Biomedical subjects

M G Walker

Publications and source records attributed to M G Walker.

At least 37 records · Page 2Linked to original sources

PubMed1996

Endothelial cell seeding kinetics under chronic flow in prosthetic grafts.

Improved patency of endothelial cell seeded grafts relies on good initial adherence and cell retention when the circulation is restored. In this study human adult endothelial cells (HAECs) were used to evaluate the suitability of commercially available prostheses for seeding. Acutely seeded indium-111 oxine labeled HAECs were used to measure cell adherence to plain and fibronectin (FN)-coated expanded polytetrafluoroethylene (ePTFE), gelatin-impregnated Dacron (Gelseal), and collagen-impregnated Dacron (Hemashield) grafts. Cell loss from FN-coated prostheses, when exposed to a simulated human arterial blood flow of 200 ml/min in an artificial pulsatile circulation, was quantified from the loss of gamma activity from the graft over 24 hours, pressure in the circulation being reduced to 15 mm Hg to reduce fluid loss. Initial HAEC adherence (mean [SD]) to plain grafts was 3(1)%, 47(9)%, and 53(9)% for ePTFE, Gelseal, and Hemashield, respectively. This improved significantly with FN coating (78[6]%, 60[8]%, and 76[4]%). Cell retention after 24 hours of flow to FN-coated grafts was 16(10)%, 25(5)%, and 65(4)% and was confirmed qualitatively by scanning electron microscopy and environmental scanning electron microscopy. FN significantly improved initial cell adherence with Dacron grafts showing the better adherence. Cell retention after 24 hours of flow was better with FN-coated Dacron than with ePTFE but was best with Hemashield grafts.

Adult↗

PubMed1996

Dialysis fluid cytotoxicity and inhibition of host defence in cultured human mesothelial cells are neutralized rapidly with incubation in the peritoneum.

BACKGROUND: A recent survey puts the global dialysis population at 535100; of those on peritoneal dialysis, 85% are on continuous ambulatory peritoneal dialysis. Current hyperosmolar dialysis fluids are toxic to peritoneal cells and inhibit certain host-defence functions. An alternative preparation, glucose polymer, has recently been developed. METHODS: Mesothelial cell viability, interleukin-6 and prostacyclin synthesis, after exposure to 7.5% glucose polymer, 1.36% glucose or 3.86% glucose peritoneal dialysis effluent solution was assessed. RESULTS: In its neat form, at an original pH of 5.4, glucose polymer was as toxic as hyperosmolar solutions (P < 0.01). Synthesis of interleukin-6 and prostacyclin were significantly inhibited by neat dialysis fluid, (P < 0.01). However, after an in vivo intraperitoneal incubation of only 15 min the toxicity of all solutions tested in vitro was lost. CONCLUSIONS: Despite rapid in situ neutralization of dialysis fluid toxicity, mesothelial injury and inhibition of host-defence function, early in the dialysis cycle, may affect peritoneal physiology given the complex network of pathways to which these cells contribute. Although recent trials indicate improved ultrafiltration is achievable with glucose polymer, it is not a biocompatible dialysis fluid in its current manufactured form.

6-Ketoprostaglandin F1 alpha↗

PubMed1995

Indium-111 platelet scintigraphy in vascular disease.

Indium-111 labelled platelet scintigraphy permits simple, accurate evaluation of platelet kinetics and sites of deposition. The most meaningful results are obtained from serial scans, although these are clinically useful in only a few of the many applications that have been suggested, principally in studies of acute thrombosis, prosthetic graft thrombogenicity and antiplatelet medication. Key pitfalls are associated with selection of regions and patient variation.

Arteriosclerosis↗

PubMed1995

Restoring lower limb blood flow improves conduction velocity in diabetic patients.

Human diabetic peripheral neuropathy is believed to have, at least in part, a microvascular basis. This study was designed to examine the effects of restoration of arterial blood supply on peripheral nerve function in six non-insulin-dependent diabetic patients with peripheral occlusive vascular disease. In the revascularised legs, transcutaneous oxygen increased from a median 37.5 (28.5-45.7 interquartile range) mmHg to 55.5 (53.5-62.5) mmHg, p = 0.036, mean increase 20.2 (14.8-25.6, 95% confidence intervals(CI) mmHg. This was accompanied by a significant improvement in peroneal motor nerve conduction velocity from 31.7 (26.5-36.3) m/s to 33.5 (32.9-39.4) m/s, p = 0.04, mean increase 4.7 (1.7-7.7, 95% CI) m/s. There was no significant change in transcutaneous oxygen or peroneal nerve motor conduction velocity in the contralateral control limbs. This improvement in conduction velocity with improved tissue oxygenation suggests that studies of agents which might indirectly bring about improvements in microvascular blood flow should be urgently considered.

