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Biomedical subjects

M G Walker

Publications and source records attributed to M G Walker.

At least 55 records · Page 3Linked to original sources
PubMed1992

The response of rapidly formed adult human endothelial-cell monolayers to shear stress of flow: a comparison of fibronectin-coated Teflon and gelatin-impregnated Dacron grafts.

Endothelial cells labeled with indium 111-oxine were seeded in supraconfluent densities onto fibronectin-coated expanded polytetrafluoroethylene (ePTFE) and gelatin-impregnated Dacron graft segments. These grafts with rapidly formed endothelial-cell monolayers were then exposed to varying shear stresses at flow rates of 200 and 300 ml/min, using tissue culture medium in an artificial flow circuit. As the loss of radioactivity represented endothelial-cell loss, cell retention was calculated by the ratio of counts recorded at different time points during 2 hours of flow to initial counts. Although initial cell adherence to gelatin-impregnated Dacron graft segments was poor compared to ePTFE, once cells were attached they resisted shear stress of flow better at 200 ml/min and equally well at 300 ml/min. The cell retention on fibronectin-coated ePTFE was 55.4 +/- 12.9% at 200 ml/min and 56.5 +/- 15.2% at 300 ml/min; cell retention for gelatin-impregnated Dacron graft segments was 69.0 +/- 6.0% and 66.5 +/- 5.5%, respectively. Qualitatively scanning electron microscopy of both ePTFE and gelatin-impregnated Dacron graft segments showed patchy coverage of grafts with cells. There was preferential attachment of endothelial cells to the nodes on ePTFE, although on gelatin-impregnated Dacron graft segments, cells conformed to the Dacron fibers at different levels and directions with evidence of bridging in the gaps between individual fibers. This study shows conclusively that rapidly formed endothelial-cell monolayers on ePTFE and gelatin-impregnated Dacron graft segments resisted a shear stress of flow equal to that seen in a femoropopliteal vein graft with significant cell retention at 2 hours.

Blood Vessel Prosthesis↗
PubMed1991

Comparison of different vascular prostheses and matrices in relation to endothelial seeding.

Thin-walled expanded polytetrafluoroethylene (ePTFE), woven Dacron and gelatin-impregnated Dacron (Gelseal) vascular grafts were compared, the grafts being coated with three different matrices: collagen IV, fibronectin and preclot matrix. In addition, untreated ePTFE and Gelseal were examined. The graft segments, coated with these matrices, were incubated with radiolabelled adult human endothelial cells for 30, 60 and 90 min. Endothelial cell adherence was calculated from the ratio of radioactive counts in the grafts to counts in grafts plus supernatants. Endothelial cell attachment to untreated grafts was poor, but a suitable matrix significantly improved adherence. All three matrices tested gave good results, although preclot was best; 30-60 min incubation was sufficient for optimum cell attachment. Cell adherence to both Dacron and ePTFE was significantly better than to Gelseal. The type of prosthetic polymer and the substrate protein coating used to promote endothelial cell adherence are two important factors which may determine the ultimate success of endothelial seeding in the operating room.

Blood Vessel Prosthesis↗
PubMed1991

True profunda femoris aneurysms: are they more dangerous than other atherosclerotic aneurysms of the femoropopliteal segment?

Three cases of true aneurysms of the profunda femoris artery are reported along with a review of 17 other cases in the literature. These aneurysms are rare and commonly present with rapid enlargement or rupture (9/20), the risk of rupture being higher than those affecting the femoral or popliteal arteries. All patients underwent successful surgical treatment except for one who required amputation. The diagnosis of an aneurysm of the profunda femoris artery must be considered in all patients with a pulsatile swelling in the groin. Surgical treatment is mandatory, and it carries a low mortality as well as a low risk of amputation.

Aged↗
PubMed1991

In vitro adherence and kinetics studies of adult human endothelial cell seeded polytetrafluoroethylene and gelatin impregnated Dacron grafts.

