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Explores the clinical variables associated with foot pain in diabetic patients. Relationship between foot pain and functional impairments and disabilities; Occurrence of foot pain in diabetic patients with sensory neuropathy; Level of affective well-being.

Abstract Background The additional benefit of lifestyle interventions in patients receiving cardioprotective drug treatment to improve cardiovascular risk profile is not fully established. The objective was to evaluate the effectiveness of a target-driven multidisciplinary structured lifestyle intervention programme of 6 months duration aimed at maximum reduction of cardiovascular risk factors in patients with cardiovascular disease (CVD) compared with usual care. Methods A single centre, two arm, parallel group randomised controlled trial was performed. Patients with stable established CVD and at least one lifestyle-related risk factor were recruited from the vascular and cardiology outpatient departments of the university hospital. Blocked randomisation was used to allocate patients to the intervention (n = 71) or control group (n = 75) using an on-site computer system combined with allocations in computer-generated tables of random numbers kept in a locked computer file. The intervention group received the comprehensive lifestyle intervention offered in a specialised outpatient clinic in addition to usual care. The control group continued to receive usual care. Outcome measures were the lifestyle-related cardiovascular risk factors: smoking, physical activity, physical fitness, diet, blood pressure, plasma total/HDL/LDL cholesterol concentrations, BMI, waist circumference, and changes in medication. Results The intervention led to increased physical activity/fitness levels and an improved cardiovascular risk factor profile (reduced BMI and waist circumference). In this setting, cardiovascular risk management for blood pressure and lipid levels by prophylactic treatment for CVD in usual care was already close to optimal as reflected in baseline levels. There was no significant improvement in any other risk factor. Conclusions Even in CVD patients receiving good clinical care and using cardioprotective drug treatment, a comprehensive lifestyle intervention had a beneficial effect on some cardiovascular risk factors. In the present era of cardiovascular therapy and with the increasing numbers of overweight and physically inactive patients, this study confirms the importance of risk factor control through lifestyle modification as a supplement to more intensified drug treatment in patients with CVD. Trial registration ISRCTN69776211 at http://www.controlled-trials.com

Abstract Background Non-participants can have a considerable influence on the external validity of a study. Therefore, we assessed the socio-demographic, health-related, and lifestyle behavioral differences between participants and non-participants in a comprehensive CVD lifestyle intervention trial, and explored the motives and barriers underlying the decision to participate or not. Methods We collected data on participants (n = 50) and non-participants (n = 50) who were eligible for inclusion in a comprehensive CVD lifestyle interventional trial. Questionnaires and a hospital patient records database were used to assess socio-demographic, health-related and lifestyle behavioral variables. Univariate and multivariate logistic regression was used to describe the relationship between explanatory variables and study participation. Furthermore, motives and barriers that underlie study participation were investigated by means of questionnaires. Results Participants were younger, single, had a higher level of education and were employed. No statistically significant differences were found in health measures and behavioral variables. The motives for participation that were most frequently reported were: the perception of being unhealthy and willingness to change their lifestyle. The main barriers reported by non-participants were financial arguments and time investment. Conclusion The differences between participants and non-participants in a lifestyle intervention trial are in mainly demographic factors. The participants consent in order to alter their lifestyle, and/or because they want to improve their health. To minimize non-participation, it is recommended that access to a lifestyle intervention program should be easy and cause no financial restraints. Trial registration ISRCTN69776211.

Introduction: The aim of our study was to evaluate the long term results of Endoscopic Thoracic Sympathectomy (ETS) in the management of upper limb ischemia (ULI)., Methods: We retrospectively reviewed the records of all consecutive patients who underwent ETS for ULI between January 1994 and May 2009. A standardized questionnaire was used to evaluate the long term success, morbidity and overall patient satisfaction., Results: Thirty-five patients (20 female, mean age 49 years (range 23-79)) underwent bilateral (n = 9) and unilateral (n = 27) ETS procedures, respectively. Six patients had Primary (idiopathic) Raynaud Disease. Twenty-nine patients had upper limb ischemia secondary to systemic disorders (n = 12), embolic disease (n = 10), occlusion of the arteries of the arm (n = 5) or hypothenar hammer syndrome (n = 2). Tissue loss at time of surgery was present in nineteen patients. Short term beneficial effects were reported by 12 patients (63%). Eleven of the 35 patients experienced a total of 13 complications or adverse events, whereof 11 were minor or transient. Limb salvage was unsuccessful in three patients because of major amputations (n = 2) or severe functional impairment (n = 1). Necrotectomies or minor amputations without functional impairment were performed in 9 patients. Medium or long term follow up (mean 98 months (range 18-198) was available in 19 out of 22 living patients(86%). Long term beneficial effects were reported by 10 (53%). Overall patient satisfaction was 56%. Compensatory sweating was experienced by 11 patients (58%)., Conclusion: Although the long term efficacy of ETS in our study was moderate (53%), due to its low invasiveness ETS is a valuable option in the management of ULI., (Copyright © 2016. Published by Elsevier Ltd.)

