Colour duplex scanning and phlebography in deep vein thrombosis.

Clinical evaluation of deep venous thrombosis is often unreliable. Recently it has been shown that deep venous thrombosis may be detected with colour duplex scanning which is safer than phlebography. However it is not clear how colour duplex correlates with phlebography. One hundred and twenty consecutive patients with suspected deep vein thrombosis were studied by colour duplex scanning and phlebography to compare the two methods. Both tests were positive in 102 limbs and negative in 16 limbs. In two cases of below-knee thrombosis colour duplex was negative while phlebography showed small localised thrombosis. The sensitivity of colour duplex was 98%, its specificity and positive predictive value 100% and its negative predictive value 88.8%. In conclusion colour duplex appears to be as effective as phlebography in detecting deep venous thrombosis above knee.

Skin blood flux and the venoarteriolar response in the perimalleolar area in patients with venous hypertension.

In patients with venous hypertension due to postphlebitic syndrome or varicose veins skin changes, liposclerosis and ulcerations are associated with increased skin blood flux at rest, a decreased venoarteriolar response and increased capillary filtration. Using laser-Doppler flowmetry we studied skin flux and the venoarteriolar response in the perimalleolar region in 100 normal limbs, 100 limb with varicose veins and 100 postphlebitic limbs with edema, skin changes and liposclerosis. The venoarteriolar response was studied with the leg on dependency, the foot being 50 cm below heart level. Flux at rest and on dependency were increased and the venoarteriolar response decreased in both groups of patients at a significantly greater extent in postphlebitic limbs. In conclusion laser-Doppler flowmetry measurements differentiate between normal limbs and those with venous hypertension and between postphlebitic limbs and limbs with