Relationship between 'on-treatment platelet reactivity', shear stress, and micro-embolic signals in asymptomatic and symptomatic carotid stenosis.

BACKGROUND: Assessment of 'high on-treatment platelet reactivity (HTPR)' could enhance understanding of the pathophysiology of first or recurrent vascular events in carotid stenosis patients on antiplatelet therapy. METHODS: This prospective, multi-centre study assessed antiplatelet-HTPR status and its relationship with micro-emboli signals (MES) in asymptomatic vs. symptomatic ≥ 50-99% carotid stenosis. Platelet function/reactivity was assessed under 'moderately high shear stress' with the PFA-100® and 'low shear stress' with VerifyNow® and Multiplate® analysers. Bilateral 1-h transcranial Doppler ultrasound of the middle cerebral arteries classified patients as MES + ve or MES - ve. RESULTS: Data from 34 asymptomatic patients were compared with 43 symptomatic patients in the 'early phase' (≤ 4 weeks) and 37 patients in the 'late phase' (≥ 3 months) after TIA/ischaemic stroke. Median daily aspirin doses were higher in early symptomatic (225 mg; P < 0.001), but not late symptomatic (75 mg; P = 0.62) vs. asymptomatic patients (75 mg). There was a lower prevalence of aspirin-HTPR in early (28.6%; P = 0.028), but not late symptomatic (38.9%; P = 0.22) compared with asymptomatic patients (56.7%) on the PFA-100®, but not on the VerifyNow® or Multiplate® (P ≤ 0.53). Early symptomatic patients had a higher prevalence of aspirin-HTPR on the PFA-100® (28.6%) vs. VerifyNow® (9.5%; P = 0.049), but not Multiplate® assays (11.9%, P = 0.10). There was no difference in aspirin-HTPR prevalence between any symptomatic vs. asymptomatic MES + ve or MES - ve subgroup. DISCUSSION: Recently symptomatic moderate-severe carotid stenosis patients had a lower prevalence of aspirin-HTPR than their asymptomatic counterparts on the PFA-100®, likely related to higher aspirin doses. The prevalence of antiplatelet-HTPR was positively influenced by higher shear stress levels, but not MES status.

Increased Leucocyte-Platelet Complex Formation in Recently Symptomatic versus Asymptomatic Carotid Stenosis Patients and in Micro-emboli Negative Subgroups.

INTRODUCTION: Cerebral micro-embolic signals (MES) predict risk of stroke in carotid stenosis patients. However, MES-negative 'recently symptomatic patients' also have a higher stroke risk than 'asymptomatic patients'. Differences in platelet activation status may contribute to this disparity in risk. METHODS: This prospective, observational study assessed platelet biomarkers and their relationship with MES in asymptomatic versus symptomatic moderate (≥50-69%) or severe (≥70-99%) carotid stenosis patients. Full blood count parameters were measured and whole-blood flow cytometry was used to quantify platelet surface CD62P and CD63 expression and leucocyte-platelet complex formation. Bilateral simultaneous transcranial Doppler ultrasound of the middle cerebral arteries classified patients as 'MES positive' or 'MES negative'. RESULTS: Data from 34 asymptomatic patients were compared with those from 43 symptomatic patients in the 'early phase' (≤ 4 weeks) and 37 of these symptomatic patients in the 'late phase' (≥ 3 months) after transient ischaemic attack/ischaemic stroke. There were no differences in %CD62P or %CD63 expression between early or late symptomatic and asymptomatic patients overall (p > 0.05). The percentage of lymphocyte-platelet complexes was higher in early symptomatic than in asymptomatic patients (2.8 vs. 2.16%; p < 0.001). MES were more commonly observed in early symptomatic (31.4%; p = 0.027) but not in late symptomatic (6.7%; p = 0.996) versus asymptomatic patients (7.1%). The percentage of lymphocyte-platelet complexes was higher in early symptomatic than in asymptomatic MES-negative patients (2.7 vs. 2.17%; p = 0.02). CONCLUSION: These data add to the evidence that leucocyte-platelet complex formation/platelet activation is increased in recently symptomatic versus asymptomatic patients, and may contribute to the pathogenesis of first and subsequent strokes in carotid stenosis patients, including those who are MES negative.

