Combined aspirin and cilostazol treatment is associated with reduced platelet aggregation and prevention of exercise-induced platelet activation.

BACKGROUND: Cilostazol has proven efficacy in increasing walking distance in claudicants, but it has not been demonstrated to be more effective than placebo in secondary cardiovascular prevention. The direct effect of exercise on platelet function remains less well defined. We have investigated the effect of combination treatment with aspirin and cilostazol on platelet activity in claudicants subjected to repeated treadmill exercise. METHODS: Nineteen claudicants completed a double-blind, randomised, controlled, cross-over trial. Each subject received a 2-week course of aspirin (75mg) and placebo and aspirin and cilostazol (100mg twice daily). Following each 2-week treatment period, patients participated in a standardised treadmill test (3.2kmh(-1), 10 degrees incline) walking to maximal claudication distance. The exercise was repeated thrice in total, and blood was sampled before and after exercise. Platelet activation was measured using free platelet counting aggregation, flow cytometry for surface markers of platelet activation and soluble P-selectin assay. RESULTS: Compared to aspirin and placebo, combination treatment with aspirin and cilostazol was associated with reduced arachidonic-acid-induced platelet aggregation (p<0.01, Wilcoxon signed-rank test). Aspirin and placebo treatment were associated with elevated P-selectin expression, platelet-monocyte aggregation and reduced CD42b expression (p<0.05, Wilcoxon signed-rank test) post-exercise. No difference was seen in spontaneous platelet aggregation whilst soluble P-selectin was reduced post-exercise with combination treatment with aspirin and cilostazol (p<0.05, Wilcoxon signed-rank test). CONCLUSIONS: Combination treatment with aspirin and cilostazol results in suppression of platelet activation and reduces the effect of exercise on platelets. The benefit seen may be a result of cilostazol enhancing the inhibitory effect of aspirin on the cyclo-oxygenase pathway.

Platelet monocyte aggregates and monocyte chemoattractant protein-1 are not inhibited by aspirin in critical limb ischaemia.

OBJECTIVES: Platelet monocyte aggregates (PMA) and monocyte chemoattractant protein-1 (MCP-1) play a significant role in atherosclerotic disease but the effect of aspirin and their role in peripheral arterial disease (PAD) requires further investigation. We have compared p-selectin, PMA and MCP-1 in patients with PAD treated with aspirin (75 mgs daily), with age matched controls not treated with aspirin. MATERIALS AND METHODS: Using flow cytometry and ELISA, P-selectin, PMA and MCP-1 were compared in 3 populations; healthy controls (n=12), intermittent claudication (n=19) and critical limb ischaemia (CLI), (n=10). RESULTS: P-selectin was significantly higher in CLI patients (3.48% positive) compared to the claudicants (1. 36% positive) and the controls (1.76% positive). PMA levels were significantly higher for CLI population (44.5% positive) compared to the claudicants (20.48% positive) and the controls (28.33% positive). MCP-1 levels expression was significantly higher for the CLI patients (175.4 pg/mL) compared to the claudicants (76.1 pg/mL) and the controls (117.0 pg/mL). CONCLUSION: Despite aspirin treatment CLI patients have higher platelet activation and MCP-1 expression than controls and claudicants. With increasing severity of disease aspirin is unable to suppress markers of platelet activation and pro-atherosclerotic chemokine expression which may represent another form of aspirin resistance.

Treadmill exercise in claudicants on aspirin results in improved antioxidant status but only minimal platelet activation.

The consequence of exercise on platelets remains controversial and adverse effects may result from repeated ischaemia reperfusion injury. We investigated platelet activation (platelet P-selectin (PS), and activated glycoprotein (Gp) IIb/IIIa), platelet-monocyte aggregates (PMA) and total plasma antioxidant status (TPAS) in claudicants after exercise. Twenty claudicants, taking 75 mg of aspirin daily, were subjected to repeated treadmill testing (3 km/h, 10% inclination). Blood was sampled before and after exercise. Activated GpIIb/IIIa, PS and PMA were quantified with flow cytometry. TPAS was quantified using a decolourisation assay. Percent positive cells for PS (pre-exercise 3.76% vs. 40 min post-exercise 4.10%; P < 0.05) and platelet-monocyte aggregates (pre-exercise: 25.31% vs. 40 min post-exercise 26.99%; P < 0.05) were significantly higher after exercise. Relative median fluorescence (RMF) for activated GpIIb/IIIa was significantly higher 40 min after exercise (pre-exercise: 3.04 vs. 40 min post-exercise: 4.01; P < 0.05). TPAS was significantly higher post-exercise (pre-exercise: 1.31 mmol/l vs. 1 min post-exercise: 1.40 mmol/l and 40 min post-exercise: 1.38 mmol/l; P < 0.01). Following moderate exercise, 'aspirin treated claudicants' show marginal platelet activation, PMA formation and a favourable improvement in antioxidant status. Further studies are required to assess the effect of additional antiplatelet agents and the significance of platelet-monocyte interactions. The possibility that aspirin contributes to the TPAS changes following exercise needs to be investigated.

