bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined effects of aspirin and the novel antiplatelet agent clopidogrel on platelet function in vivo and in vitro
Authors: Payne D A , Hayes P D , Bell P R , Goodall A H , Naylor A R 
Published: March 2003

Abstract

Background
The platelet adenosine 5′-diphosphate (ADP) receptor antagonist clopidogrel has proved an effective antiplatelet agent in the prevention of arterial thrombosis. In the vast majority of studies clopidogrel has been used as an alternative to aspirin, but the widespread use of aspirin, and the different modes of actions of the two drugs, makes it important to determine the safety and efficacy of using both drugs in combination. This study reports the effect of this drug combination on bleeding times and platelet function in humans.

Methods
The study was conducted in normal, healthy subjects to evaluate the effects of different doses of clopidogrel on bleeding time, platelet aggregation and activation, above a baseline of standard aspirin therapy. Seven normal men (mean age 30 years) were given aspirin (150 mg) for 3 days. Subjects received clopidogrel (75 mg) at 24 and 48 h, followed by a third dose of clopidogrel (300 mg) on day 3.

Results
The combination of aspirin plus clopidogrel leads to a significant reduction in platelet function relative to aspirin alone (P &lt; 0·05), and is associated with a significant increase in the bleeding time (P &lt; 0·05). The response to collagen was similarly affected. Platelet fibrinogen binding in response to both ADP and thrombospondin-related adhesive protein was reduced only partially by aspirin, but significantly reduced by both doses of clopidogrel (P &lt; 0·05 for all). P-selectin expression in response to both agonists was also reduced, but not significantly. Basal levels of fibrinogen binding, P-selectin, glycoprotein (GP) IIb–IIIa and GPIb expression were not affected by treatment.

Conclusion
Blocking both the cyclo-oxygenase and ADP pathways of platelet activation has a profound effect on platelet response to agonists, which may offer significant potential benefit in preventing thrombotic events relative to aspirin alone. Achieving the correct balance between haemostasis and thrombosis with these useful agents will require further study.
Autologous thrombin-induced thrombosis of pseudoaneurysms
Authors: Quarmby J W , Engelke C , Chitolie A , Morgan R A , Belli A-M 
Published: March 2003

Abstract

Background
This study was designed to evaluate the use of autologous thrombin (as opposed to commercial bovine thrombin) in the percutaneous obliteration of postcatheterization femoral pseudoaneurysms.

Methods
Ten consecutive patients with a symptomatic femoral pseudoaneurysm following cardiac catheterization underwent duplex assessment. All ten pseudoaneurysms were at least 2 cm in the longest axis. Autologous thrombin was isolated from 60 ml blood, under sterile conditions. The autologous thrombin was injected into the cavity of the pseudoaneurysm under ultrasonographic guidance. The progression of thrombosis was monitored throughout with ultrasonography. After the procedure, the femoral arteries were examined for thrombosis propagation or embolization. The foot pulses and ankle pressures were checked. Samples of the thrombin isolates were analysed to quantify thrombin activity. Duplex assessment was repeated at 6 weeks.

Results
All ten patients had successful thrombosis of the pseudoaneurysm, although three required repeat thrombin injections within 24 h. No long-term symptoms were identified relating to the thrombosis and no patient required surgery. There was no evidence of recanalization at 6 weeks on duplex imaging, and no signs of infection.

Conclusion
Autologous thrombin-induced thrombosis of pseudoaneurysms is a simple, safe, painless and inexpensive procedure. This novel approach, which uses the patient's own thrombin, is cheaper than bovine thrombin; it also avoids the risk of viral contamination or anaphylaxis from commercial thrombin.
Comparison of primary closure with dacron patch angioplasty in early and late restenosis after carotid endarterectomy
Authors: Gerrard D J , Hatrick A H , Dourado R A , Patel H , Irvine A T , Burnand K G 
Published: March 2003

Abstract

Background
The primary closure of carotid arteriotomy has a high incidence of intraoperative residual stenosis following carotid endarterectomy.

Methods
Completion angiograms in a consecutive series of 197 patients undergoing carotid endarterectomy were reviewed. All operations were performed under general anaesthesia with routine shunt insertion and middle cerebral artery transcranial Doppler monitoring. The first 117 patients had primary closure of the arteriotomy and the last 80 all had patch closure. An independent radiologist, who was unaware of the procedure performed, randomly assessed the intraoperative angiograms. All patients have been followed by 3-monthly duplex screening for 1 year. Results were assessed with the χ2 test.

