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Biomedical subjects

P A Baskerville

Publications and source records attributed to P A Baskerville.

At least 19 recordsLinked to original sources
PubMed2001

L-arginine and S-nitrosoglutathione reduce embolization in humans.

BACKGROUND: L-Arginine reduces platelet aggregation and adhesion in ex vivo studies, but there is no evidence as yet that it has a therapeutic effect on clinical end points. Doppler ultrasound can detect cerebral emboli noninvasively. Such embolic signals are common after carotid endarterectomy, and their frequency predicts risk of stroke recurrence. We used this situation to determine the antiplatelet efficacy of L-arginine and S-nitrosoglutathione (GSNO), a physiological nitric oxide donor with possible platelet specificity. METHODS AND RESULTS: Patients undergoing carotid endarterectomy were randomized in a double-blind manner between L-arginine (n=14), GSNO (n=14), or placebo (n=14) administered intravenously for 90 minutes, starting 30 minutes after skin closure. All patients were pretreated with aspirin and given heparin during surgery. Transcranial Doppler recordings were made from the ipsilateral middle cerebral artery for 4 hours after surgery, beginning 30 minutes after skin closure, and also at 6 and 24 hours. There were highly significant reductions in the number of Doppler embolic signals in the L-arginine and GSNO groups; first 4 hours, median (range) number of embolic signals, placebo 44.7 (6 to 778), L-arginine 9.5 (0 to 225), and GSNO 0.8 (0 to 8), both P<0.001 versus control values. The reduction in the signals persisted at the 24-hour recording. CONCLUSIONS: Intravenous L-arginine and GSNO attenuate Doppler embolic signals in humans. Modulation of the NO system with these agents may have applications in the treatment of thromboembolic disease. This study demonstrates the potential application of ultrasonic embolic signal detection to examine the efficacy of new antiplatelet agents in relatively small numbers of patients.

Aged↗
PubMed1998

S-nitrosoglutathione reduces the rate of embolization in humans.

BACKGROUND: Antiplatelet agents presently used in the secondary prevention of cardiovascular disease fail to prevent the majority of cases of recurrent stroke and systemic embolization. An evaluation of the efficacy of new agents is hampered by a lack of in vivo models in humans. Asymptomatic cerebral embolic signals (ES) may be detected with the use of transcranial Doppler ultrasonography. These signals are particularly common after carotid endarterectomy, and this provides a situation in which new antiplatelet agents can be evaluated. With this model, we determined the effectiveness of S-nitrosoglutathione (GSNO), a nitric oxide donor with relative platelet specificity, in reducing cerebral embolization. METHODS AND RESULTS: Transcranial Doppler ultrasound recordings from the ipsilateral middle cerebral artery were made after carotid endarterectomy in 12 control patients and 12 patients receiving intravenous GSNO from the induction of anesthesia until 2 hours after skin closure. Recording times were 0.5 to 3.5, 6 to 7, and 24 to 25 hours after skin closure. The Doppler signal was recorded onto tape, and analysis for ES was performed, with the investigators blinded to treatment group. All patients received aspirin 300 mg/d before surgery and 5000 IU of heparin during surgery. The median (range) number of ES detected during the initial 3-hour postoperative recording was markedly reduced in the GSNO group compared with the control group: 7.5 (0 to 61) versus 38.5 (1 to 219) (P=0.018). This difference persisted until 6 hours after surgery. CONCLUSIONS: Despite the administration of aspirin and heparin, frequent embolization occurred and was markedly reduced after the administration of GSNO. This demonstrates the potential use of platelet-specific nitric oxide donors in the treatment of thromboembolic disease. This model of cerebral embolism may allow determination of the effectiveness of new antiplatelet agents in humans.

Aged↗
PubMed1998

Technical report: Combined carotid bifurcation endarterectomy and intra-operative transluminal angioplasty of a proximal common carotid artery stenosis: an alternative to extrathoracic bypass.

A method of management of a dual stenoses affecting the proximal common carotid artery and the internal carotid artery, the tandem lesion, is described in two cases. The combination of a surgical endarterectomy of the internal carotid artery narrowing and percutaneous balloon dilatation of the more proximal common carotid artery narrowing, via the arteriotomy site, with clamping of the internal carotid artery was successfully employed to avoid an extrathoracic bypass procedure.

