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Chinese and American children aged 5-11 years (total N = 144) heard two child informants make conflicting empirical claims about each of 4 scenarios. For example, one informant claimed that a ball would float when dropped in water whereas the other informant claimed that it would sink. Children were asked to judge whether each informant could be right, and to justify their overall judgment. In both samples, there was a change with age. Older children often said that each informant could be right whereas younger children, especially in China, were more likely to say that only one informant could be right. Nevertheless, in the wake of decisive empirical evidence (e.g., the ball was shown to sink when dropped in water), almost all children, irrespective of age, drew appropriate conclusions about which of the two informants had been right. Thus, with increasing age, children differ in their prospective - but not in their retrospective - appraisal of empirical disagreement. Absent decisive evidence, older children are more likely than younger children to suspend judgment by acknowledging that either of two conflicting claims could be right. We argue that children's tendency to suspend judgment is linked to their developing awareness of empirical uncertainty, as expressed both in the justifications they give when judging the disagreement and in their own beliefs about the scenarios. Implications for children's understanding of disagreement are discussed., Competing Interests: Declaration of Competing Interest We have no conflicts of interests to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Across cultures, studies report more confidence in the existence of unobservable scientific phenomena, such as germs, as compared to unobservable religious phenomena, such as angels. We investigated a potential cultural mechanism for the transmission of confidence in the existence of invisible entities. Specifically, we asked whether parents in societies with markedly different religious profiles-Iran and China-signal differential confidence across the domains of science and religion during unmoderated conversations with their children (N = 120 parent-child dyads in total; 5- to 11-year-olds). The results revealed that parents used fewer lexical cues to uncertainty when discussing scientific phenomena, as compared to religious phenomena. Unsurprisingly, this cross-domain distinction was observed among majority belief, secular parents in China (Study 2). More importantly, however, the same pattern was observed among parents in Iran, a highly religious society (Study 1), as well as among minority belief, religious parents in China (Study 2). Thus, adults in markedly different belief communities spontaneously express less confidence in religious, as compared to scientific, invisible entities in naturalistic conversation. These findings contribute to theories on the role of culture and testimony in the development of beliefs about unobservable phenomena., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Within the domains of both science and religion, beliefs in unobservable phenomena - such as bacteria or the soul - are common. Yet given the radically different trajectory of scientific as compared to religious beliefs across human history, it is plausible that the psychological basis for beliefs in these two domains is also different. Indeed, there is evidence from children and adults in various cultures that people have greater confidence in their scientific beliefs than in their religious beliefs. However, when individuals are invited to indicate the basis for their beliefs within each domain, a surprisingly similar pattern of justification is apparent., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Children hold beliefs about religious and scientific entities, such as angels or germs, that they cannot directly observe or interact with. Given their limited opportunities for first-hand observation, children's beliefs in these entities are a clear example of cultural learning and are likely to vary based on cultural factors. In the present study, we investigated variation in the epistemic stance of 4-11-year-old children growing up in a religious minority in China (N = 47), a religious majority in Iran (N = 85), and a religious majority in the U.S. (N = 74). To assess the role of community status as a domain-specific, as opposed to a domain-general, factor contributing to children's beliefs about unobservable entities, we compared children's beliefs about religious unobservable entities with their beliefs about scientific unobservable entities in these three communities. In all three communities, younger and older children were confident that unobservable religious and scientific entities exist. However, compared to children in Iran and the U.S., children from the religious minority group in China were more likely to justify their ontological beliefs about religious entities by appealing to the source of their beliefs. These results highlight the impact of community status on learning from testimony about unobservable entities. Additionally, the results show that under certain circumstances - notably when holding minority beliefs - tracking the source of beliefs serves as a central epistemic justification., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Children ranging from 4 to 8years (n=39) reported whether they could imagine various improbable phenomena (e.g., a person making onion juice) as well as various impossible phenomena (e.g., a person turning an onion into a banana) and then described what they imagined. In their descriptions, children mentioned ordinary causes much more often than extraordinary causes. Descriptions of such ordinary causes were provided more often in relation to improbable (rather than impossible) phenomena. Following these imaginative efforts, children judged if each phenomenon could really happen. To check whether these reality judgments were affected by children's attempts to imagine, a control group (n=39) made identical reality judgments but were not first prompted to imagine each phenomenon. Children across the age range judged that impossible phenomena cannot really happen but, with increasing age, judged that improbable phenomena can happen. This pattern emerged in both the imagination and control groups; thus simply prompting children to imagine did not alter their reality judgments. However, within the imagination group, judgments that phenomena can really happen were associated with children's claims to have successfully imagined the phenomena and with certain characteristics of their descriptions: imagining ordinary causes and imagining phenomena obtain. Results highlight close links between imagination and reality judgments in childhood. Contrary to the notion that young children have a rich imagination that readily defies reality, results indicate that their imagination is grounded in reality, as are their beliefs., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Theory-of-mind (ToM) refers to knowledge and awareness of mental states in oneself and others. Various training programs have been developed to improve ToM in children., Objectives: In the present study, we conducted a quantitative review of ToM training programs that have been tested in controlled studies., Data Sources: A literature search was conducted using PubMed, PsycInfo, the Cochrane Library, and manual searches., Review Methods: We identified 32 papers with 45 studies or experiments that included 1529 children with an average age of 63 months (SD=28.7)., Results: ToM training procedures were more effective than control procedures and their aggregate effect size was moderately strong (Hedges' g=0.75, CI=0.60-0.89, p<.001). Moderator analyses revealed that although ToM training programs were generally effective, ToM skill-related outcomes increased with length of training sessions and were significantly higher in active control studies., Conclusion: ToM training procedures can effectively enhance ToM in children., (Copyright © 2016 Elsevier B.V. All rights reserved.)

What kinds of cues increase imitative fidelity in early childhood? The effects of multiple models and verbal framing were examined in preschool children (N = 259, 3-6-year-olds). Each participant was presented with one of eight possible combinations of type of modeling and verbal frame. The type of modeling involved: (i) a single model offering two demonstrations, (ii) two successive models each offering a single demonstration, (iii) two synchronous models each offering two demonstrations, or (iv) two synchronous models each offering a single demonstration. The verbal frame preceding the demonstrations emphasized either the instrumental outcome of the actions or their conventionality. Imitative fidelity was highest for the synchronous models (types iii and iv) and lowest for the single model (type i). Imitative fidelity was also higher for the convention-oriented than the outcome-oriented frame and higher for older than younger children. Children also provided more conventional explanations for their actions after viewing the synchronous models and after the convention-oriented framing. The results indicate that children's imitative fidelity depends on the number of actors and the way the actions are framed., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Spinal cord ischemia (SCI) is a catastrophic complication of thoracoabdominal aortic aneurysm (TAAA) repair. This article describes our early experience with a technique for maintaining perfusion of segmental vessels (intercostals and lumbars) in the early postoperative period after endovascular repair of a TAAA, with "sac perfusion branches" added to custom-made stent grafts. These are closed 7 to 10 days after the first procedure to complete exclusion of the aneurysm. We have used this technique in 10 patients with type II TAAAs. One developed monoparesis of the right leg during a period of hypotension secondary to a cardiac event and died within 30 days. Two patients developed lower limb weakness after closure of the perfusion branches, both with full recovery. Controlled perfusion of segmental vessels with perfusion branches is feasible and may be a useful adjunct to prevent SCI, providing protection to spinal cord perfusion during the immediate postoperative period when risk of SCI is greatest., (Crown Copyright © 2012. Published by Mosby, Inc. All rights reserved.)