Aged↗

PubMed1995

Fibrinolysis profiles and platelet activation after endothelial cell seeding of prosthetic vascular grafts.

There is no convincing evidence that endothelial cell seeding of prosthetic grafts in humans confers any of the advantages seen in animals. However, partial endothelial coverage might exert a subtle effect not detectable with indirect end points such as patency or scintigraphy. This study examined seeded cell function by measuring fibrinolytic and platelet activation markers in patients receiving seeded and control prosthetic grafts. Thirty-two patients were randomly assigned to seeded (n = 15) and control (n = 17) groups. Preoperatively and 3, 6, and 12 months postoperatively, plasma levels of fibrinopeptide A (FPA), B beta 1-42 fragment, cross-linked fibrin degradation products (XL-FDP), thromboxane A2 (TXA2), platelet factor 4 (PF4), and beta-thromboglobulin (beta TG) were measured. Patients with seeded grafts had significantly lower levels of FPA at 6 and 12 months (p < 0.05) and a significant overall group effect (p < 0.05). These patients also tended to have higher levels of XL-FDP (p < 0.1). No other significant differences were seen. The lower rate of conversion of fibrinogen to fibrin and the trend toward increased fibrinolysis seen in seeded grafts may be due to the metabolic effects of viable retained seeded cells. Although comparable platelet activation indicates that endothelial coverage remains limited, seeding may exert an antithrombotic influence at the graft surface.

Adult↗

PubMed1995

Evaluation of dopexamine hydrochloride as a renoprotective agent during aortic surgery.

Thirty-two patients undergoing elective infrarenal aortic surgery were randomly assigned to receive a perioperative infusion of either dopexamine hydrochloride at a rate of 2 micrograms/kg/min (n = 15) or 0.9% saline solution as placebo (n = 17). Renal function was monitored by regular measurements of serum creatinine levels. There were significant mean percentage increases in serum creatinine (p < 0.001) at all time points up to 3 days postoperatively in the placebo group but only at 2 and 12 hours in the dopexamine group. It was concluded that dopexamine hydrochloride confers renal protection in patients undergoing aortic reconstruction.

Aortic Aneurysm, Abdominal↗

PubMed1995

Ruptured infected popliteal artery aneurysm.

We describe an unusual presentation of an infected popliteal aneurysm. To our knowledge rupture of an aneurysm associated with Salmonella at this site has not previously been reported. The management of infected aneurysms is discussed.

Aged↗

PubMed1995

Culture of human adult endothelial cells on endarterectomy surfaces.

OBJECTIVES: Endothelial cell seeding of prosthetic grafts has not been as successful as initially hoped and the application of seeding technology to alternative reconstructive procedures such as endarterectomy and angioplasty has been increasingly considered. The success of such seeding depends on the ability of the seeded cells to attach to, and form a monolayer on the endarterectomised vessel wall which was the aim of this study. METHODS: Using a seeding chamber model, heterologous human adult endothelial cells were seeded onto fresh human endarterectomy specimens and cultured. Studies of endothelial call adherence to endarterectomy specimens were performed using 111-Indium oxine labelled cells using methodology analogous to graft seeding. RESULTS: Mean endothelial cell adherence of 70% (S.D. 10%) after 1 h incubation was achieved and the successful development of a monolayer of human adult venous endothelial cells on endarterectomised arteries was demonstrated in vitro. CONCLUSIONS: These results indicate that closed endarterectomy appears to offer a surface with cell attachment that is superior to prosthetic grafts. Where femoral endarterectomy is appropriate, endothelial seeding potentially offers a method of reducing thrombogenicity and intimal hyperplasia, improving patency and avoiding a prosthetic graft whilst preserving collateral circulation and autologous vein.

Adult↗

PubMed1995

Systemic endotoxaemia and fibrinolysis during aortic surgery.

