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Biomedical subjects

P D Hayes

Publications and source records attributed to P D Hayes.

At least 19 recordsLinked to original sources
PubMed2006

Cerebral protection during open retrograde angioplasty/stenting of common carotid and innominate artery stenoses.

BACKGROUND: This was a retrospective study of the effectiveness of open, retrograde angioplasty/stenting of supra-aortic arterial stenoses combined with transcranial Doppler-directed dextran therapy in preventing perioperative embolization. METHODS: Eight patients underwent angioplasty/stenting of the proximal common carotid (synchronous carotid endarterectomy (CEA) in six), while four underwent angioplasty/stenting of the innominate artery (synchronous CEA in one). Open exposure of the carotid bifurcation enabled temporary carotid clamping to protect the brain from procedural embolization. Dextran was administered to patients with a high rate of embolization on transcranial Doppler after the operation. RESULTS: No emboli were recorded in the cerebral circulation during the actual angioplasty procedure when the internal carotid artery was clamped. After operation three patients developed high-rate embolization and received dextran. No strokes or deaths occurred within 30 days of treatment. One patient developed symptoms and a recurrent stenosis greater than 50 per cent during follow-up and was treated by redo angioplasty. CONCLUSION: Retrograde angioplasty/stenting with or without synchronous CEA offers an alternative approach to treating patients with supra-aortic inflow disease.

Adult↗
PubMed2004

An in vitro model to compare the antimicrobial activity of silver-coated versus rifampicin-soaked vascular grafts.

In situ replacement of infected vascular grafts is an accepted alternative to total graft excision and extraanatomic replacement. Its success relies upon the ability of the newly inserted graft to resist recurrent infection. This study compares the efficacy of two methods used to reduce the risk of graft reinfection: rifampicin soaking versus silver bonding of grafts. The grafts' resistance to infection was tested in vitro in two protocols, each using a panel of seven common bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). The length of time the grafts remained free of organisms was compared between the groups. Both the silver graft and the rifampicin-soaked graft were significantly better than control graft at preventing bacterial growth on the graft surface. The rifampicin inhibited the growth of the gram-positive organisms, including MRSA, significantly better than the silver graft on days 2 and 3 (p < 0.001). Conversely, the silver graft was significantly more effective against the gram-negative organisms until day 4 (p < 0.0001). Both types of graft inhibit the in vitro growth of bacteria more effectively than controls, with rifampicin being most effective against gram-positive organisms and silver being best against the gram-negative organisms.

Acetates↗
PubMed2004

Subintimal angioplasty in lower limb ischaemia.

Subintimal angioplasty has been suggested as a treatment option for occlusive disease and has become an established practice in some centres, reducing their operative workload considerably. Others have concerns about the safety and durability of the procedure. This review will focus on the evidence for the use of subintimal angioplasty in lower limb occlusive disease. A systematic review of the literature from a Medline search has been carried out. Despite a paucity of trial data, subintimal angioplasty is now an established technique for the treatment of lower limb occlusive disease. The results for femoro-popliteal disease are well documented, with excellent technical and clinical success rates and low complication rates. The results for iliac disease are less well documented and demand caution. For infra-popliteal disease with critical ischaemia, the technique is again safe with good short and long-term results in a group of patients in whom distal bypass surgery is often risky. Subintimal angioplasty has a definite learning curve and those wishing to take it up should visit an experienced centre first. To achieve widespread acceptance it is likely to require large scale randomised controlled trials.

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PubMed2003

The excess of strokes in female patients after CEA is due to their increased thromboembolic potential--analysis of 775 cases.

