Platelets and cytokines in concert with endothelial activation in patients with peripheral arterial occlusive disease.

We tested the hypothesis whether circulating oncostatin-M (OSM), a cytokine that in vitro promotes fibrinogen biosynthesis and smooth muscle cell proliferation, or soluble CD40 ligand (CD40L; CD154), a leukocyte and platelet surface marker that stimulates endothelial cells, were associated: (a) with fibrinogen and other soluble cell adhesion molecules, such as P-selectin, vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 and platelet-endothelial cell adhesion molecule-1; or (b) with restenosis and platelet activation in 71 patients with peripheral arterial occlusive disease undergoing peripheral angioplasty (PTA). Platelet membrane activation markers (CD62P, CD63, activated GPIIb/IIIa) were immunologically measured at 0, 1, 24 and 48 h, and 3 and 6 months after PTA. Soluble cell adhesion molecules, endothelial markers and various hemostatic variables were measured before PTA. Of the patients, 42.3% developed restenosis within 6 months, defined as a >50% reduction of the lumen at the site of balloon dilatation. Soluble CD40L was not higher in the restenosis group. Interestingly, patients with high CD40L showed significantly higher soluble VCAM-1 (P < 0.01) and thrombomodulin (P < 0.01), as well as trends for higher soluble P- and E-selectin. Platelet activation was found uniformly increased mostly at 1 and 24 h, as well as at 3 and 6 months. OSM was measurable in 53.5% (6.9 +/- 9.4 pg/ml) of the patients and undetectable in the others. No differences in the rate of restenosis was found in these two groups, which did not differ with respect to fibrinogen (3.14 +/- 1.00 versus 3.21 +/- 0.70 g/l), or the other parameters. In conclusion, soluble CD40L is associated with higher endothelial biological markers that might implicate its involvement in endothelial activation. Platelet activation, probably intermittent, might play a significant role through the expression of CD40L as a source of activation signals to the endothelial cells. Free circulating OSM does not seem to correlate directly with fibrinogen or with other acute phase reaction proteins, the synthesis of which it could influence in vitro. This might well not mean, however, that OSM lacks this activity in vivo.

Noninvasive mapping of lower limb arterial lesions.

Thirty patients with peripheral arterial disease were evaluated using an ultrasonic duplex scanner. A total of 338 arterial segments from the level of the iliac to the popliteal artery were studied and compared with the results of arteriography read independently by two radiologists who were unaware of the results with the scanner. The results demonstrate that this method is not only suitable for clinical use but is as good as arteriography in defining both the location and extent of the arterial involvement.

Computer based pattern recognition of carotid artery Doppler signals for disease classification: prospective validation.

A computer based pattern recognition method has been developed to classify the percent diameter reduction in nonoccluded internal carotid arteries. Using a combined B-mode/pulsed Doppler unit, the system utilizes spectral waveforms obtained from the low common and proximal internal carotid artery locations. The ECG-R wave is used as a time reference to synchronize the averaging of Doppler spectra from 20 heart cycles. An averaged waveform is generated and represents the spectral data from which features are extracted for analysis. A stepwise selection algorithm identifies a feature subset for partitioning the entire range of disease into two states, less than and greater than a decision point. Three such partitions are made, leading to the following categories: Normal, 1-20, 21-50 and 51-99% dia. reduction. A classifier was trained, tested prospectively against unknown data and the results compared to angiography. Of the 170 vessels tested, 141 (82%) were classified in the same category by angiography and the computer system. Agreement for each category was 93% (27/29) for the normals, 81.5% (44/54) for the 1-20% lesions, 78% (29/37) for the 21-50% lesions and 82% (41/50) for the 51-99% lesions. The computer method and angiography differed by more than one category in only one of the 170 tests. The level of agreement corrected for chance (Kappa +/- SE(K] was 0.769 +/- 0.039. Future efforts will be directed toward dividing classification of disease further (especially in the 51-99% category), developing a dedicated microprocessor for on-line analysis of the signals and using the system for prospective epidemiological studies of various populations.