Lining the luminal surface of small diameter vascular prostheses with living endothelial cells reduces thrombogenicity, decreases infection and improves patency. In vitro adherence and kinetics studies of adult human endothelial cell seeded Polytetrafluoroethylene (ePTFE) and Gelatin impregnated Dacron (Gelseal) were performed. Endothelial cell adherence on ePTFE and Gelseal coated with collagen IV, fibronectin and preclot matrices was compared. Untreated ePTFE and Gelseal were also used. Ten graft segments in each group coated with these matrices were incubated with radio-labelled adult human endothelial cells for 30, 60 and 90 min. Labelled endothelial cells seeded in supra-confluent densities on fibronectin coated ePTFE and Gelseal grafts were used for kinetic studies. Resultant endothelial cell monolayers were then exposed to varying shear stress at flow rates of 200 and 300 ml/min in an artificial flow circuit. Endothelial cell attachment to untreated grafts was poor and a suitable matrix significantly improved adherence with fibronectin and preclot but less so with collagen. A 30 min incubation was sufficient for optimum cell attachment. Cell adherence to ePTFE was significantly better than Gelseal. Scanning electron micrographs (SEM) of ePTFE showed preferential attachment to the nodes whilst on Gelseal, cells conformed to Dacron fibres at different levels and directions. Rapidly formed endothelial cell monolayers on ePTFE and Gelseal grafts resisted shear stress of flow with significant cell retention at 2 h. There was patchy coverage of both grafts with evidence of bridging of gaps between individual fibres in Gelseal.

Blood Vessel Prosthesis↗
PubMed1991

Adult human endothelial cell seeding using expanded polytetrafluoroethylene vascular grafts: a comparison of four substrates.

Prosthetic small-caliber vascular grafts give poorer patency rates than autogenous vein grafts, possibly because the former never spontaneously form endothelium. Animal studies have shown that endothelialization of prosthetic grafts can be encouraged by seeding endothelial cells into the graft at the time of surgery, resulting in improved patency. Information regarding the attachment characteristics of adult human endothelial cells to prosthetic grafts is, however, sparce. Laboratory experiments were performed by use of cell culture techniques to compare the attachment characteristics of adult human endothelial cells to expanded polytetrafluoroethylene graft material, both untreated and treated, with one of four protein substrates--preclotted blood, fibronectin, laminin, and type 4 collagen. Attachment characteristics were compared quantitatively by use of attachment assays and qualitatively by scanning electron microscopy. Attachment to untreated expanded polytetrafluoroethylene was poor but could be greatly improved by preclotting or precoating with any of the proteins, particularly fibronectin. In preclotted grafts seeded endothelial cells formed a virtually confluent monolayer after 1 hour. Cell attachment to the other grafts coated with protein was patchy and inconsistent. It is concluded that a rapid confluent endothelial lining within a prosthetic vascular graft is possible, and of the substrates examined, preclotted blood best encourages cell attachment to expanded polytetrafluoroethylene.

Blood Vessel Prosthesis↗
PubMed1990

Effects of shear stress on endothelial cell monolayers on expanded polytetrafluoroethylene (ePTFE) grafts using preclot and fibronectin matrices.

Animal studies have shown that endothelial seeding of vascular prosthetic grafts reduces thrombogenicity and improves their patency. However, for endothelial seeding to be of clinical benefit in humans, it must withstand shear stress of blood flow. Endothelial cells labelled with Indium-111-oxine were seeded in supra-confluent densities on preclot or fibronectin coated ePTFE graft segments over a period of 90 min. These grafts with rapidly formed endothelial cell monolayers were then exposed to varying shear stresses up to a flow rate of 300 ml/min, using tissue culture medium in an artificial flow circuit. Grafts coated with preclot matrix showed 2 h cell retentions of 82.4 +/- 6.8% at 25 ml/min, 79.9 +/- 8.2% at 100 ml/min, 75.4 +/- 9.5% at 200 ml/min and 58.3 +/- 15.5% at 300 ml/min whilst those for the fibronectin matrix were 57.8 +/- 9.9%, 55.2 +/- 13.3%, 55.4 +/- 12.9% and 56.5 +/- 15.2% respectively. Overall the preclot matrix was found to be better than fibronectin (P less than 0.001). Light and scanning electron microscopy revealed well-formed endothelial cell monolayers retained on preclot matrix up to a flow rate of 200 ml/min whereas uncovered patches were seen at 300 ml/min and at all flow rates on fibronectin matrix.