Results
The stroke and death rate of 7 per cent in the primary closure group was significantly higher than the 1 per cent stroke and death rate in the patched group (P &lt; 0·05). Perioperative angiograms scored 0–20 per cent residual stenosis in 75 per cent of the primary closures, compared with 89 per cent in the patched group (P &lt; 0·05). Some 25 per cent of the primary closures were considered unsatisfactory, compared with 11 per cent of the patched closures. Restenosis greater than 50 per cent at 1 year was significantly higher in the primary closure group (33 versus 19 per cent; P &lt; 0·05).

Conclusion
Patch closure results in a better technical result than primary closure, as judged by radiological appearance, and reduces the overall stroke and death rate. Restenosis is significantly lower at 1 year.
Midterm results of a single endovascular device for repair of an abdominal aortic aneurysm: one centre's experience of the Vanguard device
Authors: Holtham S J , Dugdill S , Rose J D G , Lees T A , Wyatt M G 
Published: March 2003

Abstract

Background
The aim of the study was to evaluate the midterm results of the Vanguard device.

Methods
All deployments performed in a single centre with follow-up according to EUROSTAR criteria were reviewed.

Results
Fifty-five patients underwent deployment of a Vanguard device between December 1995 and July 1999. All stents were implanted successfully, with a perioperative mortality rate of 5 per cent (three of 55 patients). Twelve systemic complications (23 per cent) and three access site complications (6 per cent) were observed. Predischarge computed tomograms revealed one type I and five type II endoleaks. Eleven patients died during follow-up (median 23·4 (range 6–48) months) (ten unrelated, one ruptured abdominal aortic aneurysm). The 2-year survival rate was 70 per cent. Eleven occluded graft limbs (22 per cent; median onset 18 months (range from 24 h to 36 months)), one graft migration and eight late endoleaks (16 per cent; median onset 24 (range 3–42) months) were observed. The 2-year intervention-free survival rate was 68 per cent, with an endoleak-free survival rate of 84 per cent. Median (range) neck diameter increased from 20 (15–23) to 23 (17–27) mm at 24 months (P &lt; 0·01).

Conclusion
The onset of late endoleak and limb occlusion suggests that follow-up is essential, even after 36 months. The increasing neck diameter may prove significant with regard to long-term fixation of the proximal device.
Outcome analysis of over 1000 episodes of limb ischaemia treated by peripheral thrombolysis
Authors: Braithwaite B D , Whitman B , Foy C 
Published: March 2003

Abstract

Background
In the past 10 years, 13 hospitals with an interest in peripheral arterial thrombolysis have collected information on 1064 episodes of thrombolysis used to treat some 933 patients. The aim of the database was to identify clinical factors at the time of admission to hospital and relate them to the patients' outcome.

Methods
After verification of the database, a regression analysis was done in three stages: univariate analysis, logistic regression including the initial success of thrombolysis, and logistic regression analysis excluding initial success. The endpoints were amputation-free survival (AFS), survival but with amputation, and death. Statistical analysis was performed with SPSS software (SPSS, Chicago, Illinois, USA).

Results
The overall AFS was 72·9 per cent; 12·6 per cent of events resulted in amputation and 12·9 per cent of patients died. Univariate analysis showed that patients receiving warfarin had a survival advantage, whereas those with diabetes and ischaemia that caused sensory loss were significantly more likely to require amputation. Logistic regression analysis confirmed the above effects of diabetes and ischaemia. Major haemorrhage occurred in 8 per cent of events, but there was a significantly increased risk if the patient had a history of peripheral vascular disease (P = 0·007) or presented with graft thrombosis (P = 0·001). Stroke occurred in 2·4 per cent of events; a greater incidence occurred in patients with a duration of ischaemia of less than 8 h.

Conclusion
Further detailed analysis of this large and unique database should help clinicians to refine the indications for peripheral thrombolysis in the management of acute leg ischaemia.
Impact of angioplasty on infrainguinal bypass for critical ischaemia of the leg
Authors: Evoy D , Sultan S , Colgan M P , Moore D , Shanik G 
Published: March 2003

Abstract

Background
Both angioplasty and infrainguinal bypass procedures may be used to achieve limb salvage in patients with critical ischaemia. The authors investigated the effect of the introduction of angioplasty on the frequency with which infrainguinal bypass was performed and, second, the changes in outcome of infrainguinal bypass following the introduction of angioplasty.

