Rivaroxaban versus aspirin for secondary prevention of ischaemic stroke in patients with cancer: a subgroup analysis of the NAVIGATE ESUS randomized trial.

BACKGROUND AND PURPOSE: Cancer is a frequent finding in ischaemic stroke patients. The frequency of cancer amongst participants in the NAVIGATE ESUS randomized trial and the distribution of outcome events during treatment with aspirin and rivaroxaban were investigated. METHODS: Trial participation required a recent embolic stroke of undetermined source. Patients' history of cancer was recorded at the time of study entry. During a mean follow-up of 11 months, the effects of aspirin and rivaroxaban treatment on recurrent ischaemic stroke, major bleeding and all-cause mortality were compared between patients with cancer and patients without cancer. RESULTS: Amongst 7213 randomized patients, 543 (7.5%) had cancer. Of all patients, 3609 were randomized to rivaroxaban [254 (7.0%) with cancer] and 3604 patients to aspirin [289 (8.0%) with cancer]. The annual rate of recurrent ischaemic stroke was 4.5% in non-cancer patients in the rivaroxaban arm and 4.6% in the aspirin arm [hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.78-1.24]. In cancer patients, the rate of recurrent ischaemic stroke was 7.7% in the rivaroxaban arm and 5.4% in the aspirin arm (HR 1.43, 95% CI 0.71-2.87). Amongst cancer patients, the annual rate of major bleeds was non-significantly higher for rivaroxaban than aspirin (2.9% vs. 1.1%; HR 2.57, 95% CI 0.67-9.96; P for interaction 0.95). All-cause mortality was similar in both groups. CONCLUSIONS: Our exploratory analyses show that patients with embolic stroke of undetermined source and a history of cancer had similar rates of recurrent ischaemic strokes and all-cause mortality during aspirin and rivaroxaban treatments and that aspirin appeared safer than rivaroxaban in cancer patients regarding major bleeds. www.clinicaltrials.gov (NCT02313909).

Randomized clinical trial comparing surgery, endovenous laser ablation and ultrasound-guided foam sclerotherapy for the treatment of great saphenous varicose veins.

BACKGROUND: Endovenous ablation techniques and ultrasound-guided foam sclerotherapy (UGFS) have largely replaced open surgery for treatment of great saphenous varicose veins. This was a randomized trial to compare the effect of surgery, endovenous laser ablation (EVLA) (with phlebectomies) and UGFS on quality of life and the occlusion rate of the great saphenous vein (GSV) 12 months after surgery. METHODS: Patients with symptomatic, uncomplicated varicose veins (CEAP class C2-C4) were examined at baseline, 1 month and 1 year. Before discharge and at 1 week, patients reported a pain score on a visual analogue scale. Preoperative and 1-year assessments included duplex ultrasound imaging and the Aberdeen Varicose Vein Severity Score (AVVSS). RESULTS: The study included 214 patients: 65 had surgery, 73 had EVLA and 76 had UGFS. At 1 year, the GSV was occluded or absent in 59 (97 per cent) of 61 patients after surgery, 71 (97 per cent) of 73 after EVLA and 37 (51 per cent) of 72 after UGFS (P < 0·001). The AVVSS improved significantly in comparison with preoperative values in all groups, with no significant differences between them. Perioperative pain was significantly reduced and sick leave shorter after UGFS (mean 1 day) than after EVLA (8 days) and surgery (12 days). CONCLUSION: In comparison with open surgery and EVLA, UGFS resulted in equivalent improvement in quality of life but significantly higher residual GSV reflux at 12-month follow-up.

Rapid action in the Palaeogene, the relationship between phenotypic and taxonomic diversification in Coenozoic mammals.

A classic question in evolutionary biology concerns the tempo and mode of lineage evolution. Considered variously in relation to resource utilization, intrinsic constraints or hierarchic level, the question of how evolutionary change occurs in general has continued to draw the attention of the field for over a century and a half. Here we use the largest species-level phylogeny of Coenozoic fossil mammals (1031 species) ever assembled and their body size estimates, to show that body size and taxonomic diversification rates declined from the origin of placentals towards the present, and very probably correlate to each other. These findings suggest that morphological and taxic diversifications of mammals occurred hierarchically, with major shifts in body size coinciding with the birth of large clades, followed by taxonomic diversification within these newly formed clades. As the clades expanded, rates of taxonomic diversification proceeded independently of phenotypic evolution. Such a dynamic is consistent with the idea, central to the Modern Synthesis, that mammals radiated adaptively, with the filling of adaptive zones following the radiation.