Blood Coagulation↗
PubMed1990

Fibronectin coating of expanded polytetrafluoroethylene (ePTFE) grafts and its role in endothelial seeding.

Although fibronectin's role as a matrix to improve endothelial seeding has been demonstrated by other workers, the optimum concentration for use has never been described. Attachment of fibronectin to expanded polytetrafluoroethylene (ePTFE) was measured, using 125I-radiolabeled protein, at different concentrations and for different time periods. The absolute amount of fibronectin bound to the graft increased with the concentrations used in coating (p less than 0.001) and also with time (p less than 0.01); e.g., at 50 micrograms/ml, 90 min of incubation produced a molecular attachment of 4.0 x 10(11)/cm2 of graft. However, its percentage attachment decreased with a rise in concentration (p less than 0.001). After an initial loss of 22% in 30 min, the fibronectin-graft bond was found to be stable when exposed to a shear stress produced by flow at 200 ml/min. No significant difference in the cell adherence could be found in grafts coated with fibronectin concentrations of 50, 150, and 250 micrograms/ml, although it was significantly less at 10 and 25 micrograms/ml (p less than 0.05).

Blood Vessel Prosthesis↗
PubMed1989

Cell seeding for small diameter ePTFE vascular grafts: a comparison between adult human endothelial and mesothelial cells.

A series of experiments was performed to compare the ability of adult human endothelial and mesothelial cells to attach and spread upon ePTFE graft material. Both cell types were harvested enzymatically and grown in culture. Two types of adhesion assay were used to assess the ability of the cultured cells to attach to ePTFE either uncoated or precoated with a variety of substrate proteins. The results showed that fibronectin, laminin, type 4 collagen and preclotted blood all greatly improve the attachment rate of endothelium to ePTFE. The extracellular matrix proteins, however, give patchy cell attachment, whereas cells seeded onto preclotted ePTFE form a virtually confluent monolayer after one hour's incubation. The matrix proteins similarly improve mesothelial attachment, although in all cases attached cells remain largely rounded up, with relatively few spreading on the surface. Mesothelial attachment to preclotted ePTFE is no better than attachment to the untreated material. It would seem that a preclotted graft seeded with endothelial cells is the combination most likely to result in a confluent monolayer within one hour.

Adult↗
PubMed1989

Lumboperitoneal shunt combined with myelotomy for treatment of syringohydromyelia.

This study was undertaken to investigate whether a direct communication between the fourth ventricle and the syrinx exists in the majority of patients with syringohydromelia and whether intraspinal pressure plays a role in the pathogenesis of this disorder. A series of 13 patients with syringohydromyelia delineated by magnetic resonance (MR) imaging was reviewed, and the intracranial pressure (ICP) and lumbar spinal pressure (LSP) were recorded concomitantly in three patients. Lumboperitoneal shunting was performed in seven patients, six of whom also underwent myelotomy of the caudal spinal cord. Magnetic resonance imaging visualized a cerebrospinal fluid (CSF) channel connecting the fourth ventricle with the syrinx in only one of the 13 patients, and in the remaining 12 patients it revealed a long segment of the spinal cord free of syrinx below the fourth ventricle. This finding is in accordance with recent MR studies of syringohydromyelia. The concomitant recording of ICP and LSP in our patients who had myelomeningocele and Chiari II malformation showed findings contradicting the reports of Williams. Lumbar spinal pressure was equal to ICP under steady-state conditions, and was elevated by straining or crying more markedly than ICP. Craniospinal pressure dissociation with ICP greater than with LSP, as described by Williams, was not observed. Lumboperitoneal shunting concomitant with myelotomy and syringopleural shunting 1 month after myelotomy resulted in marked and sustained shrinkage of the syrinx and neurological improvement in four patients. It was concluded that the majority of patients with syringohydromyelia and Chiari malformation lack a direct communication connecting the fourth ventricle with the syrinx. The results suggest that CSF moves under pressure into the spinal cord, contributing to the formation and maintenance of the syrinx, and that LP shunting combined with myelotomy can effect shrinkage of the syrinx.

