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Biomedical subjects

J A Rauwerda

Publications and source records attributed to J A Rauwerda.

At least 19 recordsLinked to original sources

Asymptomatic carotid artery stenosis: past, present and future. How to improve patient selection?

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.

Carotid Stenosis↗

Increased pulmonary capillary permeability and extravascular lung water after major vascular surgery: effect on radiography and ventilatory variables.

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.

Aged↗

No effect of B vitamins on ADMA levels in patients at increased cardiovascular risk.

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.

Adolescent↗

Robot-assisted laparoscopic aortobifemoral bypass for aortoiliac occlusive disease: early clinical experience.

BACKGROUND: Robotic technology may facilitate laparoscopic aortic reconstruction. We present our early clinical experience with laparoscopic aortobifemoral bypass, aided by two different robotic surgical systems. METHODS: Between February 2002 and April 2004, we performed eight robot-assisted laparoscopic aorto-bifemoral bypasses for aortoiliac occlusive disease. All patients were male; median age was 55 years (range: 36-64). Dissection was performed laparoscopically and the robotic system was used to construct the aortic anastomosis. RESULTS: A robot-assisted anastomosis was successfully performed in seven patients. Median operative time was 405 min (range: 260-589), with a median clamp-time of 111 min (range: 85-205). Median blood loss was 900 ml (range: 200-5800). Median anastomosis time was 74 min (range 40-110). In two patients conversion was necessary, one due to bleeding of an earlier clipped lumbar artery after completion of the anastomosis, the other because of difficulties with the laparoscopic exposure of the aorta. On post-operative day 3 one patient died unexpectedly as a result of a massive myocardial infarction. Median hospital stay was 7.5 days (range: 3-57). CONCLUSION: Our initial experience with robotic assisted laparoscopic surgery (RALS) shows it is a feasible technique for aortoiliac bypass surgery. However, laparoscopic aortoiliac surgery demands considerable experience and operative times need to be reduced before this technique can be widely implemented.

Adult↗

Genome-wide linkage in three Dutch families maps a locus for abdominal aortic aneurysms to chromosome 19q13.3.

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.

Aged↗

Endovascular grafting of complex aortic aneurysms with a modular side branch stent-graft system in a porcine model.

OBJECTIVES: To evaluate and refine a stent-graft system with side branches for treatment of aneurysms with essential branch arteries. METHODS: In a porcine model (n=4) supra- and juxta-renal aortic aneurysms were created by suturing an artificial patch onto an anterior aortotomy. Angiography was performed to determine the exact location of the renal arteries. Accordingly, fenestrations were created in an appropriately sized aortic stent-graft. Initial deployment of the aortic graft is partial, whereby the top stent is secured in a cap and distal stents are being restrained, thus ensuring longitudinal and rotational manoeuvrability during alignment of the branch arteries. Separate branch grafts with silicone flanges for connection with the main stent-graft are subsequently placed in the renal arteries followed by full deployment of the main stent-graft. Outcome was evaluated by postoperative angiography and autopsy results and by measuring operating time, blood loss and use of contrast agent. RESULTS: Branched grafts were placed successfully in all trials. The median endovascular procedure time was 126 min (90-160), with 575 ml (400-800) blood loss and 65 ml (50-80) contrast agent use. Angiographically, all aneurysms were excluded without signs of endoleak and all renal arteries were patent. At autopsy, the main stent-graft and all side branches were adequately placed with intact connections between main stent-graft and branch grafts. CONCLUSIONS: In this model, endovascular repair of complex aneurysms using a modular branch graft system is feasible in a reliable, predictable and timely fashion.

Animals↗

Effect of homocysteine-lowering treatment with folic acid plus vitamin B on cerebrovascular atherosclerosis and white matter abnormalities as determined by MRA and MRI: a placebo-controlled, randomized trial.