Profile of von Willebrand factor antigen and von Willebrand factor propeptide in an overall TIA and ischaemic stroke population and amongst subtypes.

INTRODUCTION: Von Willebrand factor propeptide (VWF:Ag II) is proposed to be a more sensitive marker of acute endothelial activation than von Willebrand factor antigen (VWF:Ag). Simultaneous data on VWF:Ag and VWF:Ag II profiles are very limited following TIA and ischaemic stroke. METHODS: In this prospective, observational, case-control study, plasma VWF:Ag and VWF:Ag II levels were quantified in 164 patients≤4weeks of TIA or ischaemic stroke (baseline), and then ≥14days (14d) and ≥90days (90d) later, and compared with those from 27 healthy controls. TIA and stroke subtyping was performed according to the TOAST classification. The relationship between VWF:Ag and VWF:Ag II levels and platelet activation status was assessed. RESULTS: 'Unadjusted' VWF:Ag and VWF:Ag II levels were higher in patients at baseline, 14d and 90d than in controls (p≤0.03). VWF:Ag levels remained higher in patients than controls at baseline (p≤0.03), but not at 14d or 90d after controlling for differences in age or hypertension, and were higher in patients at baseline and 90d after controlling for smoking status (p≤0.04). 'Adjusted' VWF:Ag II levels were not higher in patients than controls after controlling for age, hypertension or smoking (p≥0.1). Patients with symptomatic carotid stenosis (N=46) had higher VWF:Ag and VWF:Ag II levels than controls at all time-points (p≤0.002). There was no significant correlation between platelet activation status and VWF:Ag or VWF:Ag II levels. CONCLUSIONS: VWF:Ag and VWF:Ag II levels are increased in an overall TIA and ischaemic stroke population, especially in patients with recently symptomatic carotid stenosis. VWF:Ag II was not superior to VWF:Ag at detecting acute endothelial activation in this cohort and might reflect timing of blood sampling in our study.

Increased thrombin generation potential in symptomatic versus asymptomatic moderate or severe carotid stenosis and relationship with cerebral microemboli.

INTRODUCTION: The importance of thrombin generation in the pathogenesis of TIA or stroke and its relationship with cerebral microembolic signals (MES) in asymptomatic and symptomatic carotid stenosis has not been comprehensively assessed. METHODS: Plasma thrombin generation parameters from patients with moderate or severe (≥ 50%) asymptomatic carotid stenosis were compared with those from patients with symptomatic carotid stenosis in the early (≤ 4 weeks) and late phases (≥ 3 months) after TIA or stroke in this prospective, pilot observational study. Thrombin generation profile was longitudinally assessed in symptomatic patients with data at each time point. Bilateral transcranial Doppler ultrasound monitoring of the middle cerebral arteries was performed whenever possible to classify patients as MES-positive or MES-negative. RESULTS: Data from 31 asymptomatic, 46 'early symptomatic' and 35 'late symptomatic' patients were analysed. Peak thrombin (344.2 nM vs 305.3 nM; p = 0.01) and endogenous thrombin potential (1772.4 vs 1589.7; p = 0.047) were higher in early symptomatic than asymptomatic patients. Peak thrombin production decreased in symptomatic patients followed up from the early to late phase after TIA or stroke (339.7 nM vs 308.6 nM; p = 0.02). Transcranial Doppler ultrasound data were available in 25 asymptomatic, 31 early symptomatic and 27 late symptomatic patients. Early symptomatic MES-positive patients had a shorter 'time-to-peak thrombin' than asymptomatic MES-positive patients (p=0.04), suggesting a more procoagulant state in this early symptomatic subgroup. DISCUSSION: Thrombin generation potential is greater in patients with recently symptomatic than asymptomatic carotid stenosis, and decreases over time following TIA or stroke associated with carotid stenosis. These data improve our understanding of the haemostatic/thrombotic biomarker profile in moderate-severe carotid stenosis.

Longitudinal assessment of von Willebrand factor antigen and von Willebrand factor propeptide in response to alteration of antiplatelet therapy after TIA or ischaemic stroke.