Background: Massive bleeding in patients with aortoenteric fistula (AEF) may be preceded by minor, intermittent gastrointestinal (GI) blood loss, termed the "herald bleed." The aims of this retrospective study were to: (i) analyze the interval between the herald bleed and onset of major GI hemorrhage and/or diagnosis of AEF and (ii) to evaluate the diagnostic roles of endoscopy and computed tomography imaging., Methods: Analysis of all patients diagnosed with AEF or iliac-enteric fistulas between 1994 and 2013 in a single institution., Results: In 31 of a total of 34 fistula cases, GI bleeding was the presenting symptom. Of these, 17 of 31 presented with herald bleed while 14 of 31 presented with massive GI bleeding. In patients with a herald bleed, median time from first bleeding to diagnosis was 14 (2-137) days. In 5/17 patients, herald bleeding preceded major hemorrhage with a median of 6 (4-92) days before a diagnosis of AEF was made or intervention could be initiated. CT angiography (CTA) showed abnormalities associated with a fistula in 27 (79%) cases, of which in 12 (35%) cases a fistula was actually identified. Esophagogastroduodenoscopy (EGD) demonstrated a fistula in 8 (25%) patients, while 50% of EGDs were completely normal., Conclusions: Any patient with history of aortic surgery and GI bleeding should be considered to have an AEF until proven otherwise. The sensitivity of CTA for detecting AEF is substantially greater than that of EGD. The time interval between herald bleed and subsequent massive hemorrhage associated with AEF is unpredictable but may be as short as 4 days., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aims: To investigate the feasibility, safety and efficacy of the Nurse-Driven Diabetes In-Hospital Treatment protocol (N-DIABIT), which consists of nurse-driven correctional therapy, in addition to physician-guided basal therapy, and is carried out by trained ward nurses., Methods: Data on 210 patients with diabetes consecutively admitted in the 5-month period after the introduction of N-DIABIT (intervention group) were compared with the retrospectively collected data on 200 consecutive patients with diabetes admitted in the 5-month period before N-DIABIT was introduced (control group). Additional per-protocol analyses were performed in patients in whom mean patient-based protocol adherence was ≥ 70% (intervention subgroup, n = 173 vs. control subgroup, n = 196)., Results: There was no difference between the intervention and the control group in mean blood glucose levels (8.9 ± 0.1 and 9.1 ± 0.2 mmol/l, respectively; P = 0.38), consecutive hyperglycaemic (blood glucose ≥ 10.0 mmol/l) episodes; P = 0.15), admission duration (P = 0.79), mean number of blood glucose measurements (P = 0.21) and incidence of severe hypoglycaemia (P = 0.29). Per-protocol analyses showed significant reductions in mean blood glucose levels and consecutive hypoglycaemia and hyperglycaemia in the intervention compared with the control group., Conclusions: Implementation of N-DIABIT by trained ward nurses in non-intensive care unit diabetes care is feasible, safe and non-inferior to physician-driven care alone. High protocol adherence was associated with improved glycaemic control., (© 2015 Diabetes UK.)

Apoptosis of endothelial cells related to homocysteine (Hcy) has been reported in several studies. In this study, we evaluated whether reactive oxygen species (ROS)-producing signaling pathways contribute to Hcy-induced apoptosis induction, with specific emphasis on NADPH oxidases. Human umbilical vein endothelial cells were incubated with 0.01-2.5 mM Hcy. We determined the effect of Hcy on caspase-3 activity, annexin V positivity, intracellular NOX1, NOX2, NOX4, and p47(phox) expression and localization, nuclear nitrotyrosine accumulation, and mitochondrial membrane potential (ΔΨ m). Hcy induced caspase-3 activity and apoptosis; this effect was concentration dependent and maximal after 6-h exposure to 2.5 mM Hcy. It was accompanied by a significant increase in ΔΨ m. Cysteine was inactive on these parameters excluding a reactive thiol group effect. Hcy induced an increase in cellular NOX2, p47(phox), and NOX4, but not that of NOX1. 3D digital imaging microscopy followed by image deconvolution analysis showed nuclear accumulation of NOX2 and p47(phox) in endothelial cells exposed to Hcy, but not in control cells, which coincided with accumulation of nuclear nitrotyrosine residues. Furthermore, Hcy enhanced peri-nuclear localization of NOX4 coinciding with accumulation of peri-nuclear nitrotyrosine residues, a reflection of local ROS production. p47(phox) was also increased in the peri-nuclear region. The Hcy-induced increase in caspase-3 activity was prevented by DPI and apocynin, suggesting involvement of NOX activity. The data presented in this article reveal accumulation of nuclear NOX2 and peri-nuclear NOX4 accumulation as potential source of ROS production in Hcy-induced apoptosis in endothelial cells.

Objective: We have previously shown that homocysteine (Hcy) induces phosphatidylserine (PS) exposure, apoptosis and necrosis in human endothelial cells. Since it has been suggested that S-adenosylhomocysteine (SAH) is the main causative factor in Hcy-induced pathogenesis of cardiovascular disease, we evaluate here whether the cytotoxic Hcy effect in endothelial cells is also SAH dependent., Methods and Results: Human umbilical vein endothelial cells (HUVECs) were exposed to the following conditions: (1) non-treated control (resulting in 2.8 nM intracellular SAH and 3.1 μM extracellular l-Hcy); and incubation with (2) 50 μM adenosine-2,3-dialdehyde (ADA; resulting in 17.7 nM intracellular SAH and 3.1 μM extracellular l-Hcy), (3) 2.5 mM Hcy (resulting in 20.9 nM intracellular SAH and 1.8 mM extracellular l-Hcy), and (4) 1, 10 and 100 μM SAH. We then determined the effect of treatment on annexin V-positivity, caspase-3 activity, cytochrome c release (sub)cellular expression of NOX2, NOX4, p47(phox) and nitrotyrosine, and H(2)O(2). Both Hcy and ADA significantly increased PS exposure (n=5), caspase-3 activity (n=6) and cytochrome c release (n=3). Incubation with extracellular SAH alone did not affect cell viability. Both Hcy and ADA also induced similar increases in nuclear NOX2 and (peri)nuclear NOX4, coinciding with (peri)nuclear p47(phox) expression and local reactive oxygen species (ROS) (n=3). Inhibition of NOX-mediated ROS by the flavoenzyme inhibitor diphenylene iodonium (DPI) significantly decreased apoptosis induction (n=3) and ROS production (n=3)., Conclusion: SAH induces PS exposure and apoptosis in endothelial cells independently of Hcy. Our study therefore shows that Hcy-mediated endothelial dysfunction, as determined in the cell model used, is mainly due to SAH accumulation., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