INTRODUCTION: Women suffer an excess of complications following arterial surgery, including an increased stroke risk following CEA. In order to investigate this further we studied men and women's thromboembolic potential following CEA. METHOD: Analysis of prospectively collected data on 775 consecutive CEAs performed between October 1995 and October 2001, to identify the number of microembolic events detected following CEA. RESULTS: Overall women had a 2.2 fold increase in the number of postoperative emboli detected (95% CI 1.2-3.3). Of those patients with significant numbers of postoperative emboli (>25), 68% were female against 22% for men (p=0.009). In order to prevent progression onto postoperative thrombotic stroke 9.7% of women were treated with intravenous Dextran-40 therapy, as opposed to only 2.7% of men (p=0.013). There were no significant differences between men and women's preoperative risk factors and/or factors relating to their operation. CONCLUSION: It is possible that women's excess of postoperative complications following arterial surgery is related to their apparent increased thromboembolic potential following acute arterial injury.

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PubMed2002

TRPV3 is a temperature-sensitive vanilloid receptor-like protein.

Vanilloid receptor-1 (VR1, also known as TRPV1) is a thermosensitive, nonselective cation channel that is expressed by capsaicin-sensitive sensory afferents and is activated by noxious heat, acidic pH and the alkaloid irritant capsaicin. Although VR1 gene disruption results in a loss of capsaicin responses, it has minimal effects on thermal nociception. This and other experiments--such as those showing the existence of capsaicin-insensitive heat sensors in sensory neurons--suggest the existence of thermosensitive receptors distinct from VR1. Here we identify a member of the vanilloid receptor/TRP gene family, vanilloid receptor-like protein 3 (VRL3, also known as TRPV3), which is heat-sensitive but capsaicin-insensitive. VRL3 is coded for by a 2,370-base-pair open reading frame, transcribed from a gene adjacent to VR1, and is structurally homologous to VR1. VRL3 responds to noxious heat with a threshold of about 39 degrees C and is co-expressed in dorsal root ganglion neurons with VR1. Furthermore, when heterologously expressed, VRL3 is able to associate with VR1 and may modulate its responses. Hence, not only is VRL3 a thermosensitive ion channel but it may represent an additional vanilloid receptor subunit involved in the formation of heteromeric vanilloid receptor channels.

Amino Acid Sequence↗
PubMed2002

Sema7A is a potent monocyte stimulator.

Sema7A is a recently described member of the semaphorin family that is associated with the cell surface via a glycophosphatidylinositol linkage. This study examined the mRNA expression and biological properties of this protein. Although the expression of Sema7A was demonstrated in lymphoid and myeloid cells, no stimulation of cytokine production or proliferation was evident in B or T cells. In contrast, Sema7A is an extremely potent monocyte activator, stimulating chemotaxis at 0.1 pm and inflammatory cytokine production (interleukin-1 (IL-1beta), tumour necrosis factor-alpha (TNF-alpha), IL-6 and IL-8) and superoxide release at 1-10 pm. Sema7A is less effective at stimulating neutrophils. Sema7A also significantly increases granulocyte-macrophage colony-stimulating factor (GM-CSF) production from monocytes but has no consistent effect on IL-10, IL-12 or IL-18. Sema7A can also induce monocytes toward a dendritic cell morphology. Sema7A is expressed in monocytes and probably released through proteolysis and acts as a very potent autocrine activator of these cells.

Animals↗
PubMed2002

Combined therapy with clopidogrel and aspirin significantly increases the bleeding time through a synergistic antiplatelet action.

OBJECTIVE: Many thromboembolic events occur in patients taking aspirin. Dual therapy with aspirin and clopidogrel may prove effective at reduction of thromboembolic complications. However, the extent to which these two drugs interact may significantly increase the risk of bleeding in open surgery. Because of the increased use of combination antiplatelet therapy in populations with significant atherosclerotic disease, this risk needs to be evaluated by the assessment of the combined effect in vivo of clopidogrel and aspirin on bleeding time and platelet function. OUTCOMES: In seven healthy subjects, addition of low dose clopidogrel (2 x 75 mg) to aspirin (150 mg) therapy significantly increased bleeding time (from 7.6 +/- 3.4 minutes to 17.5 +/- 8.6 minutes; P <.05), with concomitant falls in adenosine diphosphate (ADP)-induced platelet fibrinogen binding and aggregation (P <.05). Increasing the dose of clopidogrel to 300 mg increased bleeding time (to 24.9 +/- 8.5 minutes; P <.05) without significant additional platelet inhibition. There was considerable variability in the individual subject platelet response to the lower dose of clopidogrel. Those patients with the highest ADP response at baseline had the least response, and subjects with a weak response to ADP at baseline achieved maximal platelet inhibition with the low dose of clopidogrel. CONCLUSION: The increases in bleeding times should be considered in combination antiplatelet therapy in patients who undergo open vascular surgery.