Adolescent↗
PubMed1987

Subcutaneous calcium heparin versus intravenous sodium heparin in treatment of established acute deep vein thrombosis of the legs: a multicentre prospective randomised trial.

One hundred patients with phlebographically proved acute deep vein thrombosis of the legs were prospectively randomised into two treatment groups to compare the safety and efficacy of subcutaneous calcium heparin versus intravenous sodium heparin administered by constant infusion pump. The dose of heparin was determined by daily measurement of the kaolin cephalin clotting time. Treatment was maintained for up to 14 days, after which phlebography was repeated. Of 49 patients who received subcutaneous calcium heparin, two showed an increase in thrombus size, while eight showed complete lysis. In the 47 patients who received intravenous sodium heparin thrombus increased in size in 13 while only one showed evidence of complete lysis. These differences were significant. There were no significant differences between the two groups in the incidence of serious complications, although almost half of those receiving intravenous heparin had some minor problem with the constant infusion pump and just over half of those receiving subcutaneous heparin had some bruising at the injection site. This study showed that subcutaneous calcium heparin was more effective in helping lyse existing thrombus and preventing its propagation than intravenous sodium heparin.

Clinical Trials as Topic↗
PubMed1983

Dynamic preoperative assessment of cardiac reserve in elective aortic surgery.

Myocardial infarction accounts for over 50 per cent of mortality following elective abdominal aortic surgery. Previous history of ischaemic heart disease and abnormal ECGs, common in vascular patients, are unreliable parameters for predicting myocardial response to stress. Exercise ECGs are often valueless, as claudication may mask myocardial insufficiency. Myocardial performance was studied preoperatively in 29 consecutive patients undergoing elective aortic bifurcation grafting, using a Swann-Ganz catheter to measure the rise in pulmonary artery wedge pressure (PAWP) produced by rapid intravenous infusion of plasma (200-400 ml). A Frank-Starling Curve was obtained by plotting LVSWI against PAWP. Two important values were obtained: (a) 'Upslope' or gradient of the ascending portion of the curve. Low values identify patients most at risk from cardiac complications. Six patients who suffered from postoperative cardiac complications had a mean 'upslope' value of 1.568 +/- 0.681 (1 s.e.m.), whereas the 23 who did not, had a mean value of 7.094 +/- 0.745 (1 s.e.m.), a significant difference (P less than 0.001); (b) 'PAWPmax', the ventricular filling pressure above which work output dropped. Infusion beyond this may precipitate pulmonary oedema. PAWP was observed at levels greater than PAWPmax in all 6 patients who developed either pulmonary oedema or myocardial infarction. The myocardial performance curve can reliably identify high risk patients and permit control of intravenous therapy within individual safety limits, thereby preventing pulmonary oedema.

Adult↗
PubMed1976

Chronic evaluations of ventricular ejection phase dynamics during abdominal left ventricular assist device (ALVAD) pumping in the awake, unanesthetized calf.

In 1974, between 2 and 8% of the 50,000 adult patients undergoing cardiac surgery in this country succumbed in the early post-operative period from left ventricular failure, despite various methods of pharmacologic and/or mechanical support. Our laboratories have concentrated on the development, modification, evaluation, and validation of an abdominally positioned left ventricular assist device which has the potential of reducing these mortalities. Continuous testing in animals, for periods exceeding 2 mos, satisfied reliability, durability and longevity requirements. The cumulative results of these investigations were reviewed at the National Heart and Lung Institute on August 21, 1975. Authorization for clinical trials of the device according to specific criteria and protocols46 was approved on November 1, 1975. The ALVAD is now in the early stages of clinical testing. The results of the current experiments demonstrate that ventricular outflow impedance and prosthetic inflow impedance are the major determinants of left ventricular assist device hemodynamic effectiveness. By markedly reducing outflow impedance, the ALVAD profoundly lowers ventricular pressure-work and oxygen demands while simultaneously increasing ventricular performance and maintaining or augmenting systemic perfusion. Moreover, our studies indicate that improved device designs (intended for intermediate and long-term implantation) and maximal performance can be achieved by focusing on these central determinants.

Animals↗