The impact of commencing or changing antiplatelet therapy on von Willebrand factor antigen (VWF:Ag) and von Willebrand factor propeptide (VWF:Ag II) levels has not been comprehensively assessed following TIA or ischaemic stroke. In this pilot, longitudinal, observational analytical study, VWF:Ag and VWF:Ag II levels were simultaneously quantified in platelet poor plasma by ELISA in patients within 4 weeks of TIA or ischaemic stroke (baseline), and then 14 days (14d) and >90 days (90d) after altering antiplatelet therapy. Ninety-one patients were recruited. Eighteen were initially assessed on no antiplatelet therapy, and then after 14d (N = 17) and 90d (N = 8) on aspirin monotherapy; 21 patients were assessed on aspirin and after 14d and 90d on clopidogrel; 52 were assessed on aspirin monotherapy, and after 14d and 90d on aspirin and dipyridamole combination therapy. VWF:Ag, VWF:Ag II levels and VWF:Ag/VWF:Ag II ratio were unchanged at 14d and 90d in the overall study population (p ≥ 0.1). VWF:Ag and VWF:Ag II levels remained stable at 14d and 90d after commencing aspirin (p ≥ 0.054), and after changing from aspirin to clopidogrel (p ≥ 0.2). Following the addition of dipyridamole MR to aspirin, there was a significant reduction in VWF:Ag levels at 14d (p = 0.03) and 90d (p = 0.005), but not in VWF:Ag II levels (p ≥ 0.3). The addition of dipyridamole to aspirin led to a persistent reduction in VWF:Ag but not in VWF:Ag II levels, suggesting that dipyridamole may inhibit release of platelet-derived VWF:Ag following TIA or ischaemic stroke.

Increased endothelial activation in recently symptomatic versus asymptomatic carotid artery stenosis and in cerebral microembolic-signal-negative patient subgroups.

BACKGROUND AND PURPOSE: von Willebrand factor propeptide (VWF:Ag II) is potentially a more sensitive marker of acute endothelial activation than von Willebrand factor antigen (VWF:Ag). These biomarkers have not been simultaneously assessed in asymptomatic versus symptomatic carotid stenosis patients. The relationship between endothelial activation and cerebral microembolic signals (MESs) detected on transcranial Doppler ultrasound is unknown. METHODS: In this multicentre observational analytical study, plasma VWF:Ag and VWF:Ag II levels in patients with ≥50% asymptomatic carotid stenosis were compared with those from patients with ≥50% symptomatic carotid stenosis in the 'early' (≤4 weeks) and 'late' (≥3 months) phases after transient ischaemic attack or ischaemic stroke. Endothelial activation was also longitudinally assessed in symptomatic patients during follow-up. Transcranial Doppler ultrasound monitoring classified patients as MES-positive or MES-negative. RESULTS: Data from 31 asymptomatic patients were compared with those from 46 early symptomatic and 35 late phase symptomatic carotid stenosis patients, 23 of whom had undergone carotid intervention. VWF:Ag II levels were higher in early (12.8 µg/ml; P < 0.001), late (10.6 µg/ml; P = 0.01) and late post-intervention (10.6 µg/ml; P = 0.038) symptomatic patients than asymptomatic patients (8.9 µg/ml). VWF:Ag levels decreased in symptomatic patients followed up from the early to late phase after symptom onset (P = 0.048). Early symptomatic MES-negative patients had higher VWF: Ag II levels (13.3 vs. 9.0 µg/ml; P < 0.001) than asymptomatic MES-negative patients. CONCLUSIONS: Endothelial activation is enhanced in symptomatic versus asymptomatic carotid stenosis patients, in early symptomatic versus asymptomatic MES-negative patients, and decreases over time in symptomatic patients. VWF:Ag II levels are a more sensitive marker of endothelial activation than VWF:Ag levels in carotid stenosis. The potential value of endothelial biomarkers and concurrent cerebral MES detection at predicting stroke risk in carotid stenosis warrants further study.

Increased platelet activation in early symptomatic vs. asymptomatic carotid stenosis and relationship with microembolic status: results from the Platelets and Carotid Stenosis Study.