The treatment of chronic type B aortic dissections remains challenging and controversial. Currently most centers advocate open or endovascular intervention for patients with evidence of malperfusion, rupture or impending rupture, continued pain, or aneurysm formation. Regardless of the type of intervention, the incidence of complications or death remains high, even when undertaken in an elective setting. The standard endovascular treatment usually involves placement of a stent graft into the true lumen of the dissection in an effort to exclude the false lumen. This case report describes the placement of a branched stent graft into the false lumen of a patient with chronic type B dissection to encourage exclusion and thrombosis of the true lumen whilst maintaining flow to all visceral vessels., (Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: The outcomes for patients after endovascular treatment of abdominal aortic aneurysm (AAA) are determined primarily by the endpoints of death and endoleaks, the latter representing continued risk of rupture. The data of a multicentre registry were analysed with regard to the early outcome of stent-graft procedures for AAA and the complications associated with this treatment. In addition, the results during follow-up were analysed by determining mortality and endoleak development as separate endpoints and as a combined endpoint defined as endoleak-free survival., Setting: 38 European institutions of Vascular Surgery collaborating in a multicentre registry project., Patients and Methods: 899 patients with AAA underwent between May 1994 and March 1998 elective endovascular repair (818 men and 81 women; mean age 69 years). 80 (8.9%) of the patients had medical conditions that excluded them from open repair. 818 (91%) of patients had a bifurcated device, 63 (7%) had a straight tube graft, and only 18 (2%) had an aorto-uni-iliac device. Clinical examination and contrast-enhanced computed tomography was performed at fixed follow-up intervals to assess increase or decrease of the maximum transverse diameter (MTD). Endoleaks observed at follow-up were discriminated into persistent endoleak and temporary endoleak. The latter is defined as single time observed endoleaks or with two or more negative imaging studies between observed endoleaks. Life-table analyses were used to calculate the rates of freedom-from-endoleak (no endoleak at any time), freedom-from-persistent endoleak (no persistent endoleak), patient survival, and persistent-endoleak-free-survival., Results: The median follow-up of this patient series was 6.2 months. The ratio between observed and expected follow-up data was 82% for the overall follow-up period. However, at 18 months of follow-up this rate was only 45%. The number of patients followed during this period was sufficient to allow statistically meaningful assessment. The MTD in patients with temporary endoleaks demonstrated a significant decrease at 6 to 12 months compared to preoperative values (mean 57 and 53 respectively, p = 0.004). In patients with persistent endoleaks there was no change between the preoperative and 6-month MTD (mean 57 and 60 mm respectively). At 6 and 18 months freedom-from-endoleak was 83% and 74% and freedom-from-persistent endoleak was 93% and 90%, respectively. The 18-month cumulative patient survival was 88% and the main outcome measure, the persistent endoleak-free-survival was 79%., Conclusions: The MTD decreases in patients with temporary endoleak, but not in patients with persistent endoleak. Therefore, the use of the rate of freedom-from-persistent endoleak, reflecting absence of persisting endoleaks to estimate the prognosis with regard to the AAA, is justified. Determining persistent endoleak-free survival appears a rational approach to provide a realistic outlook for patients with stent-grafted AAA. The observed 18-month endoleak-free survival reflects a satisfactory mid-term result., (Copyright © 2011. Published by Elsevier Ltd.)

Prolonged endovascular procedures requiring a large diameter sheath in each groin can be associated with significant intraoperative lower limb ischemia, particularly in those with pre-existing peripheral vascular disease. We report the case of a patient who suffered severe ischemia-reperfusion injury following endovascular repair of a pararenal aortic aneurysm using a fenestrated stent graft and describe the use of temporary axillobifemoral bypass in a patient with similar comorbidities undergoing the same procedure. We propose this adjunctive technique as a means of maintaining antegrade limb perfusion and avoiding the peripheral and central metabolic consequences of ischemia-reperfusion injury., (Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

In situ fenestration of aortic stent grafts has the potential to allow for continued perfusion of supra-aortic trunks, without the need for extra-anatomic bypass, and without the need for custom-made devices. Angulation of the target vessel relative to the arch is an obstacle to success with this technique. In this report, we describe a case of successful in situ fenestration of the left subclavian artery (LSA) in a patient with an aortic arch aneurysm, treated with an endovascular stent graft. We outline a novel technique using through and through wire access and a pre-curved semi-rigid sheath, which allows successful access to the lumen of the aortic stent graft, despite an acute angle at the take-off of the LSA., (Copyright (c) 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: A prototype ready-to-fenestrate stent graft (RFSG) was designed with a fixed scallop, and eight potential fenestrations allowing for variation in the position of each renal artery (RA) relative to the superior mesenteric artery (SMA). We aimed to determine the proportion of juxtarenal aneurysms treatable using this potentially 'off-the-shelf' device., Methods: A total of 439 consecutive orders for custom-made devices were analysed, and positions for potential fenestrations in the RFSG were determined, based on the most frequent anatomical target vessel variations: a fixed SMA scallop 12 mm deep at 12:00, RA fenestrations at 9:15, 10:15 (target within the range 8:45-10:45), 2:15 and 3:15 (target within the range 1:45-3:45), each either 19 or 28 mm from the graft edge (GE); (within the range 15-32 mm), and 6 x 8 mm in diameter. Proximal diameters of 24, 26, 28, 30, 32 and 36 mm were chosen., Results: Of the 439 plans, 372 standard juxtarenal (SJR) cases, defined by the inclusion of a scallop and 0, 1 or 2 small fenestrations (12%, 13% and 75% of the cases, respectively) were identified and used to test the applicability of the model. Mean CP (clock position) for right RA was 9:30, for the left RA 3:00, being a mean of 21 +/- 5 and 22 +/- 5 mm, respectively from the GE. RA CP was within the RFSG range in 86% (right) and 88% (left) of the cases, with 96% and 98%, respectively, within the allowable distance from the GE. A total of 81% of all SJR cases were potentially treatable using the RFSG model., Conclusions: An RFSG device would allow for the treatment of the majority of juxtarenal aortic aneurysms, which currently require custom-made devices.

Based on the testimony of others, children learn about a variety of figures that they never meet. We ask when and how they are able to differentiate between the historical figures that they learn about (e.g., Abraham Lincoln) and fantasy characters (e.g., Harry Potter). Experiment 1 showed that both younger (3- and 4-year-olds) and older children (5-, 6-, and 7-year-olds) understand the status of familiar figures, correctly judging historical figures to be real and fictional figures to be pretend. However, when presented with information about novel figures embedded in either a realistic narrative or a narrative with obvious fantasy elements, only older children used the narrative to make an appropriate assessment of the status of the protagonist. In Experiment 2, 3-, and 4-year-olds were prompted to judge whether the story events were really possible or not. Those who did so accurately were able to deploy that judgment to correctly assess the status of the protagonist.