Adult↗
PubMed2001

Kinetic modification of the alpha(1I) subunit-mediated T-type Ca(2+) channel by a human neuronal Ca(2+) channel gamma subunit.

1. Voltage-sensitive Ca(2+) channels (VSCCs) are often heteromultimeric complexes. The VSCC subtype specifically expressed by skeletal muscle has long been known to contain a gamma subunit, gamma(1), that is only expressed in this tissue. Recent work, initiated by the identification of the mutation present in the stargazer mouse, has led to the identification of a series of novel potential Ca(2+) channel gamma subunits expressed in the CNS. 2. Based on bioinformatic techniques we identified and cloned the human gamma(2), gamma(3) and gamma(4) subunits. 3. TaqMan analysis was used to quantitatively characterise the mRNA expression patterns of all the gamma subunits. All three subunits were extensively expressed in adult brain with overlapping but subunit-specific distributions. gamma(2) and gamma(3) were almost entirely restricted to the brain, but gamma(4) expression was seen in a broad range of peripheral tissues. 4. Using a myc epitope the gamma(2) subunit was tagged both intracellularly at the C-terminus and on a predicted extracellular site between the first and second transmembrane domains. The cellular distribution was then examined immunocytochemically, which indicated that a substantial proportion of the cellular pool of the gamma(2) subunit was present on the plasma membrane and provided initial evidence for the predicted transmembrane topology of the gamma subunits. 5. Using co-transfection techniques we investigated the functional effects of each of the gamma subunits on the biophysics of the T-type VSCC encoded by the alpha(1I) subunit. This revealed a substantially slowed rate of deactivation in the presence of gamma(2). In contrast, there was no significant corresponding effect of either gamma(3) or gamma(4) on alpha(1I) subunit-mediated currents.

Animals↗
PubMed2001

Characterisation using FLIPR of human vanilloid VR1 receptor pharmacology.

A full pharmacological characterisation of the recently cloned human vanilloid VR1 receptor was undertaken. In whole-cell patch clamp studies, capsaicin (10 microM) elicited a slowly activating/deactivating inward current in human embryonic kidney (HEK293) cells stably expressing human vanilloid VR1 receptor, which exhibited pronounced outward rectification (reversal potential -2.1+/-0.2 mV) and was abolished by capsazepine (10 microM). In FLIPR-based Ca(2+) imaging studies the rank order of potency was resiniferatoxin>olvanil>capsaicin>anandamide, and all were full agonists. Isovelleral and scutigeral were inactive (1 nM-30 microM). The potencies of capsaicin, olvanil and resiniferatoxin, but not anandamide, were enhanced 2- to 7-fold at pH 6.4. Capsazepine, isovelleral and ruthenium red inhibited the capsaicin (100 nM)-induced Ca(2+) response (pK(B)=6.58+/-0.02, 5.33+/-0.03 and 7.64+/-0.03, respectively). In conclusion, the recombinant human vanilloid VR1 receptor stably expressed in HEK293 cells acted as a ligand-gated, Ca(2+)-permeable channel with similar agonist and antagonist pharmacology to rat vanilloid VR1 receptor, although there were some subtle differences.

Alkaloids↗
PubMed2001

A prospective audit of complex wound and graft infections in Great Britain and Ireland: the emergence of MRSA.