BACKGROUND: Cerebral microembolic signals (MES) may predict increased stroke risk in carotid stenosis. However, the relationship between platelet counts or platelet activation status and MES in symptomatic vs. asymptomatic carotid stenosis has not been comprehensively assessed. SETTING: University teaching hospitals. METHODS: This prospective, pilot observational study assessed platelet counts and platelet activation status, and the relationship between platelet activation and MES in asymptomatic vs. early (≤ 4 weeks after TIA/stroke) and late phase (≥ 3 months) symptomatic moderate or severe (≥ 50%) carotid stenosis patients. Full blood count measurements were performed, and whole blood flow cytometry was used to quantify platelet surface activation marker expression (CD62P and CD63) and circulating leucocyte-platelet complexes. Bilateral simultaneous transcranial Doppler ultrasound monitoring of the middle cerebral arteries was performed for 1 h to classify patients as MES positive or MES negative. RESULTS: Data from 31 asymptomatic patients were compared with 46 symptomatic patients in the early phase, and 35 of these patients were followed up to the late phase after symptom onset. The median platelet count (211 vs. 200 × 10(9)  L(-1) ; P = 0.03) and the median percentage of lymphocyte-platelet complexes was higher in early symptomatic than asymptomatic patients (2.8 vs. 2.4%; P = 0.001). The percentage of lymphocyte-platelet complexes was higher in early symptomatic than in asymptomatic patients with ≥ 70% carotid stenosis (P = 0.0005) and symptomatic patients recruited within 7 days of symptom onset (P = 0.028). Complete TCD data were available in 25 asymptomatic, 31 early phase symptomatic and 27 late phase symptomatic patients. Twelve per cent of asymptomatic vs. 32% of early phase symptomatic (P = 0.02) and 19% of late phase symptomatic patients (P = 0.2) were MES positive. Early symptomatic MES-negative patients had a higher percentage of lymphocyte-platelet complexes than asymptomatic MES-negative patients (2.8 vs. 2.3%; P = 0.0085). DISCUSSION: Recently, symptomatic carotid stenosis patients have had higher platelet counts (potentially reflecting increased platelet production, mobilization or reduced clearance) and platelet activation status than asymptomatic patients. MES were more frequently detected in early symptomatic than asymptomatic patients, but the differences between late symptomatic and asymptomatic groups were not significant. Increased lymphocyte-platelet complex formation in recently symptomatic vs. asymptomatic MES-negative patients indicates enhanced platelet activation in this early symptomatic subgroup. Platelet biomarkers, in combination with TCD, have the potential to aid risk-stratification in asymptomatic and symptomatic carotid stenosis patients.

High on-treatment platelet reactivity on commonly prescribed antiplatelet agents following transient ischaemic attack or ischaemic stroke: results from the Trinity Antiplatelet Responsiveness (TRAP) study.

BACKGROUND AND PURPOSE: The prevalence of ex vivo 'high on-treatment platelet reactivity' (HTPR) to antiplatelet regimens in patients with ischaemic cerebrovascular disease (CVD) is uncertain. METHODS: HTPR was assessed with PFA-100 collagen-epinephrine (C-EPI) and collagen-ADP (C-ADP) cartridges. Platelet activation (CD62P, CD63 and leucocyte-platelet complex formation) was assessed with whole-blood flow cytometry. Patients were assessed at baseline [≤ 4 weeks of transient ischaemic attack (TIA) or ischaemic stroke], and at 14 days and ≥ 90 days after changing treatment from (i) no medication to aspirin monotherapy (N = 26) or (ii) aspirin to clopidogrel monotherapy (N = 22). HTPR was defined in a novel, 'longitudinal fashion' as failure to prolong relevant closure times compared with the patient's 'baseline value' before he/she underwent an antiplatelet change by more than twice the coefficient of variation of the assay. RESULTS: (i) C-EPI closure times increased at 14 days and 90 days after commencing aspirin (P = 0.002); 24% at 14 days and 18% at 90 days demonstrated HTPR on aspirin. (ii) C-ADP closure times increased at 14 days (P = 0.001) but not 90 days (P = 0.09) after changing from aspirin to clopidogrel; 41% at 14 days, and 35% at 90 days demonstrated HTPR on clopidogrel. Platelet activation was unaffected by aspirin (P = 0.09). The percentage neutrophil-platelet complexes decreased at 14 days (P = 0.02), but this reduction was not maintained 90 days after changing to clopidogrel (P = 0.3). No patient had a recurrent vascular event during prospective follow-up. CONCLUSIONS: Longitudinal definitions of HTPR in patients with ischaemic CVD who are undergoing a change in antiplatelet therapy have the potential to provide more clinically meaningful information than traditional 'cross-sectional definitions' of HTPR which are usually based on the comparison of patients' values with those in healthy controls. Using our novel, longitudinal definition of HTPR, the PFA-100 could be used to monitor ex vivo responsiveness to aspirin, and larger, prospective studies are warranted to assess the clinical predictive value of this and other platelet function tests in patients with ischaemic CVD.