Objective: Endovascular treatment of thoracic aortic disease may be associated with severe neurologic complications. The current study used the data of a multicenter registry to assess of the incidence and the risk factors for paraplegia or paraparesis and intracranial stroke., Methods: The European Collaborators on Stent/Graft Techniques for Aortic Aneurysm Repair (EUROSTAR) database prospectively enrolled 606 patients. Thoracic pathologies with urgent or elective presentation, which included degenerative aneurysm in 291, aortic dissection in 215, traumatic rupture in 67, anastomotic false aneurysm in 24, and infectious or nonspecified disorders in 9. Study end points included evidence of perioperative spinal cord ischemia (SCI) or stroke. Univariate analysis and multivariate regression models were used to assess the significance of clinical factors that potentially influenced the occurrence of neurological sequelae., Results: Paraplegia or paraparesis developed in 15 patients (2.5%) and stroke in 19 (3.1%); two patients had both complications. At multivariate regression analysis, independent correlation with SCI was observed for four factors: (1) left subclavian artery covering without revascularization (odds ratio [OR], 3.9; P = .027), (2) renal failure (OR, 3.6; P = .02), (3) concomitant open abdominal aorta surgery (OR, 5.5; P = .037) and (4) three or more stent grafts used (OR, 3.5; P = .043). In patients with perioperative stroke, two correlating factors were identified: (1) duration of the intervention (OR, 6.4; P = .0045) and (2) female sex (OR, 3.3; P = .023). A neurologic complication (paraplegia or stroke) developed in 8.4% of the patients in whom left subclavian covering was required compared with 0% of patients with prophylactic revascularization (P = .049)., Conclusion: Perioperative paraplegia or paraparesis was significantly associated with blockage of the left subclavian artery without revascularization. The clinical significance of this source of collateral perfusion of the spinal cord had not been confirmed previously. Intracranial stroke was associated with lengthy manipulation of wires, catheters, and introducer sheaths within the aortic arch, reflected by a longer duration of the procedure.

Alzheimer disease and cerebrovascular dementia are two common causes of dementia and, by present diagnostic criteria, are mutually exclusive using vascular pathology as an arbitrary demarcation in differential diagnosis. However, evidence from epidemiological, neuropathological, clinical, pharmacological, and functional studies suggest considerable overlap in risk factors and pathological changes suggesting shared common pathogenic mechanisms between these two diseases such that vascular factors play a vital role in the pathogenesis of Alzheimer disease. A high energy demand and lack of an endogenous fuel reserve make the brain highly dependent upon a continuous blood supply where disruption of cerebral blood vessels and blood flow can have serious consequences on neural activities. Indeed, many studies implicate metabolic defects in Alzheimer disease, such a reduced brain metabolism is one of the best documented abnormalities in the disease. Notably, since endothelial reactive oxygen species such as nitric oxide act as vasodilators at low concentrations, increased production coupled with elevated reactive oxygen species scavenging of nitric oxide, can lead to reduced bioavailability of nitric oxide and increased oxidative stress that damage sensitive vascular cells. In this respect, we and others have demonstrated that oxidative stress is one of the earliest pathological changes in the brain of Alzheimer disease patients and plays a critical role in the vascular abnormalities underlying metabolic defects in Alzheimer disease. Here, we discuss vascular factors in relation to Alzheimer disease and review hypoperfusion as a potential cause by triggering mitochondrial dysfunction and increased oxidative stress initiating the pathogenic process.

Background: Patients with abdominal aortic aneurysm (AAA) can be treated by transfemoral endovascular intervention and by conventional open surgery. Level-one evidence of the safety and efficacy of one treatment mode over the other is only provided by a randomised controlled trial (RCT). Results reported by voluntary registries are considered less valid than data from RCTs. On the other hand the outcome of a RCT may not be generalisable to the common practice because of vigorous selection of patients and institutions., Purpose: The outcomes reported by the Dutch Randomized Endovascular Aneurysm Management (DREAM) trial were compared with the results of the EURopean collaborators on Stent-graft techniques for AAA Repair (EUROSTAR) registry., Methods: To obtain comparable study groups with regard to risk factors equal proportions of ASA I, II and III patients as observed in the endovascular arm of the DREAMtrial were selected at random from the EUROSTAR-registry. All patients had an aneurysm of at least 50mm. Only patients, who had been enrolled into the registry from 1999, were selected to avoid the influence of first generation endografts which are not longer in use. Patient characteristics and outcomes of endovascular AAA repair (EVAR) of EUROSTAR and DREAM-trial participants were compared. Differences in early findings between study groups were assessed by Chi-Square tests for discrete variables and by Wilcoxon rank sum tests for continuous variables. Follow-up variables were analysed by Kaplan-Meier and Cox proportional hazard models., Results: Data of 177 patients of the DREAM trial with randomization to EVAR and 856 patients selected in the EUROSTAR-registry were compared. Baseline characteristics were comparable between the EUROSTAR-cohort and EVAR-arm of the DREAM-trial. The 36-month survival-rate was 87.6% for EVAR-arm in the DREAM-trial similar to the 86.8% found in this EUROSTAR-study population. The freedom of secondary procedures reached after 3 years 85.7%, and 86.9% in the DREAM and EUROSTAR-cohort, respectively., Conclusion: We found comparable characteristics and outcomes between patients of comparable risk class of the EUROSTAR-registry and the EVAR-cohort of the DREAM-trial. This demonstrates the following: first, the EUROSTAR-data provide reliable information, and further comparisons of registry data with patients treated by conventional AAA surgery may be justified. Secondly, the various outcomes of the randomised DREAM trial appear generalisable, as it agrees with observations in a broad common practice derived database.

Objectives: To examine the risk of high-flow type II endoleak following endovascular repair of abdominal aortic aneurysm with aortocaval fistula., Design: Case reports., Subjects: Two patients with abdominal aortic aneurysms with aortocaval fistula., Methods: Both patients had an endovascular repair of their aortic aneurysms., Results: The aneurysms were successfully treated in both patients, without any endoleak on completion angiography. Apart from a transient type II lumbar endoleak in one of the patients, no endoleak was found after 3 and 12 month follow-up. Seven other cases have been published, reporting one type II and one type Ic endoleak., Conclusion: We found no evidence that endovascular repair of abdominal aortic aneurysm with aortocaval fistula is associated with a higher incidence of persistent endoleak.

Objective: There is still debate whether type II endoleaks represent a risk for the patient after EVAR. Treatment policies vary from fairly conservative to active intervention. In this analysis risk factors for type II endoleak and adverse events during follow-up were assessed. In addition, risk factors and causes for conversion to open repair and for rupture post-EVAR were studied., Methods: The data of 3595 patients, who underwent operation between 1996 and 2002 in 114 European institutions that collaborated in the EUROSTAR Registry, were assessed. To accurately assess the influence of type II endoleaks patients with type I, III and combined endoleaks were excluded from the present study cohort., Results: A combined adverse outcome event consisting of aneurysmal growth, transfemoral reintervention, and transabdominal secondary procedures (including laparoscopic branch vessel clipping) occurred in 55% in patients with type II endoleak at 3 years, compared to 15% in patients without any endoleak (p<0.0001). Conversion to open repair or post-EVAR rupture was not significantly associated with type II endoleaks. An independent association of device migration and expansion of the aneurysm with late conversion was observed. The cumulative incidence of aneurysm rupture at 3 years of follow-up was 1.2% for an annual rate of 0.4%. Variables that significantly and independently correlated with rupture were size of the aneurysm at preoperative measurement and device migration during follow-up., Conclusion: Endoleak type II may not be harmless as it was more frequently associated with enlargement of the aneurysm and reinterventions. Large aneurysms and migration of the device were the main risk factors for rupture. The clinical implications of these findings may involve more frequent surveillance visits for patients with type II endoleak. Aneurysm expansion is a clear indication for reintervention. Patients with large aneurysms, 65 mm or larger, may also benefit from a more comprehensive surveillance schedule.