We aimed to compare the long-term results of three different strategies for treatment of patients with primary (spontaneous or effort related) subclavian vein thrombosis (PSVT). We followed 45 consecutive patients who had been treated for PSVT receiving either oral anticoagulant therapy only (n = 14, group 1); thrombolysis followed by anticoagulant therapy (n = 14, group 2); or thrombolysis, transaxillary first rib resection and anticoagulant therapy (n = 17, group 3). Endpoints were persisting symptoms and quality of life (QoL). The latter was assessed with the EuroQol (EQ-5D) questionnaire at the end of follow-up. The design is a case-control study with three different groups. Predictors for residual symptoms and QoL were analyzed with logistic and linear regression analysis. Patients in groups 2 and 3 had significantly less pain, swelling and fatigue in the afflicted limb at six weeks. There was no difference in pain (P = 0.90), swelling (P = 0.58), fatigue (P = 0.61), functional impairment (P = 0.61), recurrence (P = 0.10) or QoL (P = 0.25) between groups at the end of follow-up (mean follow-up 57 months [range 2-176, SD ± 46]). Treatment strategy was not predictive of QoL (P = 0.91, analysis of variance). No differences in long-term symptoms or QoL between patients with successful and unsuccessful thrombolysis were present. In conclusion, thrombolysis with or without first rib resection does not appear to contribute to lasting symptom reduction and improvement of QoL in this study. The effect of thrombolysis may be limited to short-term symptom relief. Transaxillary first rib resection was not associated with improved late outcome (symptoms, QoL) and did not reduce recurrence rate.

We previously found that homocysteine (Hcy) induced plasma membrane flip-flop, apoptosis, and necrosis in cardiomyocytes. Inactivation of flippase by Hcy induced membrane flip-flop, while apoptosis was induced via a NOX2-dependent mechanism. It has been suggested that S-adenosylhomocysteine (SAH) is the main causative factor in hyperhomocysteinemia (HHC)-induced pathogenesis of cardiovascular disease. Therefore, we evaluated whether the observed cytotoxic effect of Hcy in cardiomyocytes is SAH dependent. Rat cardiomyoblasts (H9c2 cells) were treated under different conditions: (1) non-treated control (1.5 nM intracellular SAH with 2.8 μM extracellular L -Hcy), (2) incubation with 50 μM adenosine-2,3-dialdehyde (ADA resulting in 83.5 nM intracellular SAH, and 1.6 μM extracellular L -Hcy), (3) incubation with 2.5 mM D, L -Hcy (resulting in 68 nM intracellular SAH and 1513 μM extracellular L -Hcy) with or without 10 μM reactive oxygen species (ROS)-inhibitor apocynin, and (4) incubation with 100 nM, 10 μM, and 100 μM SAH. We then determined the effect on annexin V/propodium iodide positivity, flippase activity, caspase-3 activity, intracellular NOX2 and p47(phox) expression and localization, and nuclear ROS production. In contrast to Hcy, ADA did not induce apoptosis, necrosis, or membrane flip-flop. Remarkably, both ADA and Hcy induced a significant increase in nuclear NOX2 expression. However, in contrast to ADA, Hcy additionally induced nuclear p47(phox) expression, increased nuclear ROS production, and inactivated flippase. Incubation with SAH did not have an effect on cell viability, nor on flippase activity, nor on nuclear NOX2-, p47phox expression or nuclear ROS production. HHC-induced membrane flip-flop and apoptosis in cardiomyocytes is due to increased Hcy levels and not primarily related to increased intracellular SAH, which plays a crucial role in nuclear p47(phox) translocation and subsequent ROS production.

Background: Thoracic sympathectomy is used in the management of a variety of upper limb disorders. We have analyzed the evidence for thoracic sympathectomy in the management of digital ischemia., Methods: We reviewed the English literature between 1980 and 2010. Our analysis included reports with the clinical end points of relief, recurrence of symptoms or healing of ulcers, or both. Primary Raynaud disease (PRD) and secondary Raynaud phenomenon (SRP) were analyzed separately., Results: An initial postoperative positive effect was reported in 92% of PRD patients and in 89% of SRP patients. Long-term beneficial effect was 58% for PRD and 89% for SRP. Ulcer healing or improvement was achieved in 95%., Conclusions: The available evidence suggests that thoracic sympathectomy has a role in the treatment of severe PRD and SRP, albeit with better results in SRP patients than in PRD patients. In case of digital ulceration, thoracic sympathectomy may maximize tissue preservation or prevent amputation., (Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Aims: Increased levels of homocysteine (Hcy) form an independent risk factor for cardiovascular disease. In a previous study we have shown that Hcy induced phosphatidylserine (PS) exposure to the outer leaflet of the plasma membrane in cardiomyocytes, inducing a pro-inflammatory phenotype. In the present study the mechanism(s) involved in Hcy-induced PS exposure were analyzed., Methods: H9c2 rat cardiomyoblasts were subjected to 2.5 mM D,L-Hcy and analyzed for RhoA translocation and activity, Rho Kinase (ROCK) activity and expression and flippase activity. In addition, the effect of ROCK inhibition with Y27632 on Hcy-induced PS exposure and flippase activity was analyzed. Furthermore, GTP and ATP levels were determined., Results: Incubation of H9c2 cells with 2.5 mM D,L-Hcy did not inhibit RhoA translocation to the plasma membrane. Neither did it inhibit activation of RhoA, even though GTP levels were significantly decreased. Hcy did significantly inhibit ROCK activation, but not its expression, and did inhibit flippase activity, in advance of a significant decrease in ATP levels. ROCK inhibition via Y27632 did not have significant added effects on this., Conclusion: Hcy induced PS exposure in the outer leaflet of the plasma membrane in cardiomyocytes via inhibition of ROCK and flippase activity. As such Hcy may induce cardiomyocytes vulnerable to inflammation in vivo in hyperhomocysteinaemia patients., (Copyright © 2011 S. Karger AG, Basel.)