Methods
All patients had critical ischaemia of the leg. Three patient groups were studied: 215 patients undergoing infrainguinal bypass before the introduction of angioplasty (1986–1991), 216 patients who had infrainguinal bypass after the introduction of angioplasty (1993–1998) and 193 patients undergoing angioplasty in the same 5-year interval (1993–1998).

Results
The age and risk profile of the three groups was identical. The overall caseload increased by 19 per cent following the introduction of angioplasty. Primary and secondary patency rates were superior for bypass compared with angioplasty, but were similar for the two bypass groups (5-year primary patency rate 60 per cent versus 18-month primary patency rate 45 per cent; 5-year secondary patency rate 80 per cent versus 18-month secondary patency rate 60 per cent). By 18 months 26 per cent of patients having angioplasty had gone on to have bypass. The limb salvage rate of 90 per cent at 1 year was similar for all groups. Survival was significantly higher in the group of patients undergoing bypass from 1993 to 1998 compared with the other two groups (80 versus 60 per cent; P &lt; 0·0002).

Conclusion
The introduction of angioplasty has increased overall workload. Angioplasty has a lower patency rate than bypass but a comparable limb salvage rate, making it a suitable alternative to bypass in the management of patients with critical ischaemia.
P-POSSUM models for abdominal aortic aneurysm surgery
Authors: Boyle J R , Prytherch D R , Payne S P , Pemberton R M , Sutton G L 
Published: March 2003

Abstract

Background and methods
POSSUM (Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity) data on 444 (213 emergency, 231 elective) admissions for abdominal aortic aneurysm (AAA) surgery between August 1993 and July 2000 were analysed using the P-POSSUM equation for general surgery and the P-POSSUM equations developed for the Vascular Surgical Society of Great Britain and Ireland (physiological and operative and physiology only).

Results
All three equations successfully modelled the elective admissions but failed to fit the emergency admissions and the elective and emergency admissions combined. This suggests that admission method (not a POSSUM data item) is an important factor for patients with AAA. However, with these data it was not possible to generate a model, including admission method, that successfully modelled the combined elective and emergency data. Emergency AAAs had to be treated separately. The 213 emergency admissions were divided into two groups by operation date. The first 106 (training set) were used to form logistic regression models following the P-POSSUM methodology. These models were found successfully to fit the remaining 107 records (test set) on prospective application, as shown in the Table.

Conclusion
Emergency AAAs appear to be fundamentally different from elective AAAs and other vascular cases, and require their own distinct risk model. The ability to model risk for elective AAAs using a physiology-only risk model could perhaps be used to optimize the timing of operation as well as informing all concerned of the risks involved.
Risk modelling for carotid endarterectomy
Authors: Kuhan G , Gardiner E , Abidia A , Chetter I , Renwick P , Johnson B F , Wilkinson A R , McCollum P T 
Published: March 2003

Abstract

Background
A 30-day stroke or death rate of 3–10 per cent has been reported in patients undergoing carotid endarterectomy (CEA). The aim of this study was to identify the risk factors that influenced the outcome and to develop a logistic regression model that can aid in the comparative audit of CEA.

Methods
Some 836 CEAs performed by four vascular surgeons from 1992 to 1999 were analysed. The median age of the population was 69 (range 38–86) years, and the male: female ratio was 1·6. Multiple logistic regression was used to model the effect of 15 risk factors on the 30-day stroke and death rate. The outcome after risk adjustment was compared for four surgeons and two vascular units.

Results
The overall 30-day stroke and death rate was 3·9 per cent. Regression modelling identified heart disease, diabetes and stroke at presentation as significant risk factors. A risk score of 1 was assigned to each of these risk factors to produce a logistic regression equation (where P is the probability of 30-day stroke or death):
ln(P/1 − P) = 0·9294(risk score) − 4·2726.
The observed 30-day stroke and death rate for four vascular surgeons was 3·0, 4·0, 4·2 and 4·3, and for two vascular units was 3·9 and 3·9. Differences between the surgeons and the vascular units were not statistically significant after allowing for risk adjustment using this model.