Objectives: This study was undertaken to determine the effect of the preoperative diameter of abdominal aortic aneurysms on the midterm outcome after endovascular abdominal aneurysm repair (EVAR)., Method: The data for 4392 patients who had undergone EVAR were analyzed. Patients were enrolled over 6 years to June 2002 in the EUROSTAR database. Outcomes were compared between three groups defined by the preoperative diameter of the aneurysm: group A (n = 1962), 4.0 to 5.4 cm; group B (n = 1528), 5.5 to 6.4 cm; and group C (n = 902), 6.5 cm or larger. Patient characteristics, details of aortoiliac anatomy, operative procedures, old or current device generation, and postoperative complications in the three patient groups were compared. Outcome events included aneurysm-related death, unrelated death, conversion, and post-EVAR rupture of the aneurysm. Life table analysis and log-rank tests were used to compare outcome in the three study groups. Multivariate Cox models were used to determine whether baseline and follow-up variables were independently associated with adverse outcome events., Results: Patients in group C were significantly older than patients in groups A and B (73 years vs 70 and 72 years, respectively; P =.003 - P <.0001 for different group comparisons), and more frequently were at higher operative risk (American Society of Anesthesiologists classification >or=3; 63% vs 48% and 54%; P =.0002-P <.0001). Device-related (type I) endoleaks were more frequently observed at early postoperative arteriography in group C compared with groups A and B (9.9% vs 3.7% and 6.8%; P =.01-P <.0001). Postoperatively systemic complications were more frequently present in group C (17.4% vs 12.0% in group A and 12.6% in group B; P <.0001 and.001). The first-month mortality was approximately twice as high in group C compared with the other groups combined (4.1% vs 2.1%; P <.0001). Late rupture was most frequent in group C. Follow-up results at midterm were less favorable in groups C and B compared with group A (freedom from rupture, 90%, 98%, and 98% at 4 years in groups C, B, and A, respectively; P <.0001 for group C vs groups A and B). Aneurysm-related death was highest in group C (88% freedom at 4 years, compared with 95% in group B and 97% in A; P =.001 and P <.0001, respectively; group B vs A, P =.004). The annual rate of aneurysm-related death in group C was 1% in the first 3 years, but accelerated to 8.0% in the fourth year. Incidence of unrelated death also was higher in groups C and B than in group A (76% and 82% freedom at 4 years vs 87%; P <.0001 for both comparisons). Ratio of aneurysm-related to unrelated death was 23%, 21%, and 50% in groups A, B, and C, respectively. Cox models demonstrated that the correlation between large aneurysms (group C) and all assessed outcome events was independent and highly significant. Older generation devices had an independent association with aneurysm-related and unrelated deaths (P =.02 and P =.04, respectively). However, this correlation was less strong than large aneurysm diameter (P =.0001 and P =.0009, respectively)., Conclusions: The midterm outcome of large aneurysms after EVAR was associated with increased rates of aneurysm-related death, unrelated death, and rupture. Reports of EVAR should stratify their outcomes according to the diameter of the aneurysm. Large aneurysms need a more rigorous post-EVAR surveillance schedule than do smaller aneurysms. In small aneurysms EVAR was associated with excellent outcome. This finding may justify reappraisal of currently accepted management strategies.

Objectives: Although small, the risk of rupture after EVAR remains a major concern. The aim of this study was to identify mechanisms of late aneurysm rupture after endovascular repair., Methods: Patients who suffered a proven aneurysm rupture after EVAR were identified from the EUROSTAR (European Collaborators on Stent-graft Techniques for Abdominal Aortic Aneurysm Repair) registry. Complications preceding rupture were studied to identify common patterns and possible mechanisms of late rupture., Results: A rupture was documented in 34 patients resulting in death of 21 (62%). Adverse events documented during previous follow-up in these patients included endoleak (30%), migration (18%), limb occlusion (12%) and kinking (12%). The findings at time of rupture were documented in 24 patients and including endoleak: Type III (10), Type I (9), Type II (1); stent-graft disintegration (2) and migration (3). Aneurysm diameter changes could be ascertained in 24 patients and had increased in only seven., Conclusion: The importance of graft-related endoleak, stent-graft disintegration and migration in the causation of aneurysm rupture was confirmed. Poor compliance with follow-up schedule was also identified as a common feature. However, the absence of complications in some patients, who attended regularly for follow-up, highlights the difficulty of predicting rupture after EVAR.

Objective: to examine the effect of stent-graft deployment on pressure within an aneurysm sac and to investigate the potential sources of intra-sac pressure., Material and Methods: intra-sac pressure was monitored during and immediately after endovascular repair via an indwelling catheter. Intra-sac pressure was also monitored during conventional open repair and was compared with the pressure measured within patent lumbar and inferior mesenteric side-branches, both before and after restoration of iliac arterial blood flow. Intra-sac and side-branch pressures were recorded and expressed as ratios of simultaneously measured radial artery pressure., Results: in the absence of a graft-related endoleak (23/25 patients), endovascular repair resulted in a significant reduction in intra-sac pulse pressure (median ratio 0.31 IQR 0.10-0.46). There was no corresponding reduction in mean intra-sac pressure (median ratio 0.91; IQR 0.83-1.00). Application of clamps at conventional open repair resulted in a fall in both intra-sac pressure (median ratio 0.39, IQR 0.32-0.64) and pressure within side-branches (median ratio 0.45, IQR 0.33-0.64). Restoration of iliac blood flow resulted in a modest recovery of the side-branch pressure (median ratio 0.63, IQR 0.57-0.81), which nonetheless remained significantly less than the intra-sac pressure recorded after EVAR (p=0.01)., Conclusion: reperfusion of the aneurysm sac through patent side-branches seems insufficient to account for persistent pressurisation of the aneurysm after endovascular repair. This finding supports the hypothesis that pressure may be transmitted directly through stent-graft fabric.

Introduction: the rationale behind the Distaflo graft is inhibition of myointimal hyperplasia through optimisation of haemodynamic forces at the distal anastomosis. This prospective study reports our early clinical results., Method: patients with critical limb ischaemia, but no autologous vein, underwent infrainguinal bypass using Distaflo. Clinical and Duplex assessment provided prospective data from which one year cumulative patency, limb salvage and survival rates were calculated using Kaplan-Meier analysis. Log rank test enabled comparison with an historical control group of Miller cuff grafts., Results: fifty Distaflo were inserted over 29 months into 46 patients, median age 68.5 years, 27 male (59%), of which 27 (54%) were re-do procedures. Proximal anastomoses were to common femoral arteries in 40 cases (80%); distal anastomoses were to popliteal vessels in 20 (40%), and tibial vessels in 30 (60%). The Distaflo graft had patency, limb salvage and survival rates of 39, 50 and 82% respectively compared to 49, 56 and 85% respectively in the control group, with no statistical difference (p = 0.39; 0.65; 0.67 respectively; log rank)., Conclusion: in this non-randomised study, the Distaflo has similar one year patency, limb salvage and survival rates to the Miller cuff, potentially justifying its use an alternative in distal prosthetic arterial reconstruction for critical limb ischaemia.