Subsequent to myocardial infarction, cardiomyocytes within the infarcted areas and border zones expose phosphatidylserine (PS) in the outer plasma membrane leaflet (flip-flop). We showed earlier that in addition to apoptosis, this flip-flop can be reversible in cardiomyocytes. We now investigated a possible role for Rho and downstream effector Rho-associated kinase (ROCK) in the process of (reversible) PS exposure and apoptosis in cardiomyocytes. In rat cardiomyoblasts (H9c2 cells) and isolated adult ventricular rat cardiomyocytes Clostridium difficile Toxin B (TcdB), a Rho GTPase family inhibitor, C3 transferase (C3), a Rho(A,B,C) inhibitor and the ROCK inhibitors Y27632 and H1152 were used to inhibit Rho-ROCK signaling. PS exposure was assessed via flow cytometry and fluorescent digital imaging microscopy using annexin V. Akt expression and phosphorylation were analyzed via Western blot, and Akt activity was inhibited by wortmannin. The cellular concentration activated caspase 3 was determined as a measure of apoptosis, and flippase activity was assessed via flow cytometry using NBD-labeled PS. TcdB, C3, Y27632 and H1152 all significantly increased PS exposure. TcdB, Y27632 and H1152 all significantly inhibited phosphorylation of the anti-apoptotic protein Akt and Akt inhibition by wortmannin lead to increased PS exposure. However, only TcdB and C3, but not ROCK- or Akt inhibition led to caspase 3 activation and thus apoptosis. Notably, pancaspase inhibitor zVAD only partially inhibited TcdB-induced PS exposure indicating the existence of apoptotic and non-apoptotic PS exposure. The induced PS exposure coincided with decreased flippase activity as measured with NBD-labeled PS flip-flop. In this study, we show a regulatory role for a novel signaling route, Rho-ROCK-flippase signaling, in maintaining asymmetrical membrane phospholipid distribution in cardiomyocytes., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Purpose: In 2003, a dedicated Dutch committee developed evidence-based guidelines for the treatment of inguinal hernia (IH) in children and adults. The aim of this study was to describe trends in hernia care before and after the publication of the guidelines on IH surgery in The Netherlands., Methods: Originally, a retrospective baseline analysis of IH surgery in 90 Dutch hospitals was performed among patients treated for IH in 2001. The results of this baseline analysis were compared with a recently performed second analysis of patients treated for IH in 2005., Results: In children <4 years of age, the study showed a significant decrease of contralateral explorations. In adults, the study showed that significantly more patients were treated with a mesh-based repair in 2005 (95.9 vs. 78.8%, P < 0.01). Moreover, there was an increase of patients with bilateral hernia treated with an endoscopic technique (41.5 vs. 22.3%, P < 0.01) and more patients were treated in day surgery (53.5 vs. 38.6%, P < 0.01). Lastly, a decline in operations performed for recurrent IH in adults was observed (10.9 vs. 13.3%, P < 0.01)., Conclusion: This study showed that most patients with IH in The Netherlands were treated according to the main recommendations of the Dutch evidence-based guidelines.

Background: The purpose of this study was to characterize ipsi- and contralateral cerebral hemodynamics before and after CEA., Methods: Cerebral blood flow, CBV, and MVTT were measured in 10 patients before and after CEA using PET. Absolute and relative values of these parameters were calculated bilaterally for the entire arterial territories and hemispheres., Results: For all territories in both hemispheres, the mean absolute postoperative CBF was significantly increased compared with preoperative CBF (P < .05). Only in MCA was this increase higher in the ipsilateral than in the contralateral hemisphere (P = .02). Cerebral blood volume was unaffected, whereas MVTT decreased in ipsilateral MCA (P = .05)., Conclusions: The present findings suggest that, on the first day after CEA, absolute CBF is increased in all arterial territories on both ipsi- and contralateral sides, but that there are only minor changes in the relative distribution, whereas the CBV was unaffected.

Objective: Transcranial Doppler (TCD) measures blood flow velocities (BFV) and is an indirect method of assessing cerebral blood flow (CBF). Positron emission tomography (PET) is a direct method to measure CBF. This study evaluates the correlations between TCD and PET findings Methods: Nine patients with a symptomatic carotid artery stenosis, who underwent CEA, were studied pre- and post-operatively on the ipsi- and contralateral sides. Measurements of the BFV, CO(2) reactivity, CBF, cerebral blood volume (CBV) and mean vascular transit time (MVTT) were performed using a three-dimensional volume of interest (VOI) for the middle cerebral artery (MCA)., Results: CBF in the MCA region, as measured with PET, shows a good correlation with BFV, as measured with TCD, with similar pattern for total, gray and white matter MCA territory (Pearson's correlation coefficients: 0.751, 0.748 and 0.748, respectively). This correlation was found in the pre-operative as well as the post-operative state. No association could be demonstrated between CO(2) reactivity and CBV or (Pearson's correlation coefficients: 0.051 and 0.166, respectively)., Conclusion: With PET, it is possible to create three-dimensional VOI of arterial territories. CBF measured in these VOI seems to correlate with BFV before and after CEA on ipsi- and contralateral sides, while CBV shows no association with pre-operative CO(2) reactivity.