Aged↗
PubMed1998

Undergraduate teaching in a day surgery unit: a 2-year evaluation.

Medical schools are having to adapt their teaching in response to the reduction in inpatient availability and the increase in outpatient and community care. A surgical course for first clinical-year undergraduate medical students was established in the day surgery unit at King's College School of Medicine and Dentistry in 1995. It was considered desirable because of the shift to day-case surgery, and proved feasible to run (Seabrook et al. 1997a). The course is taken by one-third of the annual intake of 120 students. A formal evaluation was undertaken comprising comparison of student performance in end-of-year clinical and multiple choice examinations and of acceptability to students, teachers and managers. The results showed no significant differences in performance between students who had taken the day-surgery course and those on other surgical attachments. Students' satisfaction with the course was significantly higher on nine individual criteria and lower on four criteria. The teaching was positively viewed by teachers and managers, despite having costs as well as benefits. We conclude that day-surgery centres can be used successfully to teach medical undergraduates. Experience in both inpatient and day-case environments should benefit students by reflecting more closely the reality of current surgical care.

Ambulatory Surgical Procedures↗
PubMed1997

Teaching and learning in day surgery units: a UK survey.

Recent increases in day case surgery offer new opportunities for medical student learning, whilst the reduction in surgical beds and length of hospital stays has reduced opportunities in traditional inpatient settings. To establish the extent and nature of undergraduate medical education in day surgery units in the UK, the authors undertook a postal questionnaire survey. Of the 227 units which replied, 45% are used for teaching. In 83% of these, students attend only single operating lists, and only 7% of units take students for more than 1 day per week. This suggests that students have very limited teaching in day surgery units. Diagnosis, common surgical procedures and rehabilitation are increasingly carried out in outpatient, day case and community settings. These may be missed by students unless educational programmes are responsive to trends in health care delivery. Day surgery units could play an increased role in medical education.

Ambulatory Surgical Procedures↗
PubMed1995

Basic fibroblast growth factor upregulates the expression of vascular endothelial growth factor in vascular smooth muscle cells. Synergistic interaction with hypoxia.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a hypoxia-inducible direct angiogenic factor. Upregulation of VEGF is thought to mediate many of the angiogenic effects of growth factors that are not direct endothelial cell mitogens. Like VEGF, basic fibroblast growth factor (bFGF) is considered to induce angiogenesis by a direct effect on endothelial cells. This study investigated the possibility that bFGF may also act indirectly by regulating VEGF expression in vascular smooth muscle cells (VSMCs). METHODS AND RESULTS: Incubation of confluent and quiescent cultures of rabbit VSMCs with bFGF caused a time- and concentration-dependent increase in steady-state levels of VEGF mRNA, as analyzed by Northern blot hybridization. Exposure of VSMCs to a threshold hypoxic stimulus (2.5% O2) caused a modest increase in VEGF mRNA levels. However, the combination of 2.5% O2 with bFGF had a marked synergistic effect. This effect was specific for VEGF as hypoxia did not enhance bFGF-induced expression of the proto-oncogene c-myc. Synergistic upregulation of VEGF mRNA expression also was observed between hypoxia and TGF-beta 1. CONCLUSIONS: These results suggest that bFGF may promote angiogenesis both by a direct effect on endothelial cells and also indirectly by the upregulation of VEGF in VSMCs. The synergy demonstrated between hypoxia and either bFGF or TGF-beta 1 suggests that multiple diverse stimuli may interact via the upregulation of VEGF expression in VSMCs to amplify the angiogenic response.

Animals↗
PubMed1995

Hypoxia and platelet-derived growth factor-BB synergistically upregulate the expression of vascular endothelial growth factor in vascular smooth muscle cells.