BACKGROUND: A high plasma homocysteine concentration is an independent risk factor for large and possibly small vessel disease. We investigated the effects of homocysteine-lowering treatment with folic acid plus vitamin B(6) on markers of cerebrovascular atherosclerosis and cerebral microangiopathy. MATERIALS AND METHODS: Using 158 healthy siblings (mean age 46.0 +/- 7.6 years) of patients with premature atherosclerotic disease, we performed a randomized, placebo-controlled trial using 5 mg of folic acid plus 250 mg of vitamin B(6) daily (n = 78) or placebo medication (n = 80). Participants were followed for 2 years with magnetic resonance angiography (MRA) (carotid stenosis; carotid and/or vertebral elongation) and magnetic resonance imaging (MRI) (white matter abnormalities; cerebral atrophy). RESULTS: Seventeen (10.8%) subjects refused MRA/MRI owing to claustrophobia and were excluded. From the remaining 141 participants, 68 received vitamin and 73 received placebo medication [42 (61.8%) and 48 (65.8%) had postmethionine hyperhomocysteinaemia, respectively]. Twenty-four participants (15.2%; 10 in the treatment and 14 in the placebo group) did not complete both years of the trial. Vitamin treatment was associated with an increase in plasma folate (13-fold vs. placebo; P < 0.001) and vitamin B(6) (8.8-fold; P < 0.001). Fasting and postmethionine total homocysteine concentrations decreased 38.7% (95% CI, 27.4-50.0) and 29.1% (95% CI, 19.2-39.0) vs. placebo (all P < 0.001). During follow up six individuals in the vitamin-treated and 11 in the placebo-treated group deteriorated in their outcome measurements. Vitamin treatment, as compared with placebo, was associated with nonsignificantly improved outcomes on both MRA and MRI outcome measurements (odds ratio 0.48; 95% CI 0.17-1.41; P = 0.18 and 0.48; CI 0.14-1.60; P = 0.23, respectively). CONCLUSIONS: These results could indicate a possible favourable effect of homocysteine-lowering treatment on cerebrovascular atherosclerosis and cerebral microangiopathy among healthy siblings of patients with premature atherosclerotic disease, but larger trials are required to establish this with certainty.

Adult↗

Symmetrical, painful ulceration of the lower limbs in a vascular surgery ward: a diagnostic challenge. Pyoderma gangrenosum associated with IgG-kappa paraproteinaemia.

We describe a 61-year-old patient who had been suffering from chronic ulcers of both legs for 18 months. Initially, his condition was diagnosed as ischaemic because of an ankle-brachial index of 0.6, as confirmed by additional angiography. A successful femoro-infragenual bypass procedure was performed, but the ulcers increased in size and number. He was then extensively analysed for a possible (macro)vascular origin of his symptoms. Angiographic analysis of both legs showed no arterial stenosis or occlusion. Despite the extensive experience of the vascular surgeons with leg ulcers, consultations by internal medicine, vascular medicine and dermatology, and tissue examination by our pathologists, pyoderma gangrenosum was not recognised. During a multidisciplinary meeting one of the specialists, to whom the lesions were shown, immediately considered the diagnosis on clinical grounds. The additional finding of IgG-kappa paraproteinaemia and improvement of the ulcers on treatment with corticosteroids were consistent with the diagnosis. Although the majority of patients on the vascular surgery ward have ulcers caused by ischaemia or a combined arterial/venous origin, another (rare) cause, namely pyoderma gangrenosum in association with IgG-kappa paraproteinaemia without the presence of multiple myeloma, should be taken into account.

Chronic Disease↗

The effect of inhibition of renin-angiotensin system by valsartan during hypovolemic shock and low flow sigmoideal ischaemia in pigs.

The aim of this experiment was to study the effect of Renin-Angiotensin System (RAS) blockade by means of valsartan on the colonic and systemic circulation in pigs during low flow sigmoideal ischemia in combination with hypovolemic shock. This condition resembles the situation that occurs in patients suffering from a ruptured aneurysm and a compromised colonic circulation. An experimental study in pigs was performed : 6 pigs with low flow sigmoideal ischemia and hypovolemic shock were treated with valsartan and a control group of 5 pigs with low flow sigmoideal ischemia and hypovolemic shock without medical treatment.Valsartan, 3 mg/kg, was administered intravenously. The operation was performed via left sided lumbotomy. The distal aorta was partially occluded to a flow reduction of 30% of the initial value. Hypovolemic shock was induced by withdrawing 20 ml/kg blood in 45 min. Resuscitation with 30 ml/kg haemaccel was iniated after 2 h of shock. The following parameters were measured: blood pressure, cardiac output; hemoglobin, lactate, angiotensin II in mixed venous blood (obtained from pulmonary artery) and in splanchnic blood (obtained from caudal mesenteric vein); and endoluminal pulse oximetry of the sigmoideal mucosa. Statistical analysis was performed by ANOVA and Wilcoxon signed rank test. There was a significant increase of lactate levels both in systemic and splanchnic circulation (P<0.05) in both groups. In the control group, the mean angiotensin II concentrations in the systemic circulation increased, after induction of ischaemia and shock. In the experimental group, the increase in angiotensin concentrations after resuscitation was significantly more prominent. In the colonic circulation, in both groups, there was a significant increase in angiotensin II levels in the splanchnic circulation following ischaemia and reperfusion (P<0.05), but there was no significant difference between the groups. There were no detectable mucosal signals measured by pulse oximetry after induction of shock throughout the experiment, whereas in the experimental group, median mucosal oxygen saturations of 81, 74.5 and 85% were achieved after resuscitation and declamping (P<0.01).In conclusion, angiotensin II inhibition during hypovolemic shock improves the colonic circulation, measured by pulse oximetry. However, other parameters of tissue ischaemia did not improve.