BACKGROUND: a number of studies have examined the outcome of complex wound and graft infections, but most include small numbers of patients collected over a prolonged period of time. To date, there is little information on the clinical outcome of infections involving methicillin-resistant Staphylococcus aureus (MRSA). METHODS: between February 1998 and January 1999, two prospective multi-centre audits were performed in order to examine the current outcomes following (1) complex vascular wound infections and (2) graft infections in Britain and Ireland with particular reference to outcome associated with MRSA infection. RESULTS: seventy-five complex wound infections (Szylagyi II and III) were reported, with the commonest single organism being MRSA. Type II infections were associated with a 5% risk of death and/or amputation as opposed to 75% in those with a type III infection. Fifty-five graft infections were reported, with the commonest single organism being MRSA. Overall, 30 (55%) died or underwent amputation. MRSA wound and graft infections were associated with a significantly higher risk of amputation and prolonged hospital stay (but not of death) as compared with MRSA negative patients. CONCLUSIONS: in this audit, MRSA was the commonest single organism cultured in patients with complex wound and graft infections after vascular surgery. This represents a major change in the spectrum of causative organisms relative to other, older published series. MRSA infections contribute towards an increased risk of adverse outcome and prolonged hospital stay.

Cross Infection↗
PubMed2001

Patients' thromboembolic potential between bilateral carotid endarterectomies remains stable over time.

OBJECTIVES: There is limited understanding of the reasons underlying post-CEA carotid thrombosis. Clinicians have often implicated operative technique, such as patch type or shunting, however the evidence for this is limited. We have studied whether it is the patients themselves who are prothrombotic, by studying the rates of emboli detection in patients undergoing bilateral CEAs at separate time points. MATERIALS AND METHODS: Sixteen patients (3 women) underwent CEA during the study period, all of whom were taking aspirin. CEA was performed in a standardised manner throughout the study. All patients were monitored for 3 h postoperatively using a 2 MHz fixed head probe. RESULTS: Those patients who had no emboli detected on TCD after the first operation, had a mean of 2.5 emboli after the second operation. Patients with emboli after the first operation had a mean of 41.3 emboli after the second CEA (MWU test, p=0.02). The dose of aspirin administered did not affect emboli rates. Correlation of the number of emboli detected after the first CEA with the second CEA gave a significant correlation ( p=0.038). CONCLUSIONS: There appear to be factors relating to the patient that places some individuals at an increased risk of thrombotic stroke. Further elucidation of these factors may enable more effective, targeted therapy to be applied in the prevention of arterial thrombosis.

Aspirin↗
PubMed2001

Randomized trial of vein versus Dacron patching during carotid endarterectomy: influence of patch type on postoperative embolization.

PURPOSE: A recent overview indicated that although routine patching is safer than routine primary closure after carotid endarterectomy (CEA), there is no systematic evidence that patch type influences outcome. However, most surgeons still believe that prosthetic patches are probably more thrombogenic than vein patches. This study tested the hypothesis that there was no difference in thrombogenicity between the different patch types. METHODS: A total of 274 patients undergoing 276 CEAs were randomized to either Dacron-patch closure (n = 137) or vein-patch closure (n = 139). All patients with an accessible cranial window were monitored for 3 hours postoperatively with transcranial Doppler scanning (TCD). The number of emboli and rate of embolization were quantified with the requirement for selective dextran therapy to control high rates of postoperative embolization. All patients were assessed postoperatively and again at 30 days by a neurologist, and all patients underwent a duplex examination at 30 days. RESULTS: The 30-day death/any stroke rate was 2.2% for patients in the Dacron-patch group and 3.6% for patients in the vein-patch group (P =.72). Patients in the Dacron-patch group had a higher incidence of postoperative emboli (median, 5; interquartile range, 0-10.5) than patients in the vein-patch group (median, 3; interquartile range, 1-17; P =.028). However, the incidence of detecting more than 50 emboli was virtually identical, and patch type had no effect on the incidence of high-rate, sustained embolization that required dextran therapy (5.3% for Dacron, 3.7% for vein). No patient had a carotid thrombosis at 30 days. CONCLUSION: Sustained, high-rate embolization, previously shown to be highly predictive of progression to carotid thrombosis, appears to be patient dependent, rather than related to patch type.

Aged↗
PubMed2000

Transcranial Doppler-directed Dextran-40 therapy is a cost-effective method of preventing carotid thrombosis after carotid endarterectomy.