The mid-M1 segment of the middle cerebral artery is a cutoff clot location for good outcome in intravenous thrombolysis.

BACKGROUND AND PURPOSE: We studied the impact of the location of the thrombus (internal carotid artery, proximal M1 segment, distal M1 segment, M2 segment, and M3 segment of the middle cerebral artery) in predicting the clinical outcome of patients treated with intravenous thrombolytic therapy (<3 h) in a retrospective cohort. METHODS: Anterior circulation thrombus was detected with computed tomography angiography in 105 patients. Baseline clinical and radiological information was collected and entered into logistic regression analysis to predict favorable clinical outcome (3-month modified Rankin Scale from 0 to 2 was a primary outcome measure). RESULTS: Three months after stroke, there was a significant increase in mortality (32% vs. 3%, P < 0.001) and functional dependency (82% vs. 29%, P < 0.001) in patients with internal carotid artery or proximal M1 segment of the middle cerebral artery thrombus compared to a more distal occlusion. In the regression analysis, after adjusting for National Institutes of Health Stroke Scale, age, sex, and onset-to-treatment time, the clot location was an independent predictor of good clinical outcome (P = 0.001) and exhibited dose-response type behavior when moving from a proximal vessel position to a more distal one. When the location was dichotomized, a cutoff between the proximal and the distal M1 segments best differentiated between good and poor clinical outcome (OR = 16.0, 95% CI 3.9-66.2). CONCLUSIONS: The outcome of acute internal carotid artery or proximal M1 segment of the middle cerebral artery occlusion is generally poor even if treated with intravenous thrombolysis. Alternative revascularization strategies should be considered. Vascular imaging at the admission is required to guide this decision.

PAD as a risk factor for mortality among patients with elevated ABI--a clinical study.

OBJECTIVE: This study aims to evaluate mortality across ankle-brachial index (ABI) values and to assess the association between elevated ABI, peripheral arterial disease (PAD) and mortality. DESIGN: This is a retrospective clinical study. MATERIAL AND METHODS: A total of 2159 patients referred with a suspicion of PAD had their ABI and toe brachial index (TBI) measured by photoplethysmography. ABI > or =1.3 was considered falsely elevated while TBI <0.60 was the diagnostic criterion for PAD among the subjects. The cohort was followed up for total and cardiovascular mortality until 30 June 2008, by record linkage with the National Causes-of-Death Register. RESULTS: The average follow-up time was 39 months. A total of 576 (26.7%) patients died during the follow-up. Mortality was highest in the elevated ABI group (35.7% for elevated ABI; 30.1% for low ABI and 16.0% for normal ABI, p < 0.001). There was a greater than twofold risk of total, and an increased but statistically non-significant risk of, cardiovascular mortality among patients with elevated ABI. Similar risk ratios were noted for the low ABI (< or =0.9) group. More pronounced associations were observed at both ends of the scale when ABI was divided into sub-categories. The overall survival was significantly worse for the elevated ABI group than for both the normal and the low-ABI group (p < 0.01 and p = 0.013, respectively). PAD was found to be independently associated with both total and cardiovascular mortality among those with elevated ABI (odds ratio (OR): 2.21; 95% confidence interval (CI): 1.01-4.85 and OR: 4.90; 95% CI: 1.50-16.04, respectively). CONCLUSIONS: The association between elevated ABI and poor survival is similar to that of low ABI. PAD appears to be an independent risk factor for mortality among patients with elevated ABI.

Prolonged healing of venous leg ulcers: the role of venous reflux, ulcer characteristics and mobility.