Longitudinal assessment of thrombin generation potential in response to alteration of antiplatelet therapy after TIA or ischaemic stroke.

The impact of changing antiplatelet therapy on thrombin generation potential in patients with ischaemic cerebrovascular disease (CVD) is unclear. We assessed patients within 4 weeks of TIA or ischaemic stroke (baseline), and then 14 days (14d) and >90 days (90d) after altering antiplatelet therapy. Thrombin generation was assessed in platelet poor plasma. Ninety-one patients were recruited. Twenty-four were initially assessed on no antiplatelet therapy, and then after 14d (N = 23) and 90d (N = 8) on aspirin monotherapy; 52 were assessed on aspirin monotherapy, and after 14 and 90 days on aspirin and dipyridamole combination therapy; 21 patients were assessed on aspirin and after 14 days (N = 21) and 90 days (N = 19) on clopidogrel. Peak thrombin generation and endogenous thrombin potential were reduced at 14 and 90 days (p ≤ 0.04) in the overall cohort. We assessed the impact of individual antiplatelet regimens on thrombin generation parameters to investigate the cause of this effect. Lag time and time-to-peak thrombin generation were unchanged at 14 days, but reduced 90 days after commencing aspirin (p ≤ 0.009). Lag time, peak thrombin generation and endogenous thrombin potential were reduced at both 14 and 90 days after adding dipyridamole to aspirin (p ≤ 0.01). Lag time was reduced 14 days after changing from aspirin to clopidogrel (p = 0.045), but this effect was not maintained at 90 days (p = 0.2). This pilot study did not show any consistent effects of commencing aspirin, or of changing from aspirin to clopidogrel on thrombin generation potential during follow-up. The addition of dipyridamole to aspirin led to a persistent reduction in peak and total thrombin generation ex vivo, and illustrates the diverse, potentially beneficial, newly recognised 'anti-coagulant' effects of dipyridamole in ischaemic CVD.

The cost utility of a multi-disciplinary foot protection clinic (MDFPC) in an Irish hospital setting.

BACKGROUND: Foot ulceration which may result in lower limb amputation is one of the most feared complications among patients with diabetes and the prevention of both ulceration and amputation is a major challenge facing the health service. Many studies have proposed dedicated diabetic foot teams as the future of diabetic foot care. AIMS: We aimed to quantify the cost benefit and sustainability of a multi-disciplinary foot protection clinic (MDFPC) in an Irish university hospital setting. METHODS: A dedicated bi-weekly consultant-led MDFPC including Vascular Surgery, Endocrinology, Orthopaedic Surgery, Podiatry, Orthotics and Tissue Viability was established in June 2008. RESULTS: Between 2006 and 2010, a total of 221 lower limb procedures (major/minor amputations and debridement) were performed. The number of major amputations decreased from 12 during the control period (2 years before the clinic) to 7 in the study period (2 years after the clinic). After costing all activity associated with the clinic, there was an overall saving of €114,063 per year associated with the introduction of the MDFPC. CONCLUSION: This is the first study in an Irish context, and one of few international studies, to demonstrate that an aggressive-coordinated approach to diabetic foot care is both cost effective and clinically efficient in reducing the burden of foot-related complications in a diabetic population.