Angiotensin Receptor Antagonists↗

Endoluminal aortic shunting for distal perfusion during thoracic aortal cross-clamping in a pig model.

PURPOSE OF THE STUDY: To investigate the haemodynamic properties of a direct endovascular aortic shunt to maintain distal aortic perfusion as an alternative of a distal shunt (left-left-, Gott shunt) in thoracic aortic aneurysm repair. METHODS: A shunt was developed and tested in an in vitro model which should be capable of transporting a flow of 3-4 L/min with a decrease in blood pressure < 20 mmHg. Thereupon the shunt was tested in an in vivo experiment in six pigs to assess the possibility of its use with normal distal blood pressure. The shunt was inserted in the thoracic aorta and stayed in place for 1.5 h. Parameters were measured at six time intervals to assess organ perfusion, -function, cardiac output, proximal- and distal blood pressure and aortic- and shunt flow. PRINCIPLE FINDINGS: The mean blood flow through the shunt was 2.5 L/min. The difference of the mean blood pressure over the shunt was on average 14.20 mmHg. Parameters for coagulation disturbance and organ ischaemia were tested. The decrease in mean thrombocyte count was 299-158 (p<0.02). The venous lactate and the venous mesenteric lactate as parameters for intestinal ischemia did not increase significantly. No significant changes occurred in angiotensin II levels. Pulsatile flow was maintained but significantly suppressed (60%) distal from the shunt. The clamp time needed to insert the shunt and the venous mesenteric lactate, as well as the venous lactate, showed high correlation, r(s) = 0.9 (p<0.05) and r(s) = 0.94 (p<0.01). This also accounted for the 2nd clamp time, both r(s) = 0.95 (p<0.05). CONCLUSION: The shunt is capable of transporting a blood flow of 2-4 L/min with an acceptable decrease in distal blood pressure. However, the time, needed to insert the shunt, was significantly associated with parameters of organ ischaemia.

Anastomosis, Surgical↗

Homocysteine-lowering treatment with folic acid plus vitamin B6 lowers urinary albumin excretion but not plasma markers of endothelial function or C-reactive protein: further analysis of secondary end-points of a randomized clinical trial.

BACKGROUND: Hyperhomocysteinaemia is an independent risk factor for atherosclerosis and is thought to induce its effects through causing endothelial dysfunction. We studied the effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on urinary and plasma markers of endothelial function, and on plasma C-reactive protein, a marker of chronic inflammation. DESIGN: We performed a placebo-controlled 2-year trial among 158 healthy siblings of patients with premature atherosclerotic disease to determine the effect of daily folic acid (5 mg) plus vitamin B6 (250 mg) treatment as compared with placebo medication (n = 80) on markers of endothelial function (urinary albumin-to-creatinine ratio and plasma concentrations of soluble E-selectin, soluble vascular cell adhesion molecule-1, von Willebrand factor, tissue-type plasminogen activator and plasminogen activator inhibitor-1) and inflammation (C-reactive protein). Outcome variables were assessed at baseline and after 1 and 2 years of treatment. RESULTS: Fasting homocysteine concentrations ( micromol L-1) at baseline and after treatment were 14.7 +/- 8.2 and 7.4 +/- 1.9 in the vitamin and 14.7 +/- 8.8 and 12.0 +/- 5.4 for the placebo group, respectively. Vitamin treatment was associated with a decreased urinary albumin-to-creatinine ratio at follow up [regression coefficient (beta) -0.20 mg mmol-1 (CI: -0.43-0.03); P = 0.09]. After adjustment for age, sex, baseline concentrations of postmethionine total homocysteine plus the baseline albumin-to-creatinine ratio, the beta was -0.23 mg mmol-1 (CI: -0.43 to -0.02; P = 0.03), which amounts to a decrease of approximately 20%. There was no apparent effect of vitamin treatment on the other markers. CONCLUSIONS: Homocysteine-lowering vitamin treatment in healthy siblings of patients with premature atherosclerotic disease is associated with a decreased urinary albumin-to-creatinine ratio, but not with other markers of endothelial dysfunction, or in plasma C-reactive protein. The clinical significance of these findings remains to be determined.