Objective: To determine whether the experience of the specialist team was associated with adverse events following endovascular treatment of abdominal aortic aneurysms., Methods: The EUROSTAR database is a voluntary registry of 2863 patients admitted to 93 hospitals in Europe with an abdominal aortic aneurysm treated with endovascular stenting. Mortality, rupture and the need for secondary interventions were the main outcomes., Results: In patients who underwent endovascular stenting by the most experienced specialist teams the mortality rate was 40% lower than in those treated by the least experienced teams (adjusted hazard ratio 0.60, 95% confidence interval: 0.4-1.0; p = 0.05). Also patients treated by the most experienced specialist teams were 68% less likely to have adverse events necessitating a secondary intervention than those treated by the least experienced teams (adjusted hazard ratio 0.32, 95% confidence interval: 0.2-0.5; p < 0.001). The crude rupture rate was 0.1% among patients treated by the most experienced specialist teams and 0.8% among those treated by the least experienced teams (p = 0.74)., Conclusions: Specialist teams with a high level of experience of endovascular abdominal aortic aneurysm stenting encounter lower mortality rates and fewer adverse events leading to secondary interventions.

Objective: Endoleaks and endotension are critically important complications of some endovascular aortic aneurysm repairs (EVARs). For the resolution of controversial issues and the determination of areas of uncertainty relating to these complications, a conference of 27 interested leaders was held on November 20, 2000., Methods: These 27 participants (21 vascular surgeons, five interventional radiologists, one cardiologist) had previously answered 40 key questions on endoleaks and endotension. At the conference, these 40 questions and participant answers were discussed and in some cases modified to determine points of agreement (consensus), near consensus (prevailing opinion), or disagreement., Results: Conference discussion added two modified questions for a total of 42 key questions for the participants. Interestingly, consensus was reached on the answers to 24 of 42 or 57% of the questions, and near consensus was reached on 14 of 42 or 33% of the questions. Only with the answers to four of 42 or 10% of the questions was there persistent controversy or disagreement., Conclusion: The current endoleak classification system with some important modifications is adequate. Types I and II endoleak occur after 0 to 10% and 10% to 25% of EVARs, respectively. Many (30% to 100%) type II endoleaks will seal and have no detrimental effect, which never or rarely occurs with type I endoleaks. Not all endoleaks can be visualized with any technique, and increased pressure (endotension) can be transmitted through clot. Aneurysm pulsatility after EVAR correlates poorly with endoleaks and endotension. An enlarging aneurysm after EVAR mandates surgical or interventional treatment. These and other conclusions will help to resolve controversy and aid in the management of these vexing complications and should also point the way to future research in this field.

Objective: The purpose of this study was to assess the incidence, risk factors, and consequences of endoleaks after endovascular repair of abdominal aortic aneurysm., Methods: Data on 2463 patients were collected from 87 European centers and recorded in a central database. Preoperative data were compared for patients with collateral retrograde perfusion (type II) endoleak (group A), patients with device-related (type I and III) endoleaks (group B), and patients in whom no endoleak was detected (group C). Only endoleaks observed after the first postoperative month of follow-up were taken into consideration. Regression analysis was performed to investigate statistical relationships between the occurrence and type of endoleak and preoperative patient and morphologic characteristics, operative details, type of device, and experience of the operating team. In addition, postoperative changes in aneurysmal morphology, the need for secondary interventions, conversions to open repair, aneurysmal rupture, and mortality during follow-up were compared between these study groups., Results: Patients in group A had a higher prevalence of a patent inferior mesenteric artery compared with patients without endoleak. Patients in group B were treated more frequently than patients in group C by an operating team with experience of less than 30 procedures. The mean follow-up period was 15.4 months. Secondary interventions were needed in 13% of the patients. Rupture of the aneurysm during follow-up occurred in 0.52% (1/191) in group A, 3.37% (10/297) in group B, and 0.25% (5/1975) in group C. Life table analysis comparing the three study groups demonstrated a significantly higher rate of rupture in group B than in group C (P =.002). The incidence of conversion to open repair during follow-up was higher in group B than in the other two study groups (P <.01). Death was related to the aneurysm or to endovascular repair of the aneurysm in 7% of patients. Secondary outcome success, defined as absence of rupture and conversion, was significantly higher in group A and C compared with that in group B (P =.006 and P =.0001, respectively)., Conclusions: The presence of device-related endoleaks correlated with a higher risk of aneurysmal rupture and conversion compared with patients without type I or III endoleaks. Type II endoleak was not associated more often with these events. Consequently, intervention in type II endoleak should only be performed in case of increase of aneurysm size.

Objective: Endovascular abdominal aortic aneurysm repair (EAR) can be performed in patients whose conditions were previously considered unfit for conventional treatment of the aneurysm. However, because the life span in this category of patients often is limited because of serious comorbidity, the efficacy of EAR in prolonging life expectancy remains uncertain. This study involves the evaluation of preoperative risk classification and an assessment of the outcome of interventions., Methods: The data of 3075 patients, who underwent operation in 101 European institutions that collaborated in the EUROSTAR Registry, were assessed. Only the patients who had been prospectively enrolled in the registry were used for this analysis. Patient characteristics, operative risk factors, procedural details, and types of devices were correlated with preoperative estimates of operative risk, early and late mortality, complications, and primary and secondary outcome success rates. In addition, the intermediate-term survival rates in patients with unfit conditions with EAR (observed series) and with conservative approaches of the aneurysms (rupture rates as derived from the literature) were compared in a mathematical model., Results: Of the overall study group, 2525 patients were at "normal" risk for a surgical procedure (group A), 399 patients had conditions that were considered unfit for open surgery (group B), and 151 patients had conditions that were unfit for general anesthesia (group C). Both unfit categories had significantly more comorbid factors and larger aneurysms than did the patients in good medical condition. Differences were observed in comorbidities between the two high-risk categories, groups B and C. Factors that influenced the abdominal approach (previous laparotomies, hostile abdomen, and obesity) and local anatomic factors (eg, retroperitoneal fibrosis, inflammatory aneurysm, dissections, and enterostomy) were present in 19% of the patients with conditions that were unfit for open surgery and in only 1% of the category unfit for anesthesia. In contrast, severe pulmonary disease was present in 33% of the patients with conditions that were unfit for anesthesia as opposed to 11% of the patients with conditions that were unfit for open surgery. The early and late mortality rates were significantly higher in the unfit categories (groups B and C). Life table results showed a 3-year survival rate of 83% in patients at normal operative risk and of 68% in patients with unfit conditions (P =.0001). An independent correlation with late death was shown for the clinical classification into high-risk groups B and C, pulmonary disease, team experience of less than 60 procedures, and the diameter of the aneurysm. In groups B and C, aneurysms smaller than 6.0 cm were associated with a 2-year survival rate of 80% and larger aneurysms with a rate of 68% (P =.02). This difference was caused by an increased non-aneurysm-related mortality rate in the group with aneurysms of more than 6 cm. The mathematical model showed an advantage of EAR with regard to the reduction of the death rate in patients with unfit conditions as compared with no intervention after 1 year. The advantage of EAR was observed in patients with AAAs between 5 and 6 cm and with larger aneurysms., Conclusion: Early and late mortality rates were increased in patients with the preoperative clinical diagnosis "unfit for open surgery and general anesthesia" as compared with patients at "normal" operative risk. EAR appeared of potential benefit in patients with unfit conditions, regardless of the aneurysm diameter. The life expectancy of patients at high risk who are considered for EAR should be longer than 1 year before any realistic gain in life span can be anticipated.