Conclusion
Multiple logistic regression models can successfully identify patients at higher risk from CEA, and aid in the comparative audit of surgeons and vascular units.
Economic evaluation of a randomized clinical trial of haemodilution with cell salvage in aortic surgery
Authors: Haynes S L , Torella F , Wong J C L , Dalrymple K , James M , McCollum C N 
Published: March 2003

AbstractBackgroundThis study evaluated the costs of acute normovolaemic haemodilution (ANH) and intraoperative cell salvage (ICS) versus homologous blood transfusion in aortic surgery in a prospective multicentre randomized trial.MethodsOne hundred and forty-five patients were randomized either to standard transfusion practice (homologous) or to a combination of ANH and ICS (autologous). Costs for each inpatient admission were identified. Cell salvage costs were assigned on the assumption that 50 operations were done each year employing a trained cell salvage operator. The results were analysed statistically using bias-corrected bootstrap analysis.ResultsPatients who had transfusion of homologous blood received some 251 units and those having a homologous transfusion received 103 units (P = 0·008). There was no difference in morbidity, mortality and duration of hospital stay. Transfusion-related mean costs were similar at £340 for patients having a homologous transfusion and £357 for those receiving autologous blood (mean difference £17 (95 per cent confidence interval (c.i.) −£184 to £174); P not significant). There was also no significant difference in mean overall costs: £5859 for homologous and £5384 for autologous transfusion (mean difference −£475 (95 per cent c.i. −£2231 to £1342)). Sensitivity analysis showed that costs remained similar for 20 and 150 operations per annum. Exclusion of a dedicated cell salvage operator reduced autologous transfusion costs but did not have a significant impact on overall cost.ConclusionAutologous transfusion is cost neutral in aortic surgery even when surgical activity is low.
Therapeutic relevance of breast cancer micrometastases in sentinel lymph nodes
Authors: Noguchi M 
Published: March 2003

AbstractBackground and methodsThis review examines the various methods of detecting occult breast cancer metastasis in the sentinel lymph node (SLN). The prognostic relevance of such micrometastases and isolated tumour cells, and their impact on stage migration and decision making with respect to axillary dissection and adjuvant systemic therapy, are discussed.ResultsExamination of SLNs by serial section with haematoxylin and eosin and/or immuno histochemical staining significantly increases the detection rate of micrometastases, even in patients with very small (T1) tumours. However, the prognostic relevance of isolated tumour cells and small micrometastases is uncertain. Moreover, deciding which patients might benefit from axillary dissection is complicated by the fact that adjuvant radiotherapy and systemic chemotherapy alone may eradicate most micrometastases.ConclusionOngoing randomized trials comparing the results of SLN biopsy alone with those of axillary dissection should answer the question of whether isolated tumour cells and small micrometastases are clinically relevant. This should also indicate which patients with SLN micrometastasis are likely to benefit from axillary dissection. In this sense, SLN biopsy must be considered still to be at an investigative stage; outwith clinical trials complete axillary dissection should be performed on all patients with SLN micrometastasis.
Degradation of apoptotic cells and fragments in HL‐60 suspension cultures after induction of apoptosis by camptothecin and ethanol
Authors: Baisch H. , Bollmann H. , Bornkessel S. 
Published: March 2003