Adult↗

Genetic linkage of candidate genes in families with abdominal aortic aneurysms?

OBJECTIVES: to examine possible involvement of several candidate genes in the aetiology of familial abdominal aortic aneurysm (AAA). DESIGN: after reviewing the literature on the genetics of familial AAA, betaine homocysteine methyltransferase (BHMT), collagen type Ialpha2 (COL1A2) and cathepsin H (CTSH), were selected as potential candidate genes, which influence structure, strength, elasticity and mechanical resistance of the aortic wall. MATERIALS: forty-eight families with 110 family members and AAA were included in the affected sib-pair analysis. One large family of three generations was analysed separately because in this family also other clinical symptoms were involved. METHODS: genetic linkage analysis was performed with DNA markers in the region of BHMT, COL1A2 and CTSH. RESULTS: In the overall sib-pair analysis, the LOD scores for BHMT, COL1A2 and CTSH were 0.7, 0.2 and -0.7, whereas in the large family these numbers were -0.6, -2.2 and -2.7, respectively. CONCLUSIONS: none of the candidate genes selected showed a suggestive linkage with AAA. Exclusion of the COL1A2 and CTSH genes was possible in the large family that was analysed separately.

Aortic Aneurysm, Abdominal↗

The impact of training in unselected patients on mortality and morbidity in carotid endarterectomy in a vascular training center and the recommendations of the European Board of Surgery Qualification in Vascular Surgery.

PURPOSE: To investigate the impact of training of vascular fellows on the results of carotid endarterectomy (CEA) in unselected patients and to evaluate the recommendations of the European Board of Surgery Qualification in Vascular Surgery (EBSQ-VASC) concerning CEA. METHODS: Complication rates and selection criteria of all CEAs, performed between 1995 and 2000 (n = 200) were retrospectively analysed and correlated to operating surgeon; supervised, nonsupervised vascular trainees, and consultant vascular surgeons. The number of CEAs were compared with the required minimal procedures according to the EBSQ-VASC. RESULTS: Selection criteria for CEA did not differ significantly between operating surgeon groups, except that combined procedures were more performed by nonsupervised trainees and asymptomatic stenosis by consultant surgeons. The overall persistent disabling stroke rate and stroke-related mortality was 3%, with 4.3% in the supervised group, 0% in the unsupervised, and 2.8% in the consultant surgeon group, respectively. The amount of CEAs corresponded to the demands of the EBSQ-VASC. CONCLUSIONS: In our institution, no significant differences in neurological morbidity and mortality following CEA could be demonstrated in relation to surgeon training level. The number of CEAs performed by residents fulfill the criteria of the EBSQ-VASC. We conclude that CEA can be safely taught to vascular trainees in unselected patients in a vascular training centre.

Adult↗

The liver is an important organ in the metabolism of asymmetrical dimethylarginine (ADMA).

BACKGROUND AND AIMS: Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase enzymes, whereas symmetrical dimethylarginine (SDMA) competes with arginine transport. Although both dimethylarginines may be important regulators of the arginine-NO pathway, their metabolism is largely unknown. Both dimethylarginines are removed from the body by urinary excretion. However, ADMA is also subject to enzymatic degradation by the enzyme dimethylarginine dimethylaminohydrolase (DDAH), which is highly expressed in the liver. To elucidate the role of the liver in the metabolism of ADMA, we aimed to investigate dimethylarginine handling of the liver in detail. METHODS: Ten male Wistar rats were used for this study. Blood flow was measured using radiolabeled microspheres according to the reference sample method. Concentrations of dimethylarginines were measured by HPLC. The combination of arteriovenous concentration difference and organ blood flow allowed calculation of net organ fluxes and fractional extraction rates. RESULTS: Both the liver (0.89+/-0.11) and the kidney (0.68+/-0.06) showed a high net uptake (nmol/100 g body weight (BW)/min) of ADMA, whereas a significant net uptake of SDMA was only observed in the kidney (0.34+/-0.04). For the liver, fractional extraction rates were 29.5% +/-3.0 for ADMA and 0.0%+/-3.7 for SDMA. Fractional extraction rates of ADMA and SDMA for the kidney were 36.0%+/-2.7 and 31.6%+/-3.8, respectively. CONCLUSIONS: The liver plays an important role in the metabolism of ADMA by taking up large amounts of ADMA from the systemic circulation.

Animals↗