OBJECTIVES: perioperative stroke reduces the clinical effectiveness of carotid endarterectomy (CEA). Postoperative thrombotic stroke may be reduced in incidence by the use of transcranial Doppler-directed Dextran-40 therapy. This programme requires the purchase of additional equipment and employment of more staff. This study examined whether this additional financial outlay was cost-effective in terms of saving expenditure by preventing postoperative thrombotic stroke. MATERIALS AND METHODS: data was collected prospectively on a series of 600 consecutive CEAs. The costs of the monitoring programme were analysed over 1- and 5-year periods. Formulae were derived allowing other units to calculate whether this technique will be cost-effective for them. RESULTS: after the introduction of TCD monitoring the postoperative thrombotic stroke rate fell from 2.7% to 0% (8 strokes prevented). Our local unit cost for the treatment of stroke was 25,702 pounds. After allowing for the additional costs of the monitoring programme, we calculate that postoperative TCD has saved 171,393 pounds. CONCLUSIONS: postoperative TCD monitoring is a clinically effective and also cost-effective method of reducing the stroke rate associated with CEA. For units performing more than 50 CEAs per year who experience occasional postoperative carotid thrombosis, its introduction should be considered.

Aged↗
PubMed2000

The Pruitt-Inahara shunt maintains mean middle cerebral artery velocities within 10% of preoperative values during carotid endarterectomy.

OBJECTIVE: The purpose of this study was to assess the ability of the Pruitt-Inahara shunt to maintain adequate middle cerebral artery velocities during carotid endarterectomy. STUDY DESIGN: Prospectively collected data recorded during 548 carotid endarterectomies performed at a single university hospital were analyzed to look at changes in cerebral blood flow velocities at different stages during the procedure. Parallel data relating to blood pressure and end-tidal carbon dioxide were also examined. RESULTS: During the first carotid artery cross clamp, middle cerebral artery velocity fell by 42%. A total of 169 patients (31%) had velocities that fell below 15 cm/s (electrical activity in the brain becomes altered below this level). After shunt insertion, only 2% of patients had middle cerebral artery velocities less than 15 cm/s. In only one patient was the velocity less than 10 cm/s. Increased systolic or diastolic blood pressure raised flow through the shunt significantly (P =.001). When two criteria used for selective shunt use were compared, only a moderate correlation was found between absolute middle cerebral artery velocity after carotid cross clamping and percentage change in middle cerebral artery velocity relative to preclamp values. CONCLUSIONS: The Pruitt-Inahara shunt is able to maintain adequate middle cerebral artery velocity in 98% of patients undergoing carotid endarterectomy. Alterations in blood pressure can significantly affect flow through the shunt.

Blood Flow Velocity↗
PubMed2000

Reducing the risk of carotid surgery: a 7-year audit of the role of monitoring and quality control assessment.

BACKGROUND AND PURPOSE: The current risk of stroke after carotid endarterectomy may be worse than reported in the international trials. Because studies have suggested that most operative strokes follow surgeon error, the aim of the current study was to audit the impact of introducing a strategy of perioperative monitoring and quality control assessment on outcome. METHODS: A total of 500 patients underwent carotid endarterectomy with intraoperative transcranial Doppler scan monitoring, completion angioscopy, and 3 hours of postoperative transcranial Doppler scan monitoring. The last of these guided selective dextran therapy in patients with high rates of postoperative embolization, which in previous series has been shown to be highly predictive of progression to thromboembolic stroke. RESULTS: Intimal flaps were repaired in 3% of patients and luminal thrombus removed in 4% of patients. The rate of intraoperative stroke was 0.2%. A total of 313 patients had more than one embolus detected postoperatively (96% within 2 hours of flow restoration), but only 22 patients had sustained embolization requiring dextran. Embolization ceased in all but one patient receiving dextran, although the dose had to be increased in seven patients (36%). One patient was unable to receive adequate dextran therapy because of severe cardiac failure. Overall, the 30-day death/stroke rate was 2.2%, no patient had a perioperative stroke because of carotid thrombosis, and the rate of ipsilateral embolic stroke was 0.8%. Most complications resulted from cardiac pathology or intracranial hemorrhage. CONCLUSIONS: A program of monitoring and quality control assessment has been associated with a 60% decrease in the operative risk in comparison with that observed before implementation of the protocol.