Aim: To analyze the change of dimethylarginine plasma levels in cirrhotic patients receiving transjugular intrahepatic portosystemic shunt (TIPS)., Methods: To determine arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and nitric oxide (NO) plasma levels, blood samples were collected from the superior cava, hepatic, and portal vein just before, directly after, and 3 mo after TIPS-placement., Results: A significant increase in the arginine/ADMA ratio after TIPS placement was shown. Moreover, TIPS placement enhanced renal function and thereby decreased systemic SDMA levels. In patients with renal dysfunction before TIPS placement, both the arginine/ADMA ratio and creatinine clearance rate increased significantly, while this was not the case in patients with normal renal function before TIPS placement. Hepatic function did not change significantly after TIPS placement and no significant decline in ADMA plasma levels was measured., Conclusion: The increase of the arginine/ADMA ratio after TIPS placement suggests an increase in intracellular NO bioavailability. In addition, this study suggests that TIPS placement does not alter dimethylarginine dimethylaminohydrolase (DDAH) activity and confirms the major role of the liver as an ADMA clearing organ.

Rationale: Nitric oxide (NO) produced in the lung is an important mediator of normal lung development, vascular smooth muscle relaxation, and ventilation perfusion matching. NO is synthesized from arginine by the action of NO-synthase (NOS). Asymmetric dimethylarginine (ADMA), an endogenous derivate of arginine, inhibits NOS and is thereby a determinant of NO synthesis. We compared ADMA and arginine levels in preterm infants requiring mechanical ventilation with preterm infants who did not require mechanical ventilation and determined the relation between ADMA and the length of mechanical ventilation in these infants., Methods: Thirty preterm infants, mean (SD) gestational age 29.3 (1.7) weeks and birth weight 1,340 (350) gram, of the Neonatal Intensive Care Unit of the VU University Medical Center were included. ADMA and arginine were measured in umbilical cord blood and the length of mechanical ventilation (days) was registered., Results: Gestational age and birth weight were significantly smaller in infants requiring mechanical ventilation, but were not significantly correlated with plasma ADMA concentration after birth. Plasma ADMA concentrations were significantly higher in infants who required mechanical ventilation than in infants who did not require mechanical ventilation (1.53 +/- 0.23 and 1.37 +/- 0.14 micromol/L, respectively; P = 0.036). ADMA concentration was significantly related to length of mechanical ventilation (B = 3.4; 95% CI: 1.1-5.6; P = 0.006), also after adjustment for gestational age (B = 2.3; 95% CI: 0.4-4.2; P = 0.024)., Conclusions: Preterm infants who require mechanical ventilation have increased ADMA levels compared to non-ventilated preterm infants. ADMA levels at birth are related to the length of mechanical ventilation. An increased ADMA concentration could reduce NO synthesis, which could lead to insufficient gas exchange and, consequently, a longer period of mechanical ventilation., ((c) 2008 Wiley-Liss, Inc.)

Carotid artery stenosis is an important cause of transient ischaemic attacks (TIAs) and ischaemic strokes, and is associated with a particularly high risk of recurrent stroke both in the acute phase and the long-term. Early secondary preventive measures would therefore seem warranted. Carotid endarterectomy (CEA) is an effectively therapy in patients with a severe symptomatic stenosis. Hypertension is an important risk factor for recurrent stroke both in the acute phase and the long-term. Moreover, hypertension is an important risk factor for complications of CEA. In patients on the waiting list for CEA, following a TIA or a non-disabling ischaemic stroke, it would seem worthwhile to attempt to start antihypertensive treatment after approximately 24 h, and to at least strive after a preoperative systolic blood pressure of < 180 mmHg and a diastolic blood pressure of < 90 mmHg. In patients who cannot undergo surgery in the desirable short run, hypotensive treatment must be considered in the context of secondary prevention. The blood pressure target level depends on the presence or absence of a severe unilateral or bilateral stenosis (> 70% lumen diameter). In postoperative hypertension one must strive after a blood pressure < 140/90 mmHg, thereby avoiding an excessively rapid hypotensive response (> 25% daily). Patients with a TIA or an ischaemic stroke and a carotid artery stenosis must also be treated with antiplatelet agents and a statin, while other vascular risk factors must be controlled.

Two male patients, aged 37 and 56, suffered from neuralgic pain after a Lichtenstein procedure for inguinal hernia repair using prosthetic reinforcement. Since mesh-based repair techniques have decreased the recurrence rate, postoperative inguinal pain has become a major complication of these operations. Three months after surgery, 20% of the patients experience some pain. In 12% of the patients this pain limits daily activities and 1-3% of the patients are invalidated by neuralgic pain. Preventing damage to sensory nerves during the operation is one way of preventing neuralgic pain. Damaged sensory nerves should be excised. Neuralgic pain after the operation may be alleviated by tricyclic antidepressants, opioids or antiepileptic drugs. In selected patients with neuralgic pain neurectomy is indicated. In one of the patients presented the neuralgic pain disappeared after neurectomy of the ilioinguinal nerve. Triple neurectomy in the other patient, however, was unsuccessful.

Objectives: To compare stump pressure (SP), transcranial Doppler (TCD), electroencephalography (EEG) and selective shunting during carotid endarterectomy (CEA) with preoperative positron emission tomography (PET) parameters., Materials and Methods: Preoperative PET measurements and peroperative neuromonitoring were performed in ten patients undergoing CEA for symptomatic carotid artery disease. PET parameters measured were cerebral blood flow (CBF), oxygen extraction fraction (OEF), cerebral oxygen metabolism (CMRO(2)), cerebral blood volume (CBV), mean vascular transit time (MVTT) and cerebral perfusion pressure (CPP). Results of these measurements in ipsilateral medial cerebral artery (MCA), ipsilateral hemisphere and total cerebrum were compared with absolute mean SP, mean SP<40mmHg, TCD, EEG changes and selective shunting., Results: None of the PET parameters showed any significant correlations with peroperative neuromonitoring findings. There were only trends for correlations of CBF and MVTT with TCD changes and of CPP and CMRO(2) with selective shunting., Conclusions: Preoperative PET examinations are not useful for predicting the need for shunting during CEA.