OBJECTIVE: To assess whether a difference in venous reflux pattern, ulcer size or duration, regular medications or the daily use of walking aids can predict the healing of a chronic venous leg ulcer (VLU). METHOD: In this prospective, randomised, single-centre study, 110 consecutive patients with chronic leg ulcers were assessed. Ninety-nine patients met the inclusion criteria and a controlled, conservative 3-month treatment period was initiated, in which 90 patients were managed with standardised local treatment combined with compression therapy. In this group, 62 VLUs healed within 12 weeks and 28 were still open after 12 weeks. The study group consisted of 22 patients with non-healed ulcers and a control group (n=28), which was selected randomly from the healers. In both groups, venous reflux profiles were assessed using colour-flow duplex imaging. RESULTS: The study and control groups did not differ in smoking habits, age, gender or daily oral medications. On average, the healing wounds were 5cm² before starting controlled treatment (range 1-80cm²) and had been open for 7 months (range 2-48 months); the non-healing wounds were on average 11.2cm² (range 1-31cm²) and had been open for 26 months (range 8-106 months). Venous disease severity scores were similar for both groups (12.6 vs. 13.4). Five patients (18%) with healed ulcers regularly used walking aids, the use of which was more frequent (36%) among non-healers (p<0.001). Venous reflux profiles differed significantly between the groups, with isolated superficial reflux noted in 64% of healers, compared with 36% of non-healers. In addition, isolated deep reflux was found in 14% of the healers, compared with 41% of non-healers (p=0.0002). The rate of popliteal reflux was significantly higher in non-healers (59% versus 21%; p=0.0004). CONCLUSION: Long duration of a chronic venous ulcer may predict a poor outcome. The presence of deep venous reflux, especially in the popliteal vein, is typically found in those legs with non-healed ulcers. .

Predictors for the immediate and long-term outcome of a vascular surgical procedure.

BACKGROUND AND AIMS: The ability to predict post-operative mortality reliably will be of assistance in making decisions concerning the treatment of an individual patient. The aim of this study was to test the GAS score as a predictor of post-operative mortality in vascular surgical patients. MATERIAL AND METHODS: A total of 157 consecutive patients who underwent an elective vascular surgical procedure were included in the study. The Cox proportional hazards model was used in analyzing the importance of various preoperative risk factors for the postoperative outcome. ASA and GAS were tested in predicting the short and longterm outcome. On the basis of the GAS cut-off value 77, patients were selected into low-risk (GAS low: GAS<77) and high-risk (GAS high: GAS>or=77) groups, and the examined risk factors were analyzed to determine which of them had predictive value for the prognosis. RESULTS: None of the patients in the GAS low group died, and mortality in the GAS high group was 4.8% (p=0.03) at 30 days follow-up. The 12-month survival rates were 98.6% and 78.6% (p=0.0001), respectively, with the respective 5-year survival rates of 76.7% and 44.0% (p=0.0001). The only independent risk factor for 30-day mortality was the renal risk factor (OR 20.2). The combination of all three GAS variables (chronic renal failure, cardiac disease and cerebrovascular disease), excluding age, was associated with a 100% two-year mortality. CONCLUSIONS: Mortality is low for patients with GAS<77. For the high-risk patients (GAS>or=77), due to its low predictive value for death, GAS yields limited value in clinical practice. In cases of patients with all three risk factors (renal, cardiac and cerebrovascular), vascular surgery should be considered very carefully.

Prevalence and risk factors of PAD among patients with elevated ABI.

OBJECTIVES: To assess the prevalence and clinical significance of elevated ankle-brachial index (ABI) in patients referred to vascular consultation. DESIGN: Retrospective clinical study. MATERIAL AND METHODS: In 1,762 patients referred with a suspicion of peripheral arterial disease (PAD), ABI and toe brachial index (TBI) were measured by photoplethysmography. ABI>/=1.3 was considered falsely elevated and TBI<0.60 was the diagnostic criterion for PAD. RESULTS: The prevalence of elevated ABI was 8.4% and that of PAD among these patients 62.2%. PAD was significantly more prevalent among subjects with severe symptoms (rest pain, ulcers or gangrene) than in those with intermittent claudication (83.8% and 45.3%, respectively, p<0.001). The risk of PAD diagnosis was ten-fold (OR 10.31, 95% CI 2.07-51.30) among those with chronic renal failure, five-fold among patients with a history of smoking (OR 5.63, 95% CI 1.22-26.00) and over three-fold (OR 3.44, 95% CI 1.46-8.12) among those with coronary heart disease. The specificities of elevated ABI threshold levels (1.3, 1.4 and 1.5) in identifying PAD were 86%, 94% and 96%, respectively, the sensitivities being 44%, 38% and 36%, respectively. CONCLUSIONS: The prevalence of elevated ABI in patients referred to vascular consultation is 8.4% and that of PAD among these 62.2%. PAD is significantly more probable among those with chronic renal failure, a history of smoking and coronary heart disease. Furthermore, the specificity of elevated ABI (>/=1.3) in recognizing PAD is good, whereas the sensitivity is only satisfactory.