Assessment of collateral perfusion: a pharmacodynamic study with buflomedil hydrochloride.

The aim of the study was to assess the influence of Buflomedil hydrochloride on collateral function. Ten patients with isolated superficial femoral occlusions were investigated twice by duplex sonography with measurement sites at the common femoral artery (CF) and the popliteal artery (PA). After the second scan 200 mg of Buflomedil hydrochloride were infused; the infusion was followed by a third duplex examination. Endpoints assessed included the arterial diameter (D(CF), D(PA)), the systolic peak velocity (Vmax), the mean velocity of the maximum envelope (Vmean m.e.), the intensity weighted time average mean velocity (Vmean i.w.), the maximum reverse flow velocity (Vrev), the end-diastolic velocity (Venddiast), the calculated volume flow (Q), the pulsatility and the resistance indices (PI, RI), and PI and RI based segmental damping factors (DF(PI), DF(RI)). For the CF measurement site the infusion of Buflomedil hydrochloride resulted in a significant reduction in Vrev and PI (p<0.05), whereas trends in the opposite direction (increase) were observed for both measures of Vmean and for Q (0.1

Doppler-based diagnosis of restenosis after femoropopliteal percutaneous transluminal angioplasty: sensitivity and specificity of the ankle/brachial pressure index versus changes in absolute pressure values.

The aim of this study was to investigate the sensitivity and specificity of changes of the ankle/brachial pressure index (ABI) and changes in absolute ankle pressure values to detect restenosis in patients who underwent femoropopliteal percutaneous transluminal angioplasty (PTA). In total, 171 patients were followed up prospectively for 12 months; sensitivity and specificity of Doppler-based diagnosis were calculated with duplex scanning as the gold standard. The criteria for restenosis were: (1) a loss of 50% of the ABI increase or (2) loss of 50% of the absolute ankle systolic pressure, gained by PTA. For both criteria, different cut-off points (minimum increase of ABI or ankle pressure gained by PTA) were evaluated. The overall sensitivity and specificity of the ABI criterion was 67% and 80%, respectively. The introduction of cut-off points (the minimum ABI increase gained by PTA), ranging between > or = 0.13 and > or = 0.35, did not markedly improve the results. The overall sensitivity and specificity of the absolute ankle pressure criterion again was poor (59% and 81%). With the introduction of cut-off points (the minimum increase of absolute ankle pressure gained by PTA) ranging between > or = 15 mm Hg and > or = 20 mm Hg, the sensitivity and specificity of the criterion improved to acceptable 92% and 96%, respectively. It is concluded, that in the long-term follow-up of PTA patients, the "loss of 50% ankle pressure" criterion will detect restenosis with reasonable accuracy in those patients, in whom an increase in systolic ankle pressure > or = 20 mm Hg is warranted.

The pre-stenotic Doppler shift signature.

In two series of measurements the Doppler shift signatures of 10 healthy volunteers were studied at varying distances proximal to a total reflection site, in order to describe parameters which are predictive for downstream lesions. Characteristic changes both in amplitude and time parameters were found; the most marked changes being the abolishment of a DC-component for monophasic signatures, the development or the augmentation of early diastolic reverse flow amplitudes together with a highly significant reduction in the signatures' systolic deceleration time. Maximum changes however tended to be localized at 2 to 4 centimeters upstream from the reflection site. Further upstream propagation was limited. Hence the time course of a Doppler signature and particularly its systolic deceleration should be taken into account in addition to the known resistance indices, if downstream lesions shall be predicted from upstream Doppler signatures. The limited upstream propagation of pre-stenotic Doppler signature changes restricts its diagnostic value to vascular segments where the region adjacent to a lesion is routinely scanned; thus diagnostic benefit can be expected for extracranial carotid artery disease but hardly for peripheral (lower limb) lesions.

Symptomatic vascular complications after vascular closure device use following diagnostic and interventional catheterisation.