Purpose: We used (31)P magnetic resonance spectroscopy (MRS) and near-infrared spectroscopy (NIRS) as a means of quantifying abnormalities in calf muscle oxygenation and adenosine triphosphate (ATP) turnover in peripheral vascular disease (PVD)., Methods: Eleven male patients with PVD (mean age, 65 years; range, 55-76 years) and nine male control subjects of similar age were observed in a case-control study in vascular outpatients. Inclusion criteria were more than 6 months' calf claudication (median, 1.5 years; range, 0.6-18 years); proven femoropopliteal or iliofemoral occlusive or stenotic disease; maximum treadmill walking distance (2 km/h, 10 degrees gradient) of 50 to 230 m (mean, 112 m); ankle-brachial pressure index of 0.8 or less during exercise (mean, 0.47; range, 0.29-0.60). Exclusion criteria included diabetes mellitus, anemia, and magnet contraindications. Simultaneous (31)P MRS and NIRS of lateral gastrocnemius was conducted during 2 to 4 minutes of voluntary 0.5 Hz isometric plantarflexion at 50% and 75% maximum voluntary contraction force (MVC), followed by 5 minutes recovery. Each subject was studied three times, and the results were combined., Results: Compared with control subjects, patients with PVD showed (1) normal muscle cross-sectional area, MVC, ATP turnover, and contractile efficiency (ATP turnover per force/area); (2) larger phosphocreatine (PCr) changes during exercise (ie, increased shortfall of oxidative ATP synthesis) and slower PCr recovery (47% +/- 7% [mean +/- SEM] decrease in functional capacity for oxidative ATP synthesis, P = .001); (3) faster deoxygenation during exercise and slower postexercise reoxygenation (59% +/- 7% decrease in rate constant, P = .0009), despite reduced oxidative ATP synthesis; (4) correlation between PCr and NIRS recovery rate constants (P < .02); and (5) correlations between smaller walking distance, slower PCr recovery, and reduced MVC (P < .001). The precision of the key measurements (rate constants and contractile efficiency) was 12% to 18% interstudy and 30% to 40% intersubject., Conclusion: The primary lesion in oxygen supply dominates muscle metabolism. Reduced force-generation in patients who are affected more may protect muscle from metabolic stress.

Objective: Perianeurysmal fibrosis (PAF) with involvement of neighbouring viscera can render open repair of inflammatory aneurysms technically difficult and therefore hazardous. For this reason, endovascular repair (EVAR) has been advocated as the preferred approach for this condition. EVAR is known to induce a systemic inflammatory response in patients but the nature of the local response remains unknown. If significant, such a response could exacerbate rather than ameliorate PAF. The aim of the study was to examine the incidence, course and consequences of perianeurysmal fibrosis detected by computerised tomography (CT) before and after EVAR., Material and Methods: The clinical records of patients treated by EVAR and followed for at least 6 months were reviewed. Pre and post-operative CT images were independently graded for PAF by three radiologists according to a standard protocol., Results: PAF was documented preoperatively in six out of a total of 61 patients. In two of these PAF worsened after EVAR resulting in ureteric obstruction and hydronephrosis requiring ureteric stents. In the remaining 4 patients PAF did not reduce postoperatively. PAF of low grade developed postoperatively in 10 out of 55 patients (18%) in whom there was no evidence of PAF on preoperative imaging. Median follow-up was 18 months (range 6-36 months). The development of periaortic fibrosis de novopostoperatively was statistically significant (McNemar's test p=0.002)., Conclusion: EVAR does not seem to reverse PAF if this is present preoperatively and it induces this condition in approximately one sixth of patients without evidence of preoperative PAF. The potential for this adverse inflammatory local response should be taken into account when considering EVAR for treatment of aneurysms with perianeurysmal fibrosis and must be weighed against the perceived benefits of this approach., (Copyright 2001 Harcourt Publishers Limited.)

Objectives: Standardisation of cuff geometry by manufacturing prosthetic precuffed grafts (PCG) theoretically optimises haemodynamic forces. This study was designed in order to determine whether these beneficial flow patterns are replicated in vivo in PCG., Patients and Methods: Flow visualisation and Doppler studies performed on anatomically accurate PCG models characterised in vitro anastomotic flow patterns. Thirty-two patients (median age 68 years) in whom autologous vein was unavailable, underwent bypass using PCG. Post-operative analysis included qualitative assessment of flow within the distal anastomosis using Doppler colour flow mapping. Cardiac gating techniques and assessment of velocity distribution were performed to gain additional information. These in vivo results were validated against the bench studies., Results: A cohesive vortex was identified within the distal anastomosis of in vitro models and had an integral relationship with the cardiac cycle. This flow structure was also characterised using Doppler colour flow mapping in both longitudinal and transverse planes, confirming the location of the vortex within the body and proximal part of the anastomosis. Twenty-two patients (69%) undergoing bypass with a PCG underwent successful Doppler assessment one week post-operatively, of whom 17 (77%) had a vortical flow structure identified at the distal anastomosis, similar to that characterised in vitro. Cardiac gating verified the same integral relationship of the vortex with the cardiac cycle as that described in vitro., Conclusion: The geometric configuration of precuffed grafts induced vortices within the distal anastomoses in 17 out of 22 patients undergoing arterial reconstruction, thereby harnessing the haemodynamic forces that may suppress anastomotic hyperplasia and improve patency rates., (Copyright 2001 Harcourt Publishers Limited.)

Objectives: the aim of this study was to assess the relationship between patient factors, the anatomy of the proximal aneurysm neck; the type of endovascular graft; and the consequences of graft/neck size mismatch and the occurrence of proximal endoleak. Design multicentre clinical study., Materials: of a total of 2194 patients, 2146 underwent successful endovascular repair of infra-renal abdominal aortic aneurysms (AAA)., Methods: endoleaks were identified by radiological imaging immediately after completion of the procedure as per study protocols. Clinical and anatomical features of AAA in patients with endoleak were compared to patients without endoleak and data were analysed using the Chi-square test. A multivariate logistic regression model was constructed by selecting variables found to be significantly associated with complications in a univariate analysis., Results: intra-operative endoleak was observed in 16.7% overall, and 3.3% were noted to have proximal endoleak. Aneurysm size larger than 60 mm (p =0.004), ex-smokers ( p =0.005) and age over 75 years ( p =0.01) were independently associated with endoleak of all types. Univariate and multivariate analysis revealed correlation between proximal endoleak and (i) diameter of the aneurysm neck-proximal (D2a), middle (D2b), distal (D2c), at all levels (p <0.005); (ii) proximal aortic neck length ( p =0.0001); (iii) aortic device diameter ( p =0.0024). No correlation was identified for angulation and form of the aortic neck. A model of the frequency of proximal endoleak, in relation to the ratio of the aortic device diameter to the distal aortic neck diameter, revealed that endoleak decreased when the aortic device diameter became oversized by more than 10% and confidence intervals remained tight for up to and over 20% oversize., (Copyright 2001 Harcourt Publishers Limited.)