Lower extremity isometric strength in children with juvenile idiopathic arthritis.

OBJECTIVE: The aim of this study was to measure lower extremity isometric strength in patients with juvenile idiopathic arthritis (JIA) and to evaluate the usefulness of an adjustable dynamometer chair in the clinical work. METHODS: Twenty-five children with JIA and 25 healthy, age-matched controls, aged 7-12 (mean age 10.1) were studied. The isometric maximal strength of knee and ankle muscles was measured on both sides using the dynamometer chair. Before and after the measurements the Children's Effort Rating Table (CERT) was used to assess physical effort and feelings of exertion during the measurements. RESULTS: In all the tested muscle groups, there was a trend towards lower muscle strength values in the patients with JIA but significant differences were found only in knee extension (at 80 degrees knee angle) on both sides and in ankle plantarflexion if both ankles had had arthritis. No difference was observed in perceived exertion between patients and controls, but both groups significantly sensed the exertion after the muscle strength measurement (mean exertion before, JIA/control 2.2/2.0, and after 5.9/5.8). CONCLUSION: Isometric muscle strength in children with JIA can be close to normal when the disease is not active. However, especially in knee extensors and ankle plantarflexors, muscle weakness may occur. From technical standpoint, an adjustable dynamometer chair can be used for assessment of isometric maximal strength in children with JIA.

Impact of endovascular treatment on clinical status and health-related quality of life.

BACKGROUND AND AIMS: Investigating the impact of percutaneous transluminal angioplasty (PTA) on clinical status and health related quality of life in patients with claudication and critical limb ischaemia (CLI). MATERIAL AND METHODS: 61 patients and 64 limbs underwent a primary PTA (30 claudication and 34 CLI cases). Clinical status was graded according to Ahn and Rutherford and ankle/brachial index (ABI). Quality of life was assessed using the Nottingham Health Profile (NHP) preoperatively, one month and one year after the procedure. Triplex scan evaluation of the treated arterial segment was carried out postoperatively and one year after the procedure. RESULTS: Claudication: 24/27 patients underwent one-year follow up, after which 20/24 had no claudication. In triplex evaluation 17 (63.0%) treated segments were open with 0-50% restenosis, 9 (33.3%) with 51-99% restenosis and one (3.7%) was occluded. CLI: 13/34 (38.2%) patients underwent one-year follow-up after which eight patients (61.5%) were asymptomatic and five (38.1%) had claudication. In triplex evaluation there was 0-50% restenosis in 6 (46.2%) segments treated with PTA and 51-99% restenosis in 7 (53.8%) segments. 21 (61.8%) patients did not conclude the one year follow up: 7 had died, 5 had undergone bypass surgery and 6 an amputation and 3 did not attend the follow-up up for unknown reasons. Quality of life: For CLI patients, improvement was observed in the domain of pain, which continued throughout the follow-up period. Among the claudicants, the domain of physical mobility was improved at one month's follow-up, but this effect disappeared during the following year and could not be seen at one the one- year follow-up. CONCLUSIONS: Technical success and one-year results in claudication are good, and the rate of complications is low. However, although PTA resulted in an immediate improvement in the quality of life, this effect was not seen in the long term. In critical limb ischemia there was a group of patients in whom PTA led to a significant benefit in terms of limb salvage and quality of life.

Ten-year outcomes after endovascular aneurysm repair (EVAR) and magnitude of additional procedures.