Vascular endothelial growth factor (VEGF) mRNA expression was analysed in rabbit vascular smooth muscle cells following exposure to hypoxia and platelet-derived growth factor-BB (PDGF-BB). Hypoxia potently upregulated VEGF mRNA steady-state levels in a time- and concentration-dependent manner reaching a maximum level (approximately 30-fold increase) after 12-24 h at 0% 0(2). In contrast, PDGF-BB caused a modest increase in VEGF expression. However, the combination of PDGF-BB and a threshold hypoxic stimulus (2.5% O2 for 4 h) had a marked synergistic effect. Synergy between hypoxia and PDGF-BB was selective for VEGF expression as hypoxia had no effect on the PDGF-induced upregulation of the proto-oncogene c-myc. These results raise the possibility that hypoxia and PDGF-BB may act in concert to induce VEGF expression in the arterial wall during the development of atherosclerosis.

Base Sequence↗
PubMed1995

The influence of the adventitia on the presence of smooth muscle cells and macrophages in the arterial intima.

OBJECTIVE: To test the hypothesis that atherosclerosis may be initiated by hypoperfusion or thrombotic occlusion of the adventitial vasa vasonum. DESIGN: In a new model of atherogenesis, an early atherosclerotic lesion may be initiated by removal of the adventitia from the carotid artery of the New Zealand White rabbit, wherein lie the vasa vasorum. SETTING: Animal laboratory, University Department of Surgery and Medicine. CHIEF OUTCOME MEASURES: Immunocytochemistry was undertaken to demonstrate the presence of smooth muscle cells and macrophages within the intimal lesions. Smooth muscle cells were labelled with a monoclonal antibody designated HHF35 and macrophages were labelled with a rabbit specific, macrophage specific antibody, RAM11. CHIEF RESULTS: In rabbits fed a normal diet, at day 14, the intimal lesion was composed exclusively of smooth muscle cells. By day 28, such lesions had regressed. In rabbits fed a high cholesterol diet, at day 14, the intimal lesion was composed of a mixture of macrophages and smooth muscle cells. By day 42, the pattern of cellular distribution was such that macrophages (present as foam cells) were predominant. In the presence of persistent hypercholesterolaemia these lesions did not regress. CONCLUSIONS: This new model can produce two different cellular responses that may mimic the intimal lesions seen with re-stenosis after angioplasty or in hypercholesterolaemic man and as such, might be useful in separating out these two different pathophysiologies.

Animals↗
PubMed1995

Response of digital arteries to endothelium dependent and independent vasodilators in patients with Raynaud's phenomenon.

The cause of the digital artery spasm seen in Raynaud's phenomenon (RP) is unclear. A dysfunction of endothelium-dependent vasodilation might contribute to the development of this spasm. We studied the digital artery responses to endothelium-dependent and independent vasodilators in eight Raynaud's phenomenon patients and eight sex-matched controls. A sequential series of infusions alternating with physiological saline were administered at a rate of 1 mL min-1 via the radial artery. The infusions contained acetylcholine chloride (ACh) 110 nm mL-1 and 550 nm mL-1, L-arginine 50 mumol mL-1, prostacyclin (PGI2) 2.5 ng mL-1 and glyceryl trinitrate (GTN) 4.5 nm mL-1. Digital artery diameter (DAD) and cutaneous temperature were measured. DAD was measured using a high frequency A-mode ultrasound scanner. There was no significant difference in mean brachial artery pressure, digital cutaneous temperature and DAD between the two groups at the start of the study. Comparing responses in the groups, there was a significantly greater increase in DAD and cutaneous temperature to Ach (endothelium-dependent vasodilator) at both concentrations in controls. A significantly greater increase in DAD was obtained in response to GTN (endothelium-independent vasodilator) in the RP subjects. There was no significant difference in response to L-arginine and PGI2 between the groups. These results suggest that a dysfunction of endothelium-dependent vasodilation is present in RP patients.

Acetylcholine↗
PubMed1995

False aneurysm of the carotid artery.

Vascular injury following penetrating neck trauma may be present despite a lack of clinical signs. Management of wounds deep to platysma should include a high level of suspicion and thorough investigation to exclude these 'silent' vascular injuries. This may prevent serious late complications.

Adult↗
PubMed1994

The adventitia and atherogenesis: removal initiates intimal proliferation in the rabbit which regresses on generation of a 'neoadventitia'.