Background: Asymptomatic peripheral arterial disease (PAD) is common amongst the elderly and is a risk factor for cardiovascular morbidity and mortality. PAD can be assessed by non-invasive tests such as the ankle/brachial pressure index (ABPI) at rest and Doppler flow velocity (DFV) scanning, but these tests may underestimate the prevalence of PAD. The aim of this study was to estimate the added value, for the detection of PAD, of the one-minute exercise test, defined as positive if the drop of the ankle systolic pressure was more than 30 mmHg. We also investigated whether the combination of the ABPI at rest and the one-minute exercise test could replace DFV scanning., Materials and Methods: We studied this in a random sample (n = 631) of a 50- to 75-year-old population., Results: Of these subjects 11% (66/631) had an abnormal ABPI (< 0.9) and 16% (102/631) had an abnormal DFV curve. Of this sample 72% of the subjects performed a one-minute exercise test. Of all subjects 6% (27/451) had an abnormal ABPI (< 0.9) and 12% (54/451) had an abnormal DFV curve. The one-minute exercise test revealed seven cases of PAD (beyond the 67 already identified) which were not detected by an abnormal ABPI at rest and/or DFV scanning. As a result the prevalence of PAD increased by 2%. All patients with an aortoiliac or femoropopliteal obstruction had an ABPI at rest < 0.9. The sensitivity of the combination of the ABPI at rest and the one-minute exercise test to detect abnormal DFV curves was low for crural obstructions., Conclusion: The one-minute exercise test slightly improves the detection of peripheral arterial disease in the general population.

Background: Non-participants can have a considerable influence on the external validity of a study. Therefore, we assessed the socio-demographic, health-related, and lifestyle behavioral differences between participants and non-participants in a comprehensive CVD lifestyle intervention trial, and explored the motives and barriers underlying the decision to participate or not., Methods: We collected data on participants (n = 50) and non-participants (n = 50) who were eligible for inclusion in a comprehensive CVD lifestyle interventional trial. Questionnaires and a hospital patient records database were used to assess socio-demographic, health-related and lifestyle behavioral variables. Univariate and multivariate logistic regression was used to describe the relationship between explanatory variables and study participation. Furthermore, motives and barriers that underlie study participation were investigated by means of questionnaires., Results: Participants were younger, single, had a higher level of education and were employed. No statistically significant differences were found in health measures and behavioral variables. The motives for participation that were most frequently reported were: the perception of being unhealthy and willingness to change their lifestyle. The main barriers reported by non-participants were financial arguments and time investment., Conclusion: The differences between participants and non-participants in a lifestyle intervention trial are in mainly demographic factors. The participants consent in order to alter their lifestyle, and/or because they want to improve their health. To minimize non-participation, it is recommended that access to a lifestyle intervention program should be easy and cause no financial restraints., Trial Registration: ISRCTN69776211.

In this article we present the history of a previously healthy female adolescent, who was seen at our hospital with abdominal pain. This was the result of a large floating thrombus in the aorta. Widespread embolism occurred, which lead to the loss of a limb and a left hemicolectomy. Although our patient is a smoker, used oral contraceptives and was found to have a heterozygote mutation at the factor V Leiden gene, the most important factor contributing to her thrombophilia is thought to be her significantly elevated factor VIII. We stress an aggressive diagnostic and therapeutic approach in young patients with unknown embolism in order to avoid the grave consequences of delay.

Erythermalgia is a rare clinical syndrome characterised by intermittent, usually symmetrical burning pain, warmth and dermal erythema of the extremities with an amelioration of discomfort by cooling of the extremity. In this report, we describe a patient with erythermalgia caused by long-term verapamil use. After discontinuing the verapamil, the symptoms improved dramatically within two weeks.

Background: Recently introduced robot-assisted laparoscopic surgery (RALS) facilitates endoscopic surgical manipulation and thereby reduces the learning curve for (advanced) laparoscopic surgery. We present our learning curve with RALS for aortobifemoral bypass grafting as a treatment for aortoiliac occlusive disease., Methods: Between February 2002 and May 2005, 17 patients were treated in our institution with robot-assisted laparoscopic aorto-bifemoral bypasses. Dissection was performed laparoscopically and the robot was used to make the aortic anastomosis. Operative time, clamping time, and anastomosis time, as well as blood loss and hospital stay, were used as parameters to evaluate the results and to compare the first eight (group 1) and the last nine patients (group2)., Results: Total median operative, clamping, and anastomosis times were 365 min (range: 225-589 min), 86 min (range: 25-205 min), and 41 min (range: 22-110 min), respectively. Total median blood loss was 1,000 ml (range: 100-5,800 ml). Median hospital stay was 4 days (range: 3-57 days). In this series 16/18 anastomoses were completed with the use of the robotic system. Three patients were converted (two in group 1, one in group 2), and one patient died postoperatively (group 1). Median clamping and anastomosis times were significantly different between groups 1 and 2 (111 min [range: 85-205 min] versus 57.5 min [range: 25-130 min], p < 0.01 and 74 min [range: 40-110 min] versus 36 min [range: 22-69 min], p < 0.01, respectively) Total operative time, blood loss, and hospital stay showed no significant difference between groups 1 and 2., Conclusions: Robot-assisted aortic anastomosis was shown to have a steep learning curve with considerable reduction of clamping and anastomosis times. However, due to a longer learning curve for laparoscopic dissection of the abdominal aorta, operation times were not significantly shortened. Even with robotic assistance, laparoscopic aortoiliac surgery remains a complex procedure.