BACKGROUND AND AIMS: With any new technology complications are possible, and problems with first-generation aortic stentgrafts have been extensively reported. The longterm outcome of this patient population and the magnitude of additional secondary procedures are, however, less well covered. MATERIALS AND METHODS: Between February 1997 and November 1999, 48 patients (44 men and 4 women; mean age 70 years; range 54-85) with AAA (average 57mm, range 40-90mm) were treated with a Vanguard endoprosthesis. Stentgrafts were sized by CT and angiography-based measurements. Results were continuously assessed using contrast-enhanced CT before discharge, 1, 3, 6 and 12 months after the procedure and thereafter annually. Since 2001 plain abdominal X-rays have been performed annually. RESULTS: The technical implant success rate was 100%. Median follow-up was 91 months (range 7.6-120 months). None of the patients was lost during this period. Hospital mortality was 0%. There were 25 subsequent deaths (52%), the most common cause being coronary artery disease. There were ten late conversions to open surgical repair, including three emergency operations: two due to rupture and one to thrombosis. EVAR-related complications were encountered in 43 patients (90%): 12 primary endoleaks (all type II), 36 late endoleaks (16 type I, 2 type II and 18 type III), 22 migrations, 25 row separations, 20 thromboses, one endotension and 3 ruptures of the AAA. Secondary procedures were required in 39 patients (81%): 1 re-endografting by aortoiliac bifurcated graft and 3 with a uni-iliac graft; 33 limb graft repairs were performed and 19 infrarenal cuffs were placed. There were 4 late embolizations and 4 attempts, and 6 thrombolyses, four of which were successful. Further, 9 femoro-femoral crossover by-pass and 2 axillofemoral by-pass operations and 2 amputations were carried out during the follow-up. Only one patient was alive without complications. CONCLUSIONS: The impact of long-term follow-up of patients treated with the new technology was emphasized in this patient population. A careful surveillance protocol and active endovascular treatment of complications can yield acceptable results and low AAA rupture and aneurysm mortality rates, also with the first-generation endovascular graft. A new technology, however, may involve unpredictable problems which can magnify the workload and incur high costs over several years after the initial procedure.

Clinical and hemodynamical findings in legs with previous surgery of the great saphenous vein: role of the small saphenous vein.

AIM: To assess the role of small saphenous vein (SSV) reflux in patients with a long history of varicose disease and previous stripping of the great saphenous vein (GSV). METHODS: Consecutive patients with a history of GSV stripping 5-19 years earlier were enrolled in this prospective clinical study. A total of 101 legs of 75 consecutive patients fulfilled the study criteria: previous stripping of GSV from ankle to groin at least 5 years earlier, no history of thromboembolism and no previous surgery of deep veins or SSV. All patients were studied clinically using standardized classifications: clinical class, clinical disability score (CDS) and venous clinical scoring system (VCSS). Colour flow duplex imaging (CFDI) was used to assess reflux in deep and superficial veins. Details of prior surgery were evaluated. RESULTS: Overall, SSV reflux was noted in 28 (28%) of the legs, recurrent GSV (rGSV) in the thigh in 41 (41%), reflux in tributaries alone in 28 (28%) and a combination of SSV and rGSV reflux in 4 (3%). Segmental deep reflux was measured in 23 (23%) of the legs; the prevalence of deep reflux was significantly higher in complicated than in uncomplicated legs (12% versus 47%; P<0.05). Deep reflux was more frequently associated with SSV reflux than with rGSV reflux (50% versus 22%; P<0.05). The prevalence of SSV with or without deep reflux increased from 17% to 50% (P<0.05) when uncomplicated (C2-3) and complicated (C4-6) legs were compared. A similar increase was not seen in the legs with rGSV (39% versus 44%; P>0.05). SSV reflux without deep reflux was observed in 25% of the legs with complicated (C4-6) disease, whereas the prevalence of SSV reflux was low (9%) in uncomplicated (C2-3) legs. VCSS was higher in the legs with SSV reflux than in those with rGSV reflux. CDS scores tended to be higher in the SSV reflux group than in the legs with rGSV reflux or tributary reflux alone. After exclusion of deep reflux, the results remained at the same level. CONCLUSION: Small saphenous vein (SSV) reflux is common in legs with recurrent varicose veins and previous stripping of the GSV. SSV reflux alone is frequent in complicated legs, and SSV reflux is typically associated with segmental deep reflux. Clinical and hemodynamical findings stress the role of SSV reflux in this selected venous population.

Lower limb amputations: differences between the genders and long-term survival.

The purpose of the study was to evaluate possible differences between genders in amputation incidence, revascularization activity before and survival after amputation. This population-based study was carried out in a well-defined geographical area, where all vascular surgical consultations and reconstructions are performed in one university hospital. All amputations performed in the region during 1990 - 1999 were identified from the hospital central registers. According to patient's identity codes, the Cause of Death Registry of Statistics Finland provided death data. Amputation data were cross-linked with the local vascular registry using identity codes. Women were found to be 8 years older than men (p < 0.0001). Major amputations comprised 73.4% in males and 77.7% in females. The age-standardized amputation incidence among males was 338 and among females 226 (per 10(6) inhabitants/year) (p < 0.001). The most prominent difference was seen in amputations due to trauma, where the age-adjusted major amputation incidence was over three-fold among males compared to females. The proportion of patients who had undergone vascular procedure before amputation was 23% in both genders. Median survival after amputation was 943 days in men and 716 in women (p = 0.01). When the higher age of women was considered, there was no significant difference between the genders. Survival was poorer among diabetics in both genders and the difference was significant in males. The amputation incidence was found to be higher in men compared to women in all etiologic subgroups except malignant tumour. Almost one in 4 patients had undergone vascular surgical reconstruction before amputation in both genders. There was no significant difference between the genders in survival after amputation. Subjects with diabetes had a poorer survival after major amputation than those without diabetes.