Life-style modification in peripheral arterial disease.

OBJECTIVE: To review the published evidence supporting the use of life-style modification in peripheral arterial disease (PAD). DESIGN: A systematic search of the medical literature was performed for relevant studies. MATERIALS: The publications obtained were then searched for randomised clinical trials which reported end-points of mortality or major cardiovascular event rates with various life-style modifications. RESULTS: Only one randomised controlled trial was found reporting relevant end-points. Other trials were of other end-points such as walking distance or biochemical markers. CONCLUSIONS: There is a lack of randomised controlled data proving the benefit of life-style modification in improving mortality and reducing cardiovascular events in patients with PAD. Despite this there is sufficient evidence to recommend some life-style modification as part of the overall approach to risk reduction in these patients. There is compelling evidence to support smoking cessation, increased exercise and improved diet.

MRSA infected pseudoaneurysms of the radial artery.

The use of radial artery catheters for real-time blood pressure monitoring and arterial blood gas sampling has become commonplace in both intensive care and high dependency units. Although this procedure is relatively safe, it can be complicated by local infection leading to pseudoaneurysm formation. In this report we describe three cases of pseudoaneurysm formation following prolonged radial catheter placement, with evidence of local methicillin resistant staphylococcus aureus (MRSA) infection. With the growing problem of in-hospital MRSA colonisation, the report aims to emphasize the need for vigilance for this complication and reinforce the importance of careful asepsis. In all cases the pseudoaneurysms were successfully treated with local ligation of the radial artery, without subsequent ischaemic complications. Allen's test was performed to ensure sufficient collateral circulation prior to surgery.

Intravascular brachytherapy: a systematic review of its role in reducing restenosis after endovascular treatment in peripheral arterial disease.

INTRODUCTION: Intravascular brachytherapy (IVBT) utilises the percutaneous insertion of a radioactive source to inhibit myointimal hyperplasia in arteries treated by balloon angioplasty or stenting. A systematic review was performed of trials of IVBT in patients with Peripheral Arterial Disease (PAD). METHODS: Search strategy - the reviewers searched Medline, Embase, the Cochrane Peripheral Vascular Diseases Group trials register, DARE, CCT and NHS EED for clinical studies and trials of adjuvant IVBT in PAD. Two reviewers assessed trial quality independently. RESULTS: Fourteen clinical trials were identified by the search, representing five clinical studies (all allocated D for not randomised) and one randomised controlled trial (allocated A). The randomised trial showed a benefit for IVBT compared with placebo (OR 0.35, 95% CI 0.24-0.53). In the non-randomised studies, 12 month cumulative patency rates ranged from 60-87%. There were few technical complications. In the only report involving IVBT and routine concurrent stent insertion acute thrombosis occurred in 7 (21%) of patients. CONCLUSION: Early reports have confirmed the safety and technical feasibility of IVBT. However, follow-up is too short at present to assess the durability and long-term complications of this new therapeutic option.

Intravascular brachytherapy for peripheral vascular disease.

