms a variety of operative approaches and management strategies have been used. Our recent experience with treatment of two patients with clinical symptoms caused by an aberrant right subclavian artery illustrate the varied surgical options and prompted a review of the surgical management of this unusual anomaly.

Adult↗

Soluble bovine galactose-binding lectin. cDNA cloning reveals the complete amino acid sequence and an antigenic relationship with the major encephalitogenic domain of myelin basic protein.

A full-length cDNA clone for the 13-14 kDa soluble beta-galactoside-binding lectin was isolated from a bovine fibroblast cDNA library. The derived amino acid sequence shows eight differences from a preliminary partial amino acid sequence given previously for the bovine heart lectin. This observation led to a re-examination of the data and correction of the heart lectin protein sequence. Except for a possible polymorphism of the heart lectin at position 57, the fibroblast and heart lectin sequences are considered identical. The epitope recognized by two monoclonal anti-(bovine lectin) antibodies, 36/8 and 9/5, was identified as the tetrapeptide sequence W-G-A/S-E/D by the isolation of several different cDNA clones from a human intestine cDNA library. A similar tetrapeptide is present in all of the soluble beta-galactoside-binding animal lectins sequenced thus far. It is also found in myelin basic protein, which we show is antigenically cross-reactive with the lectin. In myelin basic protein the tetrapeptide is a part of the major domain previously shown to be responsible for the induction of experimental allergic encephalomyelitis.

Amino Acid Sequence↗

Evidence that the 14 kDa soluble beta-galactoside-binding lectin in man is encoded by a single gene.

A full-length cDNA clone for the 14 kDa soluble beta-galactoside-binding lectin of man has been isolated from a cDNA library from HepG2 hepatoma cells. The derived amino acid sequence is identical with that of the 14 kDa lectin from human placenta. The results of Northern and Southern blotting of several different human cell lines using a cDNA probe for the 14 kDa lectin suggest the presence of a single gene for this protein. Thus, although there are multiple proteins in the range 14-200 kDa which are antigenically related to this lectin, we would conclude from the present study that there is only one gene for the 14 kDa lectin.

Amino Acid Sequence↗

Recent experience with thoracoabdominal aneurysm repair.

Thoracoabdominal aneurysm repair was carried out in 55 patients during the period from January 1978 to June 1988. Considering the volume of experience and application of a routine for preoperative and intraoperative management, the experience was divided as follows: group 1 1978 to 1985 (26 patients) and group 2 1985 to 1988 (29 patients). Clinical features of the two groups differed only in the incidence of emergency operations (group 1 [6/18, 30%] vs group 2 [2/29, 8%]). Operative mortality in elective operations improved substantially in recent experience (group 1 [50%] vs group 2 [7.4%]). Significant reductions in total operative time, operative blood loss, and total aortic cross-clamping times paralleled and, in part, explained the improvement in overall surgical results seen in group 2 patients. Spinal cord injury occurred in 7.2% of the entire cohort. Nonfatal but major complications occurred in 25% of group 2 patients, with the most common being prolonged ventilatory assistance (12%). Current results with thoracoabdominal aneurysm repair both establish its safety and help to provide guidelines in selecting patients for elective repair.

Acute Kidney Injury↗

Fibronectin enhances early shear stress resistance of seeded adult human venous endothelial cells.

An in vitro parallel plate perfusion chamber was used to study the shear stress resistance of seeded adult human saphenous vein endothelial cells (AHSVECs) on glass surfaces coated with different substrates. Endothelial cells were seeded onto glass slides precoated with these substrates and then exposed to pulsatile flow with an average shear stress of 8 dyn/cm2 for 1 hr. After AHSVEC attachment periods of 15 min, 1 hr, and 2 hr, flow dislodged all but 1.4, 30.4, and 72.2%, respectively, of cells that had been seeded onto 1% gelatin. Control slides that were not exposed to flow retained 12.9% (P less than 0.03), 49.8% (NS), and 95.2% (NS) of seeded cells. Precoating the slides with 10 micrograms/ml fibronectin resulted in 69.4, 89.5, and 97.7% of cells remaining after flow, compared with 6.4% (P less than 0.03), 53.7% (NS), and 93.3% (NS), respectively, when using matched slides coated with 1% gelatin. Results with 20% fetal bovine serum as the substrate were not statistically different from those obtained with 1% gelatin. We conclude that fibronectin enhances the early attachment of AHSVECs to artificial surfaces and is, therefore, potentially useful for increasing attached cell yields on arterial prostheses prepared with immediate cell seeding techniques.

Cell Adhesion↗

Response of skin photoplethysmography, laser Doppler flowmetry and transcutaneous oxygen tensiometry to stenosis-induced reductions in limb blood flow.

Photoplethysmography (PPG), transcutaneous oxygen tensiometry (TCpO2) and laser Doppler flowmetry (LDF) were used to measure changes in perfusion of the distal lower limb of the pig, in response to a stenosis created in the external iliac artery. The severity of stenosis was quantitated by the ratio of peak systolic distal pressure to peak systolic proximal pressure (distal systolic pressure index, DSPI). PPG and LDF were immediately responsive to changes in perfusion pressure while TCpO2 responded much more slowly. PPG dropped precipitously in response to even a small reduction in perfusion pressure, reaching zero at a DSPI of approximately 0.3. TCpO2 was insensitive to the presence of a mild stenosis (DSPI greater than 0.6), but was highly sensitive in the range 0.6 greater than DSPI greater than 0.3. At lower DSPI values, TCpO2 also became zero, due in part to electrode consumption of oxygen. LDF readings were sensitive to changes in blood flow throughout the entire range of stenosis, down to the point of total occlusion, although changes were not significant at DSPI values greater than 0.6. Because LDF measures not only nutritional blood flow, but flow in AV shunts and subdermal plexuses as well, high LDF readings could erroneously suggest tissue viability and good healing potential. Resting levels of TCpO2 and LDF can be used to follow the progress of peripheral vascular disease, and used complementarily, in many cases, to evaluate the severity of flow impairment.

Animals↗