Preoperative physical examination for primary vascular access--reliability in determining vessel quality.

BACKGROUND AND AIMS: The purpose of this prospective clinical study was to evaluate the reliability and adequacy of preoperative physical examination in determining the quality of vessels prior to primary vascular access procedure by performing peroperative completion fistulography. MATERIAL AND METHODS: 26 consecutive patients who were scheduled for primary vascular access surgery, between July 2001 and June 2002, were included. Findings between the preoperative physical examination and peroperative completion fistulography were compared. RESULTS: Of the 26 patients that were initially enrolled in the study, 4 patients were excluded because physical examination showed poor superficial arm veins and 2 patients had not undergone access procedure by the end of the study. The remaining twenty patients constituted the actual study group. The arteriovenous fistula could be performed at the chosen level and way in all 20 patients. The findings between preoperative physical examination and peroperative fistulography were compatible and the specificity of physical examination to detect patent inflow and outflow vessels was 100%. Due to the fact that 4 patients in whom a poor vein was suspected were excluded, the sensitivity could not be assessed. CONCLUSIONS: Preoperative physical examination seems to be reliable and adequate method in determining vessel quality prior primary vascular access surgery. According to our study, its specificity is high in determining patent inflow and out-flow vessels. However, because of exclusion of patients with suspected problem, sensitivity cannot be determined.

Kallidin- and bradykinin-degrading pathways in human heart: degradation of kallidin by aminopeptidase M-like activity and bradykinin by neutral endopeptidase.

BACKGROUND: Since kinins kallidin (KD) and bradykinin (BK) appear to have cardioprotective effects ranging from improved hemodynamics to antiproliferative effects, inhibition of kinin-degrading enzymes should potentiate such effects. Indeed, it is believed that this mechanism is partly responsible for the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors. In the heart, enzymes other than ACE may contribute to local degradation of kinins. The purpose of this study was to investigate which enzymes are responsible for the degradation of KD and BK in human heart tissue. METHODS AND RESULTS: Cardiac membranes were prepared from the left ventricles of normal (n=5) and failing (n=10) hearts. The patients had end-stage congestive heart failure as the result of coronary heart disease or idiopathic dilated cardiomyopathy. Heart tissue was incubated with KD or BK in the presence or absence of enzyme inhibitors. We found no difference in the enzymes responsible for kinin metabolism or their activities between normal and failing hearts. Thus KD was mostly converted into BK by the aminopeptidase M-like activity. When BK was used as substrate, it was converted into an inactive metabolite BK-(1-7) mostly (80% to 90%) by the neutral endopeptidase (NEP) activity, with ACE unexpectedly playing only a minor role. The low enzymatic activity of ACE in the cardiac membranes, compared with that of NEP, was not due to chronic ACE inhibitor therapy, because the cardiac ACE activities of patients, whether receiving ACE inhibitors or not, and of normal subjects were all equal. CONCLUSIONS: The present in vitro study shows that in human cardiac membranes, the most critical step in kinin metabolism, that is, inactivation of BK, appears to be mediated mostly by NEP. This observation suggests a role for NEP in the local control of BK concentration in heart tissue. Thus inhibition of cardiac NEP activity could be cardioprotective by elevating the local concentration of BK in the heart.

The profile of leg symptoms, clinical disability and reflux in legs with previously operated varicose disease.