Background: Hyperhomocysteinaemia (HHC) is thought to be a risk factor for cardiovascular disease including heart failure. While numerous studies have analyzed the role of homocysteine (Hcy) in the vasculature, only a few studies investigated the role of Hcy in the heart. Therefore we have analyzed the effects of Hcy on isolated cardiomyocytes., Methods: H9c2 cells (rat cardiomyoblast cells) and adult rat cardiomyocytes were incubated with Hcy and were analyzed for cell viability. Furthermore, we determined the effects of Hcy on intracellular mediators related to cell viability in cardiomyocytes, namely NOX2, reactive oxygen species (ROS), mitochondrial membrane potential (DeltaPsi (m)) and ATP concentrations., Results: We found that incubation of H9c2 cells with 0.1 mM D,L-Hcy (= 60 microM L-Hcy) resulted in an increase of DeltaPsi (m) as well as ATP concentrations. 1.1 mM D,L-Hcy (= 460 microM L-Hcy) induced reversible flip-flop of the plasma membrane phospholipids, but not apoptosis. Incubation with 2.73 mM D,L-Hcy (= 1.18 mM L-Hcy) induced apoptosis and necrosis. This loss of cell viability was accompanied by a thread-to-grain transition of the mitochondrial reticulum, ATP depletion and nuclear NOX2 expression coinciding with ROS production as evident from the presence of nitrotyrosin residues. Notably, only at this concentration we found a significant increase in S-adenosylhomocysteine which is considered the primary culprit in HHC., Conclusion: We found concentration-dependent effects of Hcy in cardiomyocytes, varying from induction of reversible flip-flop of the plasma membrane phospholipids, to apoptosis and necrosis.

A circulation model was created in 6 nonaneurysmal human cadavers to evaluate the deliverability, deployment, and acute performance of a modular branched endograft system for treatment of aortic aneurysms containing essential branch vessels. Two fenestrations were created in an appropriately sized aortic main endograft. Under fluoroscopic guidance, the main endograft was advanced to the target site and the fenestrations were aligned with the ostia of the renal arteries. Branch grafts were placed through the fenestrations into the renal arteries. The outcome was evaluated by post implant angiography and autopsy. Eleven branch grafts were deployed at the target site. All targeted renal arteries showed good patency. At autopsy, all main endografts were adequately deployed, and 10 of 11 branch grafts were locked in place. In this model, deliverability and deployment of the modular branch graft system is feasible in a reliable, predictable, and timely fashion.

Objective: To study the effects on volume expansion and myocardial function of colloids or crystalloids in the treatment of hypovolaemic hypotension after cardiac and major vascular surgery., Design and Setting: A single-centre, single-blinded, randomized clinical trial at the intensive care unit of a university hospital., Patients and Methods: Patients (n=67) were subjected to a 90-min filling pressure-guided fluid challenge with saline 0.9% or the colloids gelatin 4%, hydroxyethyl starch 6% or albumin 5%. Biochemical variables and haemodynamics (transpulmonary thermodilution) were measured., Results: An amount of 1800 (1300-1800) ml of saline or 1600 (750-1800) ml of colloid solution (P< 0.005) was infused. Colloid osmotic pressure (COP) decreased in the saline group and increased in the colloid groups (P< 0.001). Plasma volume increased by 3.0% (-18 to 24) in the saline versus 19% (-11 to 50) in the colloid groups (P< 0.001). Cardiac index increased by median 13% (ns) in the saline group and by 22% in the colloid groups (P<0.005). The rise in left ventricular stroke work index was greater in the colloid than in the saline groups. The different colloids were equally effective. The rise in cardiac index related to the rise in plasma volume and global end-diastolic volume, confirming plasma volume and preload augmentation by the fluid loading., Conclusion: After cardiac or major vascular surgery, the pressure- and time-guided fluid response is dependent on the type of fluid used. Colloid fluid loading leads to a greater increase in preload-recruitable cardiac and left ventricular stroke work indices than that with saline, because of greater plasma volume expansion following an increase in plasma COP.

Surgery for abdominal aneurysm is associated with substantial blood loss. In cardiac surgery, aprotinin, a fibrinolysis inhibitor, has shown to reduce blood loss significantly. Our aim was to assess the effect of aprotinin, when administered during elective surgery of infrarenal abdominal aneurysm, on coagulation, blood loss, and morbidity. A double-blind randomized trial was performed on 35 consecutive patients. They were randomized to either an aprotinin or a placebo group. The aprotinin group received 2,000,000 kallikrein inhibiting units (KIU) of aprotinin (500,000 KIU in 50 mL NaCl 0.9%) as a starting dose, followed by 500,000 KIU per hour during the operation. The placebo group received equal amounts of only NaCl 0.9%. During the operation and 24 hr thereafter, blood samples were taken to assess coagulation factors. Blood loss was measured in suction devices and swabs. All patients were followed until their discharge from the hospital. Statistical analysis was performed by independent t-test or Mann-Whitney U-test and chi-squared test. There was no significant difference in the amount of blood loss or the amount of blood products administered between the two groups. Morbidity and mortality were also comparable. In both groups, consumption of clotting factors could be detected, indicating activation of the coagulation cascade. However, in the aprotinin group, the alpha2-antiplasmin level was raised during surgery, indicating inhibition of fibrinolysis. Administration of aprotinin during elective operations for infrarenal aortic aneurysm induces inhibition of fibrinolysis. However, it does not significantly reduce blood loss or the need for blood products.