Objectives: since cuff dimensions are variable, we studied the influence of cuff geometry on flow mechanics, in an attempt to identify the optimum configuration., Materials and Methods: bench studies involved the manufacture of anatomically accurate models of varying cuff dimensions, perfused in a specifically designed flow rig, simulating physiological conditions. Flow visualisation studies incorporating laser illumination of tracer particles enabled accurate analysis of flow patterns., Results: the vortex created within the proximal cuff of each model during the deceleration phase of the cardiac cycle was strongly influenced by the aspect ratio (AR=cuff height:length). The standard and high cuffs (AR=1.63 and 1.18, respectively) demonstrated cohesive vortices and stable flow patterns. Low and long cuffs (AR=2.6 and 2.25, respectively) created more complex vortices with large areas of flow separation and low velocities., Conclusions: aspect ratio has an important influence on flow within the distal anastomosis, with cuff dimensions of 13 mm long and 8-11 mm high (standard and high cuffs) creating beneficial flow patterns anticipated to optimise wall shear stress and inhibit myointimal hyperplasia., (Copyright 2001 Harcourt Publishers Limited.)

Neurons of adults apparently lack the components necessary to complete the cell division process. Therefore, in Alzheimer disease, the increased expression of cell cycle-related proteins in degenerating neurons likely leads to an interrupted mitotic process associated with cytoskeletal abnormalities and, ultimately, neuronal degeneration. In this study, to further delineate the role of mitotic processes in the pathogenesis of Alzheimer disease, we undertook a study of polo-like kinase (Plk), a protein that plays a crucial role in the cell cycle. Our results show disease-related increases in Plk in susceptible hippocampal and cortical neurons in comparison to young or age-matched controls. An increase in neuronal Plk further implicates aberrations in cell cycle control in the pathogenesis of Alzheimer disease and provides a novel mechanistic basis for therapeutic intervention.

Objective: The EUROSTAR (European Collaborators on Stent/graft techniques for aortic aneurysm repair) Registry was established in 1996 to collect data on the outcome of treatment of patients with infrarenal aortic aneurysms with endovascular repair. To date, 88 European centers of vascular surgery have contributed. The purpose of the study was to evaluate the results of this treatment in the medium term (up to 4 years) according to the analysis of "hard" or primary end points of rupture, late conversion, and death., Patients and Methods: Patients with aortic aneurysms suitable for endovascular aneurysm repair were notified to the EUROSTAR Data Registry Centre before treatment to eliminate bias due to selective reporting. The following information was collected on all patients: (1) demographic details and the anatomic characteristics of their aneurysms, (2) details of the endovascular device used, (3) complications encountered during the procedure and the immediate outcome, (4) results of contrast enhanced computed tomographic imaging at 3, 6, 12, and 18 months after operation and at yearly intervals thereafter, and (5) all adverse events. Life table analysis was performed to determine the cumulative rates of (1) death from all causes, (2) rupture, and (3) late conversion to open repair. Risk factors for rupture and late conversion were identified through regression analysis., Results: By March 2000, 2464 patients had been registered, and their mean duration of follow-up was 12.19 months (SD, 12.3 months). There were 14 patients with confirmed rupture of their aneurysms. The cumulative rate (risk) of rupture was approximately 1% per year. Emergency surgery was undertaken in 12 (86%) patients, of whom five (41.6%) survived. Two patients who were not treated surgically also died, which resulted in an overall death rate of 64.5% (9/14) of the patients. Significant risk factors for rupture were proximal type I endoleak (P =.001), midgraft (type III) endoleak (P =.001), graft migration (P =.001), and postoperative kinking of the endograft (P =.001). Forty-one patients underwent late conversion to open repair with a perioperative mortality rate of 24.4% (10/41). The cumulative rate (risk) of late conversion was approximately 2.1% per year. Risk factors (indications) for late conversion were proximal type I endoleak (P =. 001), midgraft (type III) endoleak (P =.001), type II endoleak (P =. 003), graft migration (P =.001), graft kinking (P =.001), and distal type I endoleak (P =.001)., Conclusions: Endovascular repair of infrarenal aortic aneurysms with the first- and second-generation devices that predominated in this study was associated with a risk of late failure, according to an analysis of observed hard end points of 3% per year. Action taken to address the risk factors identified by the study may improve results in the future.

Objective: Interposition of a vein cuff between a prosthetic infrainguinal bypass graft and a recipient infrageniculate artery can improve graft patency. There is evidence that the improved performance may be explained by a redistribution of myointimal hyperplasia (MIH) away from the critical areas at the heel and toe of the cuff-artery anastomosis. It is widely accepted that there is an association between hemodynamic forces, more specifically, low wall shear stress (WSS), and the development of MIH. The aim of this study was to determine whether the reported redistribution of MIH in the interposition vein cuff (IVC) may be explained by differences in magnitude and distribution of WSS. Design of Study and Method: Detailed flow velocity measurements were made in life-size models of conventional end-to-side (ETS) and IVC anastomoses using a two-component laser Doppler anemometer under pulsatile flow conditions. Velocity vectors were determined in the plane of symmetry of the anastomosis, and the variation of WSS was estimated from near-wall velocity measurements on the floor and upper wall of the artery., Results: The main flow features in the ETS anastomosis were flow separation at the graft hood, strong radial velocity at the heel, and a stagnation point on the floor of the artery that moved slightly during the flow cycle. In the IVC anastomosis, a coherent vortex that occupied most of the cuff volume was present from the systolic deceleration phase to end diastole. A stagnation point on the anastomosis floor was found to oscillate by about 4 mm. Critical regions of low mean WSS (ie, below 0.5 N/m(2)) were identified. In the ETS anastomosis, they were found at the heel and along the floor. In the IVC anastomosis, low mean WSS was found only on the floor, and it was generally less extensive than in the ETS anastomosis., Conclusion: The vein cuff anastomosis alters the mean WSS distribution within the recipient artery and removes the area of low WSS at the heel. This may explain the redistribution of MIH away from important sites in the recipient artery.

Objective: To determine whether freedom from endoleak after endovascular repair of abdominal aortic aneurysm (EVAR) is a reliable guide to freedom from persistent or recurrent pressurisation of the aneurysm sac (endotension) and therefore freedom from risk of rupture., Patients and Methods: The records of 55 patients followed for more than 3 months after EVAR were reviewed to correlate the presence or absence of endoleak on contrast-enhanced CT and/or angiography with changes in maximum aneurysm diameter (DMAX)., Results: in 22 (40%) patients there was no significant change in DMAX during follow-up. In 21 of these no endoleak was observed on CT or angiography. One patient developed a secondary side-branch endoleak which remains under observation. In 18 (33%) patients, DMAX decreased during follow-up. Thirteen of these remained free of endoleak. Four patients developed secondary endoleaks which were treated by secondary intervention. One patient with persistent primary endoleak suffered fatal aneurysm rupture three days before planned intervention. DMAX increased in 15 (27%) patients. In only five of these could an endoleak be identified on CT and/or angiography. One primary side-branch endoleak persists following failed embolisation. Four secondary endoleaks have been corrected by secondary intervention. Four of the remaining 10 patients died suddenly from unknown cause. All had DMAX greater than 65 mm at last follow-up. One patient underwent late conversion, which suggested continued pressurisation through thrombus at the site of a "sealed" primary proximal endoleak. Two patients are scheduled to undergo embolisation of patent side-branches revealed only by Levovist enhanced Duplex scanning and three patients remain under observation., Conclusion: Freedom from endoleak on conventional imaging incorrectly suggested freedom from endotension in 10 (18%) of our patients. Follow-up after endovascular repair must include regular measurement of DMAX and/or aneurysm sac volume to identify those patients who remain at risk of rupture., (Copyright 1999 Harcourt Publishers Ltd.)