BACKGROUND: International treatment of atherosclerotic narrowed and blocked arteries involves either bypassing the blockage using a graft, widening it from the inside with a balloon, a procedure known as percutaneous transluminal angioplasty (PTA), or providing a strut to hold the vessel open, known as a stent. All of these treatments are however limited by the high numbers that fail within a year. Intravascular brachytherapy (IVBT) is the application of radiation directly to the site of vessel narrowing. It is known to inhibit the processes that lead to restenosis (narrowing) of vessels and grafts after treatment. OBJECTIVES: The objective of this review was to assess the efficacy and complications of intravascular brachytherapy on maintaining patency after angioplasty or stent insertion in native vessels or bypass grafts of the iliac or infrainguinal arteries. SEARCH STRATEGY: The reviewers searched the Cochrane Peripheral Vascular Diseases Group Trials Register (last searched 5 July 2002), the Cochrane Controlled Trials Register (last searched Issue 2, 2002), MEDLINE, EMBASE and reference lists of relevant articles. SELECTION CRITERIA: Randomised trials of the use of brachytherapy as an adjunct to the treatment of patients with peripheral arterial diseases (PAD) or stenosed bypass grafts of the iliac or infrainguinal arteries arteries versus the procedure without brachytherapy. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Adverse events information was collected from the trials. MAIN RESULTS: One trial was identified which met the inclusion criteria, involving 117 patients, mean age 71 years (43-89). The trial compared PTA versus PTA and IVBT in patients with long-segment de novo or restenotic lesions or occlusions of any length in the femoropopliteal artery. Results were provided at six month follow up in 107 patients (54 PTA alone, 53 PTA+IVBT). The results favoured adjuvant IVBT in preventing restenosis/occlusion with an odds ratio (OR) of 0.35 (95% CI 0.24 to 0.53). Analysis of subgroups showed a significant benefit of IVBT in non-diabetics, OR 0.22 (95% CI 0.07 to 0.69), in those undergoing IVBT in restenotic lesions, OR 0.32 (95% CI 0.10 to 1.01), occlusive lesions, OR 0.19 (95% CI 0.06 to 0.62) and lesions in which the PTA length was greater than 10cm, OR 0.24 (95% CI 0.09 to 0.62). REVIEWER'S CONCLUSIONS: Results from the only trial available would suggest that IVBT is effective at improving the patency of femoropopliteal arteries undergoing PTA in the short-term, particularly in non-diabetics with long occlusions (>10cm).

Venous boot construction for a distal prosthetic bypass.

Autologous vein should be used at all costs for infrainguinal grafting. There is, nevertheless, a need for other materials in tertiary referral centres whose practice is becoming more complex. Polytetrafluoroethylene (PTFE) has been the prosthesis of choice for most surgeons, but results were poor for grafts to crural arteries. The use of a venous boot, cuff, or collar appeared to improve these results, but only one randomized trial has been performed. This article describes the St Mary's venous boot, which purports to combine the advantages of the other techniques.

Effects of intraduodenal glucose infusion on gastric myoelectrical activity and antropyloroduodenal motility.

Intraduodenal nutrient infusions cause an inhibition of antral motility and an increase in pyloric motility. The involvement of gastric myoelectrical activity in this intestinogastric feedback was studied. Electrogastrography and antropyloroduodenal manometry were performed in 10 healthy volunteers. The effects of 20-mininfusions of 25% glucose (4 kcal/min) and saline were compared. Intraduodenal glucose infusions caused a decrease in the power of the dominant frequency in the electrogastrogram (P = 0.028), but the frequency itself remained unchanged. The total number of dysrhythmias increased (P = 0.035). An inhibition of antral motor activity (P = 0.001), an increase in the number of isolated pyloric pressure waves (P = 0.027), and an increase in basal pyloric tone (P = 0.001) were simultaneously recorded. The change in power during glucose infusion correlated positively with the change in the antral motility index (rs = 0.50, P = 0.001). It is concluded that inhibition of gastric myoelectrical activity is one of the mechanisms underlying an inhibition of motor activity in the gastric antrum.

U.S. health care reform: will it change postgraduate surgical education?

The principal goals of the pending health care reform initiatives in the United States are improving access to health care and controlling its costs. There are multiple proposals designed to reach these goals. Regardless of the final result, health care reform is likely to have significant implications for postgraduate surgical education. The teaching environment is already rapidly changing. Present environmental influences include the explosion of surgical knowledge, demographic changes, expansion of regulatory requirements from within the health care delivery system and within surgery as a discipline, societal and cultural changes, and economic pressures. Current and pending concerns prompt several questions: What should we teach? Where do we teach? How long should it take? Who are our learners? How do we evaluate our educational programs? Who should pay? A number of predictable changes affecting surgical education are proposed. New, more complex technologies will result in increased surgical specialization. Demands on surgical education will require that it be shorter, more relevant, more efficient, more effective, and more accountable. Surgical manpower requirements must be more clearly defined. Better and more relevant measures of clinical outcomes will be developed. Use of improved informational technology to manage clinical activity will expand. Solutions to the problem of foreign medical graduates will be clarified. The issue of who pays for surgical education will require resolution with some new and creative results. A proposal for shorter and more effective surgical residency is advocated.

Klatskin tumors: radiological and imaging findings in eleven patients.

A retrospective study of 11 patients with Klatskin tumor is presented. The series includes 3 men and 8 women with a mean age of 71 years (range: 61-84 years). Histologic examination revealed a well-differentiated cholangiocarcinoma in 7 cases, an undifferentiated type in 3 and a sclerosing type in one. Ultrasound plays an increasing role in setting a directive diagnosis. Preoperative localisation of the tumor and status of the intrahepatic bile ducts are best depicted with cholangiography. CT findings are non specific, but are useful for an adequate pre- and post-treatment staging.