Objective: Asymmetric dimethylarginine (ADMA) is a recently identified potent cardiovascular risk factor. ADMA levels are increased in hyperhomocysteinaemia and the metabolism of ADMA is linked with that of homocysteine in several ways. Treatment with B vitamins effectively reduces homocysteine levels, but studies investigating the effect on ADMA levels are scarce and show conflicting results. In this study we evaluated the effect of treatment with B vitamins on ADMA levels in two high cardiovascular risk populations., Methods: In study I, 110 siblings of patients with clinical atherosclerotic disease and postmethionine hyperhomocysteinaemia were treated with 5 mg of folic acid and 250 mg of pyridoxine or placebo, and were analysed after 1 year. In study II, 41 patients with type 2 diabetes and mild hyperhomocysteinaemia were analysed after 6 months treatment with 5 mg of folic acid or placebo., Results: A correlation between baseline homocysteine and ADMA levels was found, which was partly due to confounding by renal function. Homocysteine levels decreased by 43% in study I and by 28% in study II. In both studies, treatment with B vitamins had no effect at all on ADMA, arginine/ADMA ratio and SDMA levels. This result was confirmed in multiple linear regression analyses with adjustment for baseline values and gender., Conclusions: Our studies indicate that B vitamins, despite causing a substantial reduction in plasma homocysteine levels, have no beneficial effect on ADMA levels.

Introduction: We decided to investigate the pathogenesis of pulmonary ventilatory and radiographic abnormalities in patients after major vascular surgery., Patients and Methods: Sixteen mechanically ventilated patients without heart failure were studied, within 3 h after major abdominal surgery. We measured extravascular lung water, intrathoracic, global end-diastolic and pulmonary blood volumes, (67)Ga-transferrin pulmonary leak index and ventilatory and radiographic variables. The latter allowed computation of the lung injury score as a measure of lung injury., Results: The extravascular lung water was elevated (>7 mL kg(-1)) in 5 of 16 patients, while the pulmonary leak index was elevated in 11 patients and a supranormal extravascular lung water was associated with a high pulmonary leak index and higher extravascular lung water relative to intrathoracic blood volume or pulmonary blood volume. Patients were arbitrarily divided into those with a lung injury score >1 and < or =1, and only differed in the factors composing the score as well as in extravascular lung water divided by pulmonary blood volume. A lung injury score >1 was associated with a longer duration of mechanical ventilation., Conclusion: Our data suggest that mild, subclinical, pulmonary oedema is relatively common after major vascular surgery, mainly caused by increased pulmonary capillary permeability in the absence of overt heart failure. However, permeability oedema only partially contributes to postoperative lung injury score and need for mechanical ventilation, suggesting a major contribution by atelectasis.

Background: The role of carotid endarterectomy (CEA) for asymptomatic carotid artery stenosis (aCAS) remains a matter of debate. It seems that not only the degree of stenosis, but also other factors have to be taken in account to improve patient selection and increase the benefit of CEA for aCAS., Methods and Results: The literature pertaining aCAS was reviewed in order to describe the natural history, risk of stroke and benefit of CEA for patients with aCAS in regard to several factors., Conclusion: The benefit of CEA for aCAS is low. Current factors influencing the indication for CEA are severity of stenosis, age, contralateral disease, stenosis progression to >80%, gender, concomitant operations and life expectancy. To improve patient selection investigations will concentrate on plaque characteristics and instability and cerebral hemodynamics and metabolism., (Copyright (c) 2006 S. Karger AG, Basel.)

Purpose: To investigate proximal fixation characteristics of different aortic endograft designs: a suprarenally placed fenestrated endograft, a modular branched endograft, an infrarenal endograft with suprarenal bare stent fixation, and the gold standard, a conventional hand-sewn anastomosis., Methods: Ten human cadaveric aortas were obtained at autopsy and transected 20 mm below the renal arteries to mimic an infrarenal aneurysm neck. In random order, the infrarenal, fenestrated, and branched endografts were deployed into the aorta. Using a hydraulic material testing machine, longitudinal load was applied to the distal end of each endograft until migration occurred, thus defining the displacement force (DF). Subsequently, a hand-sewn infrarenal anastomosis was tested in a similar manner., Results: The median DF was 4.67 N (3.82-6.37) for the infrarenal endograft, 9.17 N (8.03- 10.81) for the fenestrated endograft, and 16.95 N (14.78-19.67) for the branched endograft. The differences in DF between the infrarenal and fenestrated endografts and between the fenestrated and branched designs were statistically significant (both p=0.005). The median force to dislodge the graft from the conventional anastomosis was 89.16 N (71.24-105.23)., Conclusions: Suprarenally placed endografts, especially with additional branch grafts, provide improved proximal fixation compared to an infrarenal endograft with suprarenal bare stent fixation. However, none of the tested endografts approached the optimal, time-proven fixation, the hand-sewn anastomosis.

Objectives: Elucidation of the genetic background of familial abdominal aortic aneurysm (AAA) suggests a genetic etiology., Methods and Results: We carried out a genome-wide scan in three Dutch families with four or five affected siblings. Suggestive loci were further studied by subsequent fine mapping of the locus performed in 101 affected sib-pairs. The genome-wide scan was performed with 400 DNA markers and results were given as non-parametric, multipoint linkage scores (NPL). We observed a suggestive linkage for AAA (NPL score 3.25 at D19S902, 72.72 cM) on chromosome 19q in the three families. After fine mapping on chromosome 19, the NPL score became nominal in the 101 affected sib-pairs. A separate analysis of the three families with fine mapping revealed a peak with significant evidence for linkage (NPL score 3.95 at D19S904, 78.08 cM) on chromosome 19q. This peak was situated to the right compared to the region found in a previously published article for familial AAA on chromosome 19q., Conclusions: Our results identified a candidate locus in three Dutch families with AAA at chromosome 19q13.3. Separate analysis of these three families provides evidence for genetic heterogeneity.