Objective: the outcomes for patients after endovascular treatment of abdominal aortic aneurysm (AAA) are determined primarily by the endpoints of death and endoleaks, the latter representing continued risk of rupture. The data of a multicentre registry were analysed with regard to the early outcome of stent-graft procedures for AAA and the complications associated with this treatment. In addition, the results during follow-up were analysed by determining mortality and endoleak development as separate endpoints and as a combined endpoint defined as endoleak-free survival., Setting: 38 European institutions of Vascular Surgery collaborating in a multicentre registry project., Patients and Methods: 899 patients with AAA underwent between May 1994 and March 1998 elective endovascular repair (818 men and 81 women; mean age 69 years). 80 (8.9%) of the patients had medical conditions that excluded them from open repair. 818 (91%) of patients had a bifurcated device, 63 (7%) had a straight tube graft, and only 18 (2%) had an aorto-uni-iliac device. Clinical examination and contrast-enhanced computed tomography was performed at fixed follow-up intervals to assess increase or decrease of the maximum transverse diameter (MTD). Endoleaks observed at follow-up were discriminated into persistent endoleak and temporary endoleak. The latter is defined as single time observed endoleaks or with two or more negative imaging studies between observed endoleaks. Life-table analyses were used to calculate the rates of freedom-from-endoleak (no endoleak at any time), freedom-from-persistent endoleak (no persistent endoleak), patient survival, and persistent-endoleak-free-survival., Results: the median follow-up of this patient series was 6.2 months. The ratio between observed and expected follow-up data was 82% for the overall follow-up period. However, at 18 months of follow-up this rate was only 45%. The number of patients followed during this period was sufficient to allow statistically meaningful assessment. The MTD in patients with temporary endoleaks demonstrated a significant decrease at 6 to 12 months compared to preoperative values (mean 57 and 53 respectively, p =0.004). In patients with persistent endoleaks there was no change between the preoperative and 6-month MTD (mean 57 and 60 mm respectively). At 6 and 18 months freedom-from-endoleak was 83% and 74% and freedom-from-persistent endoleak was 93% and 90%, respectively. The 18-month cumulative patient survival was 88% and the main outcome measure, the persistent endoleak-free-survival was 79%., Conclusions: the MTD decreases in patients with temporary endoleak, but not in patients with persistent endoleak. Therefore, the use of the rate of freedom-from-persistent endoleak, reflecting absence of persisting endoleaks to estimate the prognosis with regard to the AAA, is justified. Determining persistent endoleak-free survival appears a rational approach to provide a realistic outlook for patients with stent-grafted AAA. The observed 18-month endoleak-free survival reflects a satisfactory mid-term result., (Copyright 1999 W.B. Saunders Company Ltd.)

Objectives: To compare graft patency and limb salvage rate following femoro-infrapopliteal bypass using ePTFE grafts with and without the addition of adjuvant arterio-venous fistula., Design: A prospectively randomised controlled trial., Materials: Patients referred to two teaching hospital vascular surgery units in the U.K. for the treatment of critical limb ischaemia., Methods: Eighty-seven patients (M:F; 2.3:1) undergoing 89 femoro-intrapopliteal bypass operations with ePTFE grafts for critical limb ischaemia were randomly allocated to have AVF included in the operative procedure (n = 48) or to a control group without AVF (n = 41). An interposition vein-cuff was incorporated at the distal anastomosis in all patients., Results: The cumulative rates of primary patency and limb salvage at 1-year after operation for patients with AVF were 55.2% and 54.1% compared to 53.4% and 43.2%, respectively, for the control group. The differences between the AVF and control groups did not reach statistical significance, in terms of either graft patency or limb salvage, at any stage after operation (Log-Rank test)., Conclusions: AVF confers no additional significant clinical advantage over interposition vein cuff in patients having femoro-infrapopliteal bypass with ePTFE grants for critical limb ischaemia.

Objectives: Interposition vein cuffs improve the patency of below-knee ePTFE arterial grafts, and there is evidence that they do so, at least in part, by modifying the distribution of myointimal hyperplasia (MIH) at the distal anastomosis. Alteration of local haemodynamics is one of the mechanisms which might be involved. The purpose of this study was to characterise the local haemodynamics within an interposition vein cuff., Material and Methods: Flow patterns have been analysed in a laboratory model of cuffed anastomosis and compared with observations made in patients by cine intra-arterial digital subtraction angiography (IA DSA) and dynamic colour duplex scanning., Results: In contrast to non-cuffed anastomoses in which the flow is predominantly laminar, cuffed anastomoses are associated with the formation of a coherent vortex., Conclusion: High frictional forces or shear stress exerted upon the arterial wall by the vortex could explain the beneficial effect of a cuff upon anastomotic MIH, in which case the optimal configuration of small vessel anastomoses would be that which most effectively promotes the formation of this type of vortex.

In this study, we demonstrate that two important regulators of the cell cycle, cyclin-dependent kinase-4 and its inhibitor p16, are increased in the brains of cases of Alzheimer's disease patients compared with age-matched controls. Both proteins are increased in the pyramidal neurons of the hippocampus, including those neurons containing neurofibrillary tangles and granulovacuolar degeneration. As p16 is not normally found in terminally differentiated neurons, it seems paradoxical that it is increased in Alzheimer's disease unless it is responding to increases in cyclin-dependent kinase-4 or other cell cycle regulators. Induction of the latter, a protein that signals re-entry and progression through the cell cycle, may itself be the consequence of alpha response to a growth stimulus. Re-entry into the cell cycle is likely deleterious in terminally differentiated neurons and may contribute to the biochemical abnormalities, such as oxidative stress and hyperphosphorylated tau protein, as well as the neuronal degeneration characteristic of the pathology of Alzheimer's disease.

A prototype simulator for training in endovascular repair of abdominal aortic aneurysms (AAA) has been developed. Employing transparent models of human AAA complete with renal, iliac and femoral arteries, this system allows accurate simulation of aortography, road-mapping, catheter guidewire manipulation and stent-graft deployment while obviating the need for ionising radiation.

Research on children's causal thinking has emphasized the perception of temporal and spatial contiguity between cause and effect. However, our causal judgements often involve a contrast between a perceived sequence (A, then B) and a counterfactual case (in the absence of A, then not B). In three experiments, children's capacity for such counterfactual thinking was assessed. In Experiment I, children aged 3-5 years observed a sequence such as A causing B. Subsequently, they replied quite accurately to a question about a counterfactual sequence, for example: "What if A had not occurred, then B or not B?". In Experiment 2, children were asked about two counterfactual antecedents, one that would not have caused B, and one that (like the actual antecedent) would also have caused B. Children differentiated between the two types of antecedent. Finally, in Experiment 3, children heard stories in which the protagonist chose a course of action that led to a minor mishap (e.g., drawing with a black pen and getting inky fingers), having rejected an option that would have prevented it in experimental stories (e.g., using a pencil) or an option that would have led to an equivalent outcome in control stories (e.g., using a blue pen). Children aged 3 and 4 years often cited the failure to adopt another course of action as the cause of the mishap and, particularly in experimental stories, they focused on the rejection of the alternative option. Children's use of counterfactual thinking is discussed in relation to contemporary accounts of causal reasoning.