PURPOSE: It is difficult to assess the severity and location of venous insufficiency in legs with recurrent varicose disease. This present purpose was to evaluate the distribution of reflux and the diagnostic role of current classifications in a consecutive series of legs with previously operated varicose disease. METHODS: A total of 90 legs in a cohort of 66 patients were included. The examination comprised CEAP clinical class, clinical disability score (CDS) and leg symptoms. Colour-flow duplex imaging (CFDI) was used to observe reflux in deep and superficial veins. Details of prior surgery were assessed. RESULTS: The site of superficial reflux was at the groin in 58% (recurrent or residive vein trunk or unoperated great saphenous vein), and the rate in the popliteal fossa was 11% (unoperated short saphenous vein). In 58% of the legs presenting superficial reflux at groin level, previous surgery at the saphenofemoral junction was noted. A sensation of pain was observed in 74% of the legs, sensation of oedema in 64%, itching in 26 %, and night cramps in 8%, respectively. Only itching was significantly infrequent in uncomplicated (CEAP C 2-3) legs, and in legs with local reflux was restricted to vein tributaries. Higher CDS (classes 2-3) were significantly more frequent among complicated legs (CEAP clinical class C2-3: 22% versus CEAP clinical class C4-6: 77%; p < 0.005). A similar situation was noted when legs with only local reflux were compared to those with more severe reflux (local reflux: 7% versus severe reflux: 48%; p < 0.005). CONCLUSIONS: Superficial reflux is frequently detected at groin level despite prior surgery. Unstructured evaluation of leg symptoms is not beneficial. Clinical disability scores associate well with the severity of the venous disease.

Purified HrpA of Pseudomonas syringae pv. tomato DC3000 reassembles into pili.

Pseudomonas syringae pv. tomato DC3000 produces Hrp pili under inducing in vitro conditions. A preparation of partially purified extracellular filaments contains HrpA, flagellin and some minor contaminants. HrpA was separated from the major contaminant, the flagellin, by gel filtration to a fraction containing HrpA as well as its three N-terminally truncated forms. These were further separated by two steps of reversed phase chromatography. HrpA and its degradation products were each shown to reassemble into filament structures after denaturation and renaturation showing that HrpA alone is sufficient for formation of filament structures.

Activation of interstitial collagenase, MMP-1, by Staphylococcus aureus cells having surface-bound plasmin: a novel role of plasminogen receptors of bacteria.

Plasmin, the enzymatically active form of plasminogen, can activate several matrix metalloproteinases (MMPs). In this study, we investigated the activation of MMP-1, one of the major interstitial collagenases, by plasmin which was generated on the surface of Staphylococcus aureus cells. Plasmin bound to plasminogen receptors on S. aureus degraded the major (125)I-labeled 55-kDa proMMP-1 into the 42-kDa form corresponding to the size of active MMP-1. MMP-1 formed by S. aureus-bound plasmin was also enzymatically active as judged by digestion of the synthetic collagenase substrate, DNP-Pro-Leu-Gly-Leu-Trp-Ala-D-Arg-NH(2). The finding that, in MMP-1 molecules generated either by soluble plasmin or by S. aureus-bound plasmin, the amino-terminal amino acid sequences were identical indicated that the activation mechanisms of the two plasmin forms do not differ from each other. The present observations emphasise and broaden the physiological importance of bacterial plasminogen receptors. In addition to direct proteolytic effects on components of the extracellular matrix, receptor-bound plasmin is also capable of initiating an MMP-1-dependent matrix-degrading enzymatic cascade.

A novel function for a ubiquitous plant enzyme pectin methylesterase: the host-cell receptor for the tobacco mosaic virus movement protein.

Plant virus-encoded movement proteins promote viral spread between plant cells via plasmodesmata. The movement is assumed to require a plasmodesmata targeting signal to interact with still unidentified host factors presumably located on plasmodesmata and cell walls. The present work indicates that a ubiquitous cell wall-associated plant enzyme pectin methylesterase of Nicotiana tabacum L. specifically binds to the movement protein encoded by tobacco mosaic virus. We also show that pectin methylesterase is an RNA binding protein. These data suggest that pectin methylesterase is a host cell receptor involved in cell-to-cell movement of tobacco mosaic virus.

Analysis of spatial structure in eccentric vision.

The analysis of spatial structure, ie, the encoding of relative positions between pattern elements, was studied in central and eccentric vision. In a two-alternative forced-choice task the observer had to discriminate between two patterns consisting of short line segments. At each trial the two patterns were flashed for 140 msec and the observer indicated whether the patterns were identical or mirror symmetric. Psychometric functions were measured by changing pattern size at each eccentricity in order to find the threshold size allowing 75% of correct responses. The scaling factor, required for discriminating between mirror symmetric and identical patterns independent of eccentricity, was found to be similar to the size-scaling proposed by Levi et al (Vision Res 25:963, 1985) for vernier acuity tasks.