Clinical Protocols↗
PubMed2000

Assessment of the thigh cuff technique for measurement of dynamic cerebral autoregulation.

BACKGROUND AND PURPOSE: Dynamic methods of measuring cerebral autoregulation have become an accepted alternative to static evaluation. This article aims to describe a set of data collected from healthy volunteers by a dynamic method, the purpose being to qualify and quantify expected results for those who may be designing a study using this technique. METHODS: Cerebral blood flow velocity (CBFV) (measured by transcranial Doppler) and arterial blood pressure (Finapres) were recorded in 16 normal subjects before, during, and after the induction of a blood pressure drop (release of bilateral thigh cuffs). This procedure was repeated 6 times for each subject. A mathematical model was applied to the data to generate an autoregulatory index (ARI) with values between 0 and 9. RESULTS: The ARI values for this sample population follow a normal distribution, with a mean+/-SD of 4.98+/-1.06 (n=15). Analysis of the cumulative mean ARI values of all subjects showed an exponential-type convergence of ARI toward the sample mean as the number of test iterations increased. The population average blood pressure drop on thigh cuff release was 26.4+/-7.1 mm Hg (n=16), occurring in 4.6+/-1. 7 seconds. The corresponding population average drop for CBFV was 15. 6+/-5.8 cm/s, taking 2.5+/-1.0 seconds. No significant trend was noted in the measurements as the number of test iterations increased. The correlation between the predicted and actual CBFV, having a mean value of 0.76+/-0.19, showed evidence of a nonlinear relationship to ARI values. Significant correlation was also found between ARI and (1) arterial blood pressure before cuff release and (2) the magnitude of the drop in CBFV on cuff release. CONCLUSIONS: The distribution of ARI values is not significantly different from normal. At least 3 iterations of the test procedure should be performed and averaged to obtain the mean ARI for each subject. There is no significant evidence of physiological accommodation as the number of test iterations increases. The effects of mean blood pressure and the magnitude of the change in CBFV should be considered as possible covariates when ARI data are analyzed.

Adult↗
PubMed1999

In situ replacement of infected aortic grafts with rifampicin-bonded prostheses: the Leicester experience (1992 to 1998)

PURPOSE: Prosthetic graft infection after aortic aneurysm surgery is a life-threatening complication. Treatment options include total graft excision and extra-anatomic bypass grafting or in situ replacement of the graft. The latter option is gaining increasing popularity, but the long-term outcome remains uncertain, particularly in light of the increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA). We performed a prospective nonrandomized study to assess the outcome after graft excision and in situ replacement with a rifampicin-bonded prosthesis for the treatment of major aortic graft infection. METHODS: In a 6-year period from January 1992 to December 1997, 11 patients (eight men, three women) with major aortic graft infection underwent total graft excision and in situ replacement with a rifampicin-bonded prosthesis. The median age of the patients was 66 years (range, 49 to 78 years). Four patients had a hemorrhage from an aortoenteric fistula, three had a retroperitoneal abscess, two had graft occlusion, one had a perigraft collection shown by means of computed tomography, and one had a ruptured suprarenal false aneurysm. Organisms were cultured from 10 patients. RESULTS: MRSA was isolated in two patients, both of whom had originally undergone repair of a ruptured abdominal aortic aneurysm. Two patients died (18.2%) within 30 days, and three patients (27.6%) had nonfatal complications (peritoneal candidiasis, transient renal impairment, and profound anorexia). Two patients died late in the follow-up period. Seven patients remain alive and clinically free of infection. CONCLUSION: The long-term results after total graft excision and in situ replacement with a rifampicin-bonded prosthesis appear to be favorable. However, MRSA aortic graft infection appears to be associated with a poor prognosis.

Aged↗