OBJECTIVE: To determine whether endotoxaemia and activation of the systemic fibrinolytic system occurs during and after aortic surgery. DESIGN: Prospective clinical study. SETTING: University Hospital. MATERIALS: 31 patients undergoing aortic surgery. CHIEF OUTCOME MEASURES: Venous blood assay for endotoxin and plasminogen activator inhibitor-1 (PAI-1). Samples were obtained preoperatively, immediately before and 5 minutes after cross-clamp application and removal, and at 2, 4, 6 and 24 hours postoperatively. Tonometric sigmoid intramural pH was monitored throughout this period as a means of detecting colonic mucosal ischaemia. MAIN RESULTS: Endotoxin levels increased after clamping of the aorta, peaking immediately before clamp removal, mean value 34.5 pg/ml, p < 0.01, but returning to preoperative levels by 24 hours. PAI-1 levels progressively increased after surgery, with persistently high levels remaining at 24 hours (p < 0.01). CONCLUSIONS: Endotoxaemia does occur during aortic surgery and appears to be associated with activation of the systemic fibrinolytic system.

Acidosis↗

PubMed1995

Hierarchical neural networks for survival analysis.

Neural networks offer the potential of providing more accurate predictions of survival time than do traditional methods. Their use in medical applications has, however, been limited, especially when some data is censored or the frequency of events is low. To reduce the effect of these problems, we have developed a hierarchical architecture of neural networks that predicts survival in a stepwise manner. Predictions are made for the first time interval, then for the second, and so on. The system produces a survival estimate for patients at each interval, given relevant covariates, and is able to handle continuous and discrete variables, as well as censored data. We compared the hierarchical system of neural networks with a nonhierarchical system for a data set of 428 AIDS patients. The hierarchical model predicted survival more accurately than did the nonhierarchical (although both had low sensitivity). The hierarchical model could also learn the same patterns in less than half the time required by the nonhierarchical model. These results suggest that the use of hierarchical systems is advantageous when censored data is present, the number of events is small, and time-dependent variables are necessary.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Influence of renal artery blood flow on renal function during aortic surgery.

BACKGROUND: This study was undertaken to determine the true incidence of renal impairment after aortic surgery and its association with intraoperative fluctuations in renal artery blood flow and cardiac output. METHODS: Direct measurements of renal artery blood flow were undertaken with electromagnetic flowmetry in 19 patients undergoing elective infrarenal aortic surgery. Renal function was assessed before and after operation by measurement of creatinine clearance. RESULTS: Twelve patients (63%) had renal impairment as defined by a 40% or greater reduction in creatinine clearance after operation. This group of patients had significantly lower renal artery blood flow during the period of aortic cross-clamping than had those who preserved their renal function (p < 0.001). CONCLUSIONS: Renal impairment is common after infrarenal aortic surgery and may be a result of intraoperative ischemia secondary to reduced renal artery blood flow.

Adult↗

PubMed1993

Acute ischaemia of the lower limb: an unusual presenting feature of acute lymphoblastic leukaemia.

Malignant disease is often complicated by coagulation disorders presenting as abnormal clotting or bleeding, acute leukaemia being more often associated with the latter. Acute lymphoblastic leukaemia presenting with peripheral arterial thromboembolism, previously unreported in the literature, is presented. Aetiology, clinical features, and management of coagulation disturbances associated with malignancy are also reviewed.

Adult↗

PubMed1993

The preservation of renal function by isovolemic hemodilution during aortic operations.

PURPOSE: In an investigation of the effects of isovolemic hemodilution, 39 consecutive patients undergoing elective infrarenal aortic operation had detailed measurements of renal function, renal artery blood flow, and cardiac hemodynamics. METHODS: The patients were randomly allocated to receive acute preoperative isovolemic hemodilution to a hematocrit of 28%, with 20 patients receiving hemodilution and 19 being control subjects. RESULTS: Twelve (63%) of the control group had renal impairment, compared with only four (20% in the group receiving hemodilution (p < 0.01). Hemodilution also prevented the fall in cardiac output induced by cross-clamping (p < 0.01) and significantly reduced the need for transfusion of donor blood (p < 0.01). CONCLUSIONS: Acute isovolemic hemodilution is clearly a useful adjunct in the management of patients undergoing elective aortic operation.

Acute Kidney Injury↗

PubMed1992

Role of topical lignocaine during carotid endarterectomy.

Forty carotid endarterectomies were undertaken in 34 patients. Operations were prospectively randomized to periarterial application of either 1 per cent lignocaine (n = 19) or normal saline (n = 21), and detailed measurements taken of intraoperative pulse rate and blood pressure. Patients receiving lignocaine demonstrated a lower pulse rate, and lower systolic and mean blood pressures than those receiving placebo, with significance in relation to clamp application and shunt removal (P < 0.05). It was particularly noticeable that patients receiving lignocaine demonstrated less intraoperative variation in pulse rate and blood pressure. Topical lignocaine stabilizes pulse rate and blood pressure during carotid endarterectomy.