Popliteo-pedal bypass surgery for critical limb ischemia.

BACKGROUND: Critical limb ischaemia due to distal arterial disease represents a significant challenge. Randomised controlled evidence suggests that open surgery may be superior to endovascular intervention but there is limited data on the specific clinical cohort with exclusively infra-popliteal disease. AIM: We analysed indications for, and outcome from all, popliteo-pedal bypass procedures performed between July 1998 to November 2008. PATIENTS AND METHODS: Twenty-eight bypass procedures were performed in 24 patients. Autologous vein was used exclusively. The proximal anastomosis was to the below-knee popliteal artery in all the patients; the distal anastomosis was to plantar artery (n = 15) or dorsalis pedis artery (n = 13). Mean patient age was 63.Eight years of age (range 37-92 years). Indications for surgery were tissue loss (n = 21) and rest pain (n = 7). Ultrasound graft surveillance was performed every 6-months. RESULTS: Using life table analysis, primary graft patency was 63.3% at 1-, 3- and 5-years and secondary patency (after three interventions) was 74.6% at 1-, 3- and 5-years. Limb salvage rate was 81.8% after 1-, 3- and 5-years as all five limb amputations were performed in the first 3-months following the surgery. Overall survival was 75, 75 and 47.1% at 1-, 3- and 5-years, respectively. The major amputation free survival rate was 54.2, 54.2 and 21.3% at 1-, 3- and 5-years, respectively. Seventy-nine percent (n = 19) patients were diabetic. CONCLUSION: Our data supports popliteo-pedal bypass as an effective treatment for distal vascular disease. Comparison with endovascular treatment in a randomised trial needs to be performed.

Changing trends in surgical treatment of carotid disease in Ireland (1996-2003).

BACKGROUND: Carotid endarterectomy (CEA) is a well-established method of stroke prevention in patients with symptomatic, high-grade internal carotid artery stenosis. AIMS: To assess the change in carotid surgery practice in health board regions in Ireland over two different time periods in the past 11 years (1996-1998/2001-2003). METHODS: Numbers of discharges of patients with a procedure code CEA (38.12) between 1996-1998 and 2001-2003 were obtained from the Hospital In-Patient Enquiry (HIPE) database maintained by the Economic and Social Research Institute (ESRI). Population data was obtained from national censuses. RESULTS: There has been considerable change in the level of carotid surgery activity in specific health board regions between the two periods. CONCLUSIONS: Still no region comes close to achieving levels of CEA recommended by population studies. This is important in the context of the MRC asymptomatic carotid surgery trial (ACST), as the numbers suitable for CEA will probably increase further in the future.

Impact of the informed consent process on patients' understanding of varicose veins and their treatment.

AIM: It is particularly important that patients have reasonable understanding of the risks, benefits and nature of elective surgery. This study sought to analyse this level of understanding in patients undergoing varicose vein surgery METHODS: Eighty two patients completed a questionnaire in the vascular outpatient clinic and were asked to complete a telephone questionnaire following the clinic. RESULTS: Pain (n = 46) was the primary reason patients considered varicose vein surgery followed by appearance (n = 32). Most patients felt that varicose veins placed them at high risk of leg ulcers (n = 46) and DVT (n = 41). A high level of expectation that surgery would significantly affect pain and flares was recorded. While the outpatient visit did not materially change these misconceptions, an educational leaflet significantly enhanced the recall of complications (p = 0.028) in patients who remembered receiving a leaflet. CONCLUSION: Patients attending varicose vein clinics have an unrealistic expectation of the benefits of surgery and fail to understand the benign nature of their condition. The outpatient process has little effect on patient-held beliefs.

Anatomical variation at the saphenofemoral junction.