Removal of the carotid artery adventitia from rabbits induced the formation of an intimal hyperplastic lesion. In rabbits fed a normal diet, the lesion (measured as the intimal:medial ratio) was maximal by day 14 (0.456 +/- 0.079, n = 5, P < 0.01) and thereafter, regressed towards control dimensions (0.037 +/- 0.003, n = 14) by day 28 (0.080 +/- 0.025, n = 7, P = 0.14). In rabbits fed a high cholesterol diet, the lesion was again maximal by day 14 (0.376 +/- 0.056, n = 8, P < 0.01). Although some regression was seen, the lesion persisted to day 42 (0.272 +/- 0.052, n = 8, P < 0.01). Electron microscopy and immunocytochemistry showed two types of lesion, (a) smooth muscle cell predominant on normal diet and, (b) macrophage predominant on high cholesterol diet. Smooth muscle cell predominant lesions underwent almost complete regression, whereas macrophage predominant lesions persisted. We propose that lesion formation may be initiated following the development of arterial wall hypoxia, secondary to excision of the adventitial vasa vasorum. Furthermore, we have devised a novel method to restore a highly vascular 'neoadventitia' to an artery whose adventitia has previously been removed, using loosely placed PVC tubing. We suggest this 'neoadventitia' was able to inhibit the formation of an intimal hyperplastic lesion and to promote regression of an already established lesion by restoring arterial wall oxygenation.

Animals↗
PubMed1994

Raynaud's phenomenon and cold stress testing: a new approach.

There are a number of methods of evaluating digital blood flow in the vascular laboratory but none fulfills the criteria of providing a quick and reproducible diagnostic test for Raynaud's phenomenon. We present our experience with the use of high frequency ultrasound to provide direct real time imaging of the digital arteries. Using this method and a standardised cold challenge test, consisting of exposure of the hand to a temperature of 10 degrees C for 5 minutes, it is possible to distinguish patients with Raynaud's phenomenon from normal controls on the basis of extent of digital artery closure. The mean fall in digital artery diameter on cold challenge, expressed as a percentage of the original diameter, was 92.4% (S.D. = 16.4, S.E.M. = 2.1) in patients with Raynaud's phenomenon as against 8.7% (S.D. = 11.5, S.E.M. = 2.5) in a group of normal volunteers. Using a 45% fall in digital artery diameter as the diagnostic cut-off point, the test has a specificity of 100% and a sensitivity of 96.6% in differentiating patients with Raynaud's phenomenon from controls. It is suggested that the test could be used as objective confirmation of a clinical diagnosis and to assess the efficacy of therapeutic interventions.

Adolescent↗
PubMed1993

Arterial intimal hyperplasia after occlusion of the adventitial vasa vasorum in the pig.

Oxygenation of the arterial wall is provided by diffusion of oxygen outward from the main vessel lumen and inward from the adventitial vasa vasorum. In a group of four Yucatan miniature pigs the oxygenation profiles across the superficial femoral arteries were recorded by polarographic oxygen microelectrodes. The profiles obtained suggested a relatively poorly oxygenated media (a trough value of approximately 25% that of the intimal oxygenation) with a progressive rise in oxygenation toward the intimal and adventitial surfaces. In four other survival experiments, occlusion of the adventitial vasa vasorum by flush ligation of the arterial branches that supply them resulted in the production of a focal, intimal hyperplastic lesion that was absent in control vessels (intimal to medial ratios [mean +/- SEM] of 0.053 +/- 0.008, n = 8, p < 0.001 and 0.013 +/- 0.001, n = 8, respectively). By electron microscopy this lesion was seen to be composed mainly of smooth muscle cells. This evidence would support the hypothesis that arterial wall hypoxia may be involved in the initiation of intimal hyperplasia. It is proposed that human atherosclerosis may be initiated by occlusion of the vasa vasorum and concomitant hypoxia.

Animals↗
PubMed1992

The vasa vasorum of the rabbit carotid artery.