Administration, Topical↗

PubMed1992

Correlations between nerve function and tissue oxygenation in diabetic patients: further clues to the aetiology of diabetic neuropathy?

Transcutaneous oxygen, laser Doppler flowmetry, peroneal nerve motor conduction velocity and skin temperature were assessed in both legs of 34 diabetic patients, who had a mean age of 41 (range 29-77) years, and diabetes duration of 21 (3-34) years. Transcutaneous oxygen significantly correlated with peroneal nerve motor conduction velocity (r = 0.59 p < 0.001) and laser Doppler flowmetry (r = 0.7 p < 0.001). Laser Doppler flowmetry correlated weakly with peroneal motor conduction velocity, (r = 0.34 p < 0.05). In each patient the leg with the higher transcutaneous oxygen (mean 70.2 +/- 9.3 (SD) mmHg) had a significantly higher peroneal motor conduction velocity (45.3 +/- 7.1 vs 41.5 +/- 6.3 m/s, p < 0.01), than the leg with the lower transcutaneous oxygen (61.0 +/- 11.9 mmHg), though no difference in skin temperature was observed, 31.4 +/- 0.4 vs 31.1 +/- 0.5 degrees C. We then assessed the potential for reversibility of conduction velocity deficits in ten non-diabetic patients, aged 59 (52-77) years, undergoing unilateral femoro-popliteal bypass, measuring transcutaneous oxygen, peroneal nerve motor conduction velocity and skin temperature pre- and 6 weeks post-surgery. In the control leg (unoperated) there was no significant change in transcutaneous oxygen (63.2 +/- 8.8 vs 63.0 +/- 4.6 mm Hg), peroneal nerve motor conduction velocity (45.1 +/- 7.8 vs 43.4 +/- 7.2 m/s) or skin temperature (30.8 +/- 1.3 vs 30.2 +/- 1.2 degrees C) after surgery (all NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Endothelial cell seeding: a review.

The concept of endothelial cell seeding, designed to provide vascular grafts with a nonthrombogenic lining, has progressed from crude animal experiments during the past two decades to detailed in vitro functional studies using human cells. Although favorable results have been obtained in animal studies this has yet to be translated to humans, where current application of these techniques has been limited to a very few clinical trials. The history, current status and future directions are reviewed herein.

Animals↗

PubMed1992

Fibronectin binding to gelatin-impregnated Dacron (Gelseal) prostheses.

Endothelial cell adherence to uncoated gelatin-impregnated Dacron (Gelseal) is poor but can be significantly improved by precoating with a suitable basement membrane such as fibronectin. To assess the suitability of fibronectin-coated Gelseal for endothelial cell seeding, fibronectin binding to Gelseal and its dissociation kinetics were investigated. Fibronectin binding was quantified by radiolabeling human fibronectin with iodine 125, concentrations of 10, 25, 50, 150, and 250 micrograms/ml being used to coat Gelseal at 30, 60, and 90 min of incubation. The amount of fibronectin bound was directly proportional to the concentration used and increased with time of incubation (p < 0.05). However, the percentage attachment decreased with increasing concentration (p < 0.001). The number of molecules bound per centimeter squared of graft was calculated. In the first 30 min, 75% of bound fibronectin was lost after exposure to a flow rate of 200 ml/min in a pulsatile artificial circulation; thereafter, the fibronectin-Gelseal bond was stable for up to 2 h.

Blood Vessel Prosthesis↗

PubMed1992

Probability estimation for biomedical classification problems.

Suppose that we wish to know the probability that an object belongs to a class. For example, we may wish to estimate the probability that a patient has a particular disease, given a set of symptoms, or we may wish to know the probability that a novel peptide binds to a receptor, given the peptide's amino-acid composition. The conventional approach is to first use a classification algorithm to find partitions in feature space and to assign each partition to a class, and then to estimate the conditional probabilities as the proportion of patients or peptides that are correctly and incorrectly classified in each partition. Unfortunately, this estimation method often gives probability estimates that are in error by 20% or more, and thus can cause incorrect decisions. We have implemented and compared alternative methods. In Monte Carlo simulations the alternative methods are substantially more accurate than is the current method.

Epidemiology↗