BACKGROUND: This study was designed to document the surgical anatomy of the saphenofemoral junction (SFJ). METHODS: The anatomy of the SFJ was recorded diagrammatically in 2089 consecutive groin dissections performed to treat primary varicose veins. The number of primary tributaries, bifid systems, junctional tributaries and the relationship of the external pudendal artery (EPA) to the long saphenous vein (LSV) were recorded. RESULTS: The LSV was bifid in 18.1 per cent of legs. The number of tributaries at the SFJ varied from one to ten. In 33.4 per cent one or more (junctional) tributaries joined the LSV or common femoral vein deep to the deep fascia. The EPA crossed anterior to 16.8 per cent of LSVs. In 4.6 per cent it passed posterior to one large tributary or trunk of a bifid LSV and anterior to the second trunk, making identification of the second trunk particularly difficult. CONCLUSION: A thorough understanding of the anatomical variations of the SFJ is important in ensuring that the junction is managed safely and adequately in patients with varicose veins. Failure to appreciate these variations may account for a significant proportion of inadequate primary varicose vein surgery.

Current treatments for axillary hyperhidrosis.

Primary hyperhidrosis affects up to 1% of the population and has a significant negative impact on quality of life. It affects the axillae in approximately 80% of cases. Hyperhidrosis results from excessive sympathetic stimulation of the eccrine sweat glands: the various treatment modalities available target points along the pathway between the central nervous system and the peripheral gland. The first line of treatment is topical aluminium chloride, which is effective in the majority of cases. Alternative treatments such as systemic anti-cholinergics and iontophoresis have significant disadvantages, while surgical sympathectomy has been regarded as the gold-standard in treatment of this condition. Recently, attention has focused on the use of intradermal botulinum toxin for the treatment of axillary hyperhidrosis. This is a highly effective, minimally-invasive treatment with few side effects, and is now recommended as the treatment of choice in isolated axillary hyperhidrosis

Staged resection or primary anastomosis for obstructing lesions to the left colon.

The management of obstructing left-sided colonic and rectal lesions has traditionally been by a staged procedure. The introduction of 'on-table lavage', has made primary resection and anastomosis of the large bowel feasible for patients presenting as emergencies. We have studied the perioperative course of 28 patients who presented with left colonic obstruction to determine whether primary anastomosis conferred additional morbidity. The patients ranged in age from 29 to 89 years (mean 66 years) at presentation. The ASA status of patients was comparable in both groups (Table 1). Fourteen patients underwent resection, on-table lavage, and primary anastomosis (PA) and 14 a Hartmann's procedure (HP). The mean operative time for the PA procedure was 200 minutes compared to 110 minutes for the HP group. There was no significant difference in the postoperative complication rate nor mean hospital stay rate for the primary procedures between the two groups. There was no clinical anastomotic leak in patients undergoing primary anastomosis. However secondary surgery for patients undergoing colorectal reconnection conferred added morbidity for patients who had a HP. We conclude that resection, on-table lavage, and primary anastomosis is safe in the management of left-sided colonic obstruction and in most cases is the treatment of choice.

Endothelium derived relaxing factor is absent in experimental in situ vein grafts.

Endothelium derived relaxing factor (EDRF) is a local modulator of vasomotor tone in most blood vessels. Reversed vein grafts in several animal models do not produce EDRF when stimulated, and have been shown to have altered responses to several vasoconstrictors. The preservation of EDRF production and vasomotor function in in situ vein grafts was examined in this study. In situ vein grafts of the right carotid artery were performed in five mongrel dogs using external jugular vein. The contralateral jugular vein was used as a control. The vessels were harvested after 6 weeks and rings from the central portion of each vessel studied in vitro in an organ bath. Following cumulative dose response curves to noradrenaline, the rings were precontracted with the estimated ED50 (50% effective dose) dose of noradrenaline, and cumulative doses of acetylcholine added to induce EDRF release. The vein grafts were hypersensitive to noradrenaline, the ED50 being reduced from 8.7 +/- 2.7 x 10(-7) M in the jugular veins to 1.7 +/- 0.7 x 10(-7) M in the vein grafts (p < 0.05). All of the jugular vein segments relaxed in response to acetylcholine with a mean maximal relaxation of 42 +/- 6% of precontraction. None of the vein graft segments relaxed in response to acetylcholine despite the presence of an intact endothelium on scanning electron microscopy, but did relax in response to calcium ionophore. The results indicate that in situ vein grafts, like reversed grafts, fail to produce EDRF in response to acetylcholine. The grafts are also hypersensitive to noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)