The anatomy of the vasa vasorum of the carotid arteries was assessed by light and electron microscopy in a series of 25 New Zealand White male rabbits. The low viscosity acrylic resin, LR White, was used to cast the microvasculature. The carotid artery was found to have an endothelial monolayer placed directly upon a broad fenestrated internal elastic lamina. The media consisted of 12-18 laminae comprised of smooth muscle cells, elastin, collagen and ground substance. Vasa vasorum were confined to the adventitial layer, with no penetration into the media. They arose directly from the lumen of the carotid artery in addition to the arterial branching points. The potential role of the vasa vasorum in the aetiology of atherosclerotic plaques is discussed.

Animals↗
PubMed1991

Digital artery calibre measurement--a new technique of assessing Raynaud's phenomenon.

This study evaluated the use of a high frequency A-mode ultrasound scanner (CUTECH DM70) for monitoring the digital artery vasospasm of Raynaud's Phenomenon (RP). The technique was evaluated on 12 RP patients and 12 age and sex matched controls. The diameter of a single digital artery was measured in these subjects over a range of finger temperatures between 14-35 degrees C. The reproducibility of the measurements was assessed by repeating the procedure in two subjects (a control and an RP patient) on 5 separate days. The results confirmed that the technique is reproducible and monitored vasospasm occurring in all 12 RP patients. In the temperature range tested, none of the controls developed digital artery vasospasm. At finger temperatures greater than 25 degrees C the response to thermal stimuli of the digital arteries in RP patients and controls was similar. However, at temperatures less than 25 degrees C a marked vasoconstriction leading to complete digital artery closure was seen in the RP patients and not in the controls. This technique may prove useful in monitoring RP patients.

Adult↗
PubMed1991

Falsely raised ankle/brachial pressure index: a method to determine tibial artery compressibility.

The ankle/brachial index (abPI) may be falsely raised, notably in diabetes, due to the relative incompressibility of the tibial artery. This paper presents a method of determining tibial artery compressibility by deriving abPIs with the patient supine and with legs raised in increments up to 0.55 m (ankle to heart). The effective negative hydrostatic pressure superimposed on the blood pressure at the ankle was converted to mmHg, normalised with respect to the brachial systolic pressure and then expressed as a hydrostatic pressure index (hPI). abPI was regressed on hPI and the gradient of the regression line calculated. If the arterial wall offers no significant resistance to compression the measured pressure will equal intraluminal pressure. In this case regression of the changing arterial pressure with the applied hydrostatic pressure would be expected to produce a gradient of -1. With resistance to compression the measured pressure is greater than the intraluminal pressure and a steeper gradient would be expected. The method was tested using age and sex matched groups, (A) controls (16 arteries), (B) patients with PVD and no diabetes (17 arteries), and (C) diabetics with PVD (34 arteries). There was no significant difference between the regression line gradients of groups A and B but both differ significantly from group C. The difference between the medians of groups B and C was 0.46, the 95% confidence interval for the difference being 0.66 to 0.02. Twelve of the diabetic arteries had a gradient steeper than -1.8 compared with one from group (B) and none from group (C).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Ultrasound imaging of digital arteries.

This study assessed the use of high frequency ultrasound (CUTECH DM70) in the measurement of digital artery diameters. The accuracy of the technique was assessed using a model. Four silicone tubes of different diameters were embedded in opaque agar. Three independent observers measured the diameter of the tubes using the CUTECH DM70 and the measurements obtained were compared with those obtained using a travelling light microscope. The technique was then evaluated on digital arteries. Ten recordings of digital artery diameter were made at a fixed point on the index finger in two subjects at 20 degrees C and at 30 degrees C. There was no statistical difference between the mean diameters obtained by the three observers using the CUTECH DM70 on the model. No statistical difference was noted when the mean diameters measured using the travelling microscope were compared with those obtained by the three observers. The diameter differences between the tubes were all highly significant (P less than 0.001 Mann Witney). The variability in the recordings of digital artery diameter in the two subjects was very low (maximum coefficient of variance less than 4%). A significant difference in the mean measured vessel diameter at the two different temperatures was obtained (P less than 0.001 Mann Witney). We conclude that digital artery diameter can be measured using the CUTECH DM70.

Arteries↗