Abstract. Early indicators of apoptosis in mammalian cells are membrane potential breakdown (loss) in mitochondria (MPLM), chromatin condensation, DNA degradation, and phosphatidylserine exposure (PSE) on the outside plasma membrane. One aim of the present study was to determine the kinetics of these characteristics. These changes were measured by flow cytometry using the following methods: membrance potential of mitochondria was analysed using Mito Tracker Green and Red, PSE was analysed using annexin‐V‐FITC staining simultaneously with propidium iodide (PI) to detect membrane permeability; chromatin condensation was measured using the acid denaturation Acridine Orange (AO) method; DNA degradation was studied by the sub G1 method and the terminal transferase dUTP nick end‐labelling (TUNEL) assay (labelling of strand breaks). HL‐60 cells were induced to apoptosis by 3% ethanol and 1.5 μM camptothecin (CAM) and the kinetics of the apoptotic cells were measured. The same kinetics were found for chromatin condensation and DNA degradation indicating that these changes appeared at approximately the same time after induction. The MPLM and PSE kinetics showed a considerably later increase indicating that MPLM occurred downstream of DNA degradation and that plasma membrane changes occurred downstream of MPLM.The main aim of the study was to follow the fate of apoptotic cells after the appearance of the initial characteristics. The lifetime of apoptotic cells was studied by chase experiments. The inducing drug was removed after 4 h treatment and the disappearance of apoptoses recorded. An exponential decay was measured with a half life (T½) of 17.8 h. As a corollary from these experiments, camptothecin was found to induce apoptosis also in G1 and G2 phase cells, however, it took much longer to occur than in S phase cells.Using labelling of the plasma membrance with a fluorescent cell membrance linker, it was possible to show that the majority of apoptotic bodies as well as condensed apoptotic cells contain DNA and membrance. The degradation of these apoptotic bodies follows similar kinetics as those of the condensed apoptotic cells. The membrane remained considerably stable, there was no further loss in the next 7 days, after the first day when the apoptotic characteristics develop. It is concluded that the apoptosis programme is completed within a day and no further steps follow.
Chaperones in cell cycle regulation and mitogenic signal transduction: a review
Authors: Helmbrecht K. , Zeise E. , Rensing L. 
Published: March 2003

Chaperones/heat shock proteins (HSPs) of the HSP90 and HSP70 families show elevated levels in proliferating mammalian cells and a cell cycle‐dependent expression. They transiently associate with key molecules of the cell cycle control system such as Cdk4, Wee‐1, pRb, p53, p27/Kip1 and are involved in the nuclear localization of regulatory proteins. They also associate with viral oncoproteins such as SV40 super T, large T and small t antigen, polyoma large and middle S antigen and EpsteinBarr virus nuclear antigen. This association is based on a J‐domain in the viral proteins and may assist their targeting to the pRb/E2F complex. Small HSPs and their state of phosphorylation and oligomerization also seem to be involved in proliferation and differentiation. Chaperones/HSPs thus play important roles within cell cycle processes. Their exact functioning, however, is still a matter of discussion.HSP90 in particular, but also HSP70 and other chaperones associate with proteins of the mitogen‐activated signal cascade, particularly with the Src kinase, with tyrosine receptor kinases, with Raf and the MAP‐kinase activating kinase (MEK). This apparently serves the folding and translocation of these proteins, but possibly also the formation of large immobilized complexes of signal transducing molecules (scaffolding function).
Vitamin E inhibition of normal mammary epithelial cell growth is associated with a reduction in protein kinase Cα activation
Authors: Sylvester P. W. , McIntyre B. S. , Gapor A. , Briski K. P. 
Published: March 2003

Abstract.Tocopherols and tocotrienols represent the two subclasses within the vitamin E family of compounds. However, tocotrienols are significantly more potent than tocopherols in suppressing epidermal growth factor (EGF)‐dependent normal mammary epithelial cell growth. EGF is a potent mitogen for normal mammary epithelial cells and an initial event in EGF‐receptor mitogenic‐signalling is protein kinase C (PKC) activation. Studies were conducted to determine if the antiproliferative effects of specific tocopherol and tocotrienol isoforms are associated with a reduction in EGF‐receptor mitogenic signalling and/or PKC activation. Normal mammary epithelial cells isolated from midpregnant BALB/c mice were grown in primary culture, and maintained on serum‐free media containing 10 ng/mL EGF as a mitogen, and treated with various doses (0–250 µm) of α‐, γ‐, or δ‐tocopherol or α‐, γ‐, or δ‐tocotrienol. Treatment with growth inhibitory doses of δ‐tocopherol (100 µm), α‐tocotrienol (50 µm), or γ‐ or δ‐tocotrienol (10 µm) did not affect EGF‐receptor levels, EGF‐induced EGF‐receptor tyrosine kinase activity, or total intracellular levels of PKCα. However, these treatments were found to inhibit EGF‐induced PKCα activation as determined by its translocation from the cytosolic to membrane fraction. Treatment with 250 µmα‐ or γ‐tocopherol had no affect on EGF‐receptor mitogenic signalling or cell growth. These findings demonstrate that the inhibitory effects of specific tocopherol and tocotrienol isoforms on EGF‐dependent normal mammary epithelial cell mitogenesis occurs downstream from the EGF‐receptor and appears to be mediated, at least in part, by a reduction in PKCα activation.