BACKGROUND: Haemostatic puncture closure devices for rapid and effective hemostasis after arterial catheterisation are a comfortable alternative to manual compression. Implanting a collagen plug against the vessel wall may become responsible for other kind of vascular injuries i.e. thrombotic or stenotic lesions and peripheral embolisation. The aim of this paper is to report our clinically relevant vascular complications after Angio-Seal and to discuss the results in the light of the current literature. PATIENTS AND METHODS: We report the symptomatic vascular complications in 17 of 7376 patients undergoing diagnostic or therapeutic catheterisation between May 2000 and March 2003 at the University Hospital Basel. RESULTS: Most patients presented with ischaemic symptoms, arterial stenoses or occlusions and thrombotic lesions (n = 14), whereas pseudoaneurysms were extremely rare (n = 3). Most patients with ischaemic lesions underwent vascular surgery and all patients with a pseudoaneurysm were successfully treated by ultrasound-guided compression. CONCLUSIONS: Severe vascular complications after Angio-Seal are rare, consistent with the current literature. There may be a shift from pseudoaneurysms to ischaemic lesions.

[Unilateral swelling of the leg]. / Die einseitige Beinschwellung.

Unilateral swelling of the leg is a common problem in general practice. The spectrum of underlying diseases is broad and does include venous and lymphatic disorders but also less frequent diseases such as Baker cysts and Sudeck's dystrophia. In the majority of cases a diagnosis can be made based on the patients history, the clinical findings and some specific laboratory and/or instrumental investigations. Selected cases however, require the attention of the vascular specialist.

[Ambulatory therapy in varicose veins]. / Die ambulante Therapie der Varikose.

The treatment of varicose veins comprises conservative and active options. Every patient with varices has to be informed on the conservative modalities and should apply them in daily life. Compression therapy, as the most important part of the conservative treatment, should be considered individually for any patient according to the varicose-type, the grade of chronic venous insufficiency and the compliance of the patient. Active treatment modalities are clearly indicated in varices with complications such as trophic skin changes, varicophlebitis or when varices cause pain. But the cosmetic problem should not be underestimated. Morphologic and hemodynamic information obtained by noninvasive duplex technique allows the individualization of the surgical strategy for each patient. Besides surgical techniques used being less and less traumatic (invagination stripping, stab evulsion phlebectomy), more and more interventions are realized under ambulatory conditions in local anesthesia, even crossectomy with partial stripping of truncal varices. More important and complex operations, interventions involving more than one saphenous vein or reinterventions in recurrent varices are still performed under hospital conditions. They require only a short hospitalization time (2 to 4 days). Considering this very favourable evolution in surgery with a net trend to ambulatory, thus more economic treatment, the indications for sclerotherapy--a traditionally ambulatory modality with high recurrence-rate--are limited to reticular varices and telangiectasies.

["Arteriosclerotic" aneurysm of the abdominal aorta]. / "Arteriosklerotisches" Aneurysma der Aorta abdominalis.

We present a patient with an aortic aneurysm and the epidemiology, etiology, screening, symptoms and therapeutic options of abdominal aortic aneurysms are discussed. A widening of the abdominal aorta >3 cm is termed aortic aneurysm. As patients with aortic aneurysm are mostly oligosymptomatic until rupture occurs and an estimated 30,000 patients annually die from ruptured aortic aneurysm in the US a screening of the population at greatest risk (smokers, familial predisposition) is recommended. Screening is best done by ultrasound. Noninvasive therapy is limited to antiplatelet therapy and optimal adjustment of risk factors. For definitive treatment endovascular aortic repair (EVAR) is considered an established alternative to open surgery with lower 30 days mortality but higher reintervention rate.

[Check-up, what else?]. / Check-up, was sonst?

Evidence-based check-up does not only include medical history and physical examination but consultation with regard to recommended vaccinations, screening for cancer and cardiovascular risk factors. Patients with PAD are at high risk for cardiovascular events but frequently claudication is not mentioned during anamnesis, thus specific attention to exercise-dependent leg discomfort is necessary. Recognition of PAD related symptoms is important because it may implicate secondary cardiovascular prevention and specific therapeutic options including walking exercise and endovascular revascularisation exist.

["Good Morning, Doctor, I'm Flying to Australia Next Week!"]. / "Herr Doktor, ich fliege nächste Woche nach Australien!"

Travel-related venous thromboembolism (VTE) is probably less frequent than previously suspected and becomes relevant when a flight lasts eight hours or more. Usually, general measures such as avoiding constrictive clothing or dehydration and doing gymnastics and walking around in the cabin are sufficient for preventing VTE. Compression stockings can be recommended when risk factors for VTE are present. Low molecular weight heparins in prophylactic dosage should be considered after previous VTE.

Venous reflux and venous distensibility in varicose and healthy veins.

OBJECTIVES: The aim of this study was to analyse venous diameter changes and venous reflux parameters, assessed during a standardised Valsalva manoeuvre in healthy subjects and in patients with varicose veins. METHODS: Measurements were carried out in 444 vein segments, (96 legs of 48 healthy volunteers, 52 legs of 35 patients with varicose veins). The common femoral vein (CVF), the femoral vein (FV) and the great saphenous vein (GSV) were investigated. The parameters of reflux and the relative venous diameter change (VD diff %) were measured simultaneously during a standardised Valsalva manoeuvre. RESULTS: Venous diameter changes during Valsalva manoeuvre (VD diff) were significantly greater in the GSV and in the deep veins of varicose patients compared to healthy subjects. The median (Interquartile range) of VD max in the CFV was: 13.1 (3.5) mm and 11.2 (3.4) mm (p=0.0002, Mann-Whitney - U test), in the FV 7.8 (2.7) mm and 6.9 (2.0) mm (p=0.01, Mann-Whitney), in the GSV: 7.3 (3.7) mm and 4.2 (1.1) mm (p<0.0001, Mann-Whitney) for the varicose and healthy veins respectively. Good correlation was seen for the retrograde peak reflux velocity (PRV) and VD diff % in varicose veins (r=0.71 (0.57 - 0.81) p<0.0001, Mann-Whitney). CONCLUSION: Relative venous diameter--changes during a standardised Valsalva manoeuvre are significantly larger in the deep and superficial veins of varicose vein patients compared with healthy veins, the increased distensibility correlates with venous reflux parameters in varicose vein patients.

[Acute ischemia after intraarterial drug injection]. / Akute Ischämie nach intraarterieller Drogeninjektion.

HISTORY AND CLINICAL FINDINGS: A 36-year-old patient presented with a severe hand ischemia after intraarterial injection of four dissolved tablets of Methylphenidate each 10 mg (Ritalin into the right radial artery. INVESTIGATIONS: Non-invasive vascular diagnostic demonstrated a normal perfusion of the radial and ulnar artery and a severe ischemia of the small vessels of the right hand. TREATMENT AND COURSE: Under suspicion of a combined vaso-spastic and thromboembolic arterial occlusion we started an intraarterial lysis therapy followed by anticoagulation with heparin and infusions of prostaglandines. Despite this therapy necroses of three fingers developed; partial amputation was followed by a good wound healing. CONCLUSIONS: Ischemia of an extremity after intraarterial injection of drugs is a vascular emergency.

[Venous cross-sectional area: measured or calculated?]. / Venenquerschnittsfläche: messen oder berechnen?

AIM: The aim of this study was to compare measured versus calculated venous cross-sectional area in healthy subjects in a standing and a lying position with normal breath-ing and during Valsalva manoeuvre. METHOD: Measurements were carried out in 30 venous segments (the common femoral vein CFV, the superficial femoral vein SFV, the greater saphenous vein GSV) of 5 healthy volunteers (4 female, 1 male) with a median age of 28.7 years (range 23.4-46.7 years) in supine and standing position, while normally breathing and during a standardised Valsalva manoeuvre. Venous diameters were measured from B-mode in longitudinal view while cross-sectional areas were planimetrically assessed from transverse B-mode as recorded on video (S-VHS). The mathematical calculation of areas followed the formula (0.5 diameter)2 x pi. All investigations were performed 3 times; mean values from these 3 measurements were used for further computation. Measurements were performed using the NIH Image 1.6 program. RESULTS: Correlation coefficients r of the calculated versus the measured venous area while normal breathing in standing and in lying subjects were: 0.92 and 0.82 in the CFV, 0.92 and 0.84 in the SFV as well as 0.98 and 0.97 in the GSV, respectively. During Valsalva manoeuvre in standing and lying subjects the correlation coefficients r amounted to: 0.94 and 0.93 in the CFV, 0.92 and 0.94 in the SFV as well as 0.99 and 0.98 in the GSV, respectively. CONCLUSIONS: In healthy volunteers measured and calculated venous cross-sectional area at rest and during Valsalva manoeuvre correlate well. Correlation is numerically better in standing compared to lying subjects while normal breathing. Calculated venous area is accurate and can be used for further calculations.

Prospective 12-year follow-up study of clinical and hemodynamic sequelae after deep vein thrombosis in low-risk patients (Zürich study).

BACKGROUND: No prospective study of the long-term sequelae of more than 10 years after acute deep vein thrombosis exists so far. Therefore, 58 low-risk patients with DVT were included in a prospective study to evaluate the natural history of postthrombotic syndrome. METHODS AND RESULTS: Clinical and hemodynamic examinations were performed at the time of admission; after 3, 6, and 12 months; after the 2nd, 3rd, 4th, 5th years; and finally after the 12th year. All patients received heparin initially and oral anticoagulants subsequently. After 12 years, 64% of the patients exhibited normal findings. Mild skin changes were found in 28%, marked trophic changes in 5%, and only one venous ulcer occurred. Regular use of compression stockings was reported by 54% of the patients with multilevel thrombosis. Although mean maximum venous outflow was significantly reduced from the acute event to 12 years later (P<.003) compared with the contralateral leg, a significant (P<.05) improvement was observed 6 months later. Recanalization of calf vein thrombosis was detected by Doppler sonography after 3 months. Sixty-four percent of the multilevel thromboses were recanalized completely or in part after 1 year; in 69%, valvular incompetence was found. CONCLUSIONS: In contrast to earlier reports, this prospective study up to 12 years after deep vein thrombosis demonstrates a low incidence of postthrombotic syndrome by administration of oral anticoagulants and regular compression therapy. However, the adverse clinical event rate (mortality 14%) and a recurrence rate of 24% show that the prognosis after deep vein thrombosis does not appear favorable even in low-risk patients.

[Prospective 12-year follow-up study of clinical and hemodynamic sequelae of deep venous thromboses in patients with low risk (Zurich Study)]. / Prospektive 12-Jahres-Verlaufsstudie über klinische und hämodynamische Folgen tiefer Venenthrombosen bei Patienten mit niedrigem Risiko (Zürich-Studie).

No prospective study of the long-term sequelae of more than 10 years after acute deep vein thrombosis exists so far. Therefore, 28 patients with DVT were included in a prospective study to evaluate the natural history of postthrombotic syndrome. Clinical and hemodynamic examinations were performed at the time of admission; after 3, 6 and 12 months; after the 2nd, 3rd, 4th, 5th; and finally after the 12th year. All patients received unfractionated heparin initially and oral anticoagulants subsequently. After 12 years, 64% of the patients exhibited normal findings. Mild skin changes were found in 28%, marked trophic changes in 5%, and only 1 venous ulcer occurred. Regular use of compression stockings was reported by 54% of the patients with multilevel disease. Although mean maximum venous outflow was significantly reduced from the acute event to 2 years later (p < 0.003) compared with the contralateral leg, a significant (p < 0.05) improvement was observed 6 months later. Recanalization of calf vein thrombosis was detected by Doppler sonography after 3 months. 64% of the multilevel thromboses were recanalized completely or in part after 1 year; in 69%, valvular incompetence was found. In conclusion, in contrast to earlier reports, this prospective study up to 12 years after DVT demonstrates a low incidence of PTS by administration of initially unfractionated heparin, oral anticoagulation and compression therapy. However, the adverse clinical event rate (mortality 14%) and recurrency rate of 24% show that the prognosis after DVT does not appear favorable even in low-risk patients.

Cuff-compression of the proximal calf to reduce venous contamination in contrast-enhanced stepping-table magnetic Resonance angiography.

PURPOSE: To minimize venous overlay at the calf station in contrast-enhanced three-dimensional (3D) stepping-table magnetic resonance angiography (MRA) using a continuous cuff-compression technique during MR data acquisition. MATERIAL AND METHODS: Within 14 months, 32 patients suffering from symptomatic peripheral arterial occlusive disease (PAOD) with a bilateral ankle-brachial index (ABI) of 0.8 or below were consecutively enrolled in this study. Unilateral cuff-compression of the proximal calf was applied in the study group (n = 14). The control group (n = 18) underwent no compression. All patients underwent three-step 3D contrast-enhanced magnetic resonance angiography (3D CE-MRA) according to the institute's protocol. Venous contamination scores (vcs) at the calf station were blindly ranked by a 1 to 3 rating score (3 = major venous contamination). The vcs values of the control group were regarded as standard. Statistical significance between both groups was evaluated with a paired t test. RESULTS: Symmetric venous contamination was observed within the control group with a mean vcs of 2.2+/-0.6 on the left side and 2.2+/-0.7 on the right side with deltavcsleft-right of 0.1+/-0.2 (P>0.1). In the study group, asymmetric venous contamination was determined with vcsmean = 2.3+/-0.6 for the uncompressed side and vcsmean =1.4+/-0.5 for the compressed side and a deltavcsuncomp-comp of 0.9+/-0.5 (P<0.00005). The control group and the uncompressed side of the study group showed no significant difference in venous contamination (P > 0.1). CONCLUSION: Subdiastolic cuff-compression of the proximal calf is an easily applicable and inexpensive technique by which to reduce venous contamination of the calf station in stepping-table MR angiography and to improve evaluation of the infrapopliteal arteries.

A new rotational thrombectomy catheter: system design and first clinical experiences.

PURPOSE: To describe a new catheter for the percutaneous mechanical removal of fresh and organized thrombi, and to assess its efficacy and safety in vitro and in vivo. METHODS: The catheter consists of a coated stainless steel spiral that rotates at 40,000 rpm over a guidewire inside the whole length of an 8 Fr, single-lumen, polyurethane catheter, driving a dual-blade cutting crown. Abraded occlusion material is sucked into the catheter head through distal side holes and transported by the spiral into a reservoir at the proximal end. The efficacy of the device was tested in arterial models and fresh bovine carotid arteries (n = 72). In a clinical pilot study 10 patients (8 women, 2 men; mean age 70.6 +/- 10.1 years) with occlusions of the superficial femoral artery (2-12 cm, mean 5.8 cm), not older than 4 weeks, underwent thrombectomy with the new catheter. RESULTS: In arterial models and bovine cadaver arteries the catheter completely removed fresh thrombi. Occlusion material of higher consistency was cut into particles of 100-500 micron and transported outside. Thrombectomy was successful and vessel patency restored in all 10 patients. The ankle/brachial pressure index significantly (p < 0.0005) increased from 0.41 +/- 0. 18 before intervention to 0.88 +/- 0.15 after 48 hr and to 0.84 +/- 0.20 after 3 months. Two reocclusions occurred within 14 days after the intervention. CONCLUSION: Thrombectomy with the new device appears to be feasible and safe in patients with acute and subacute occlusions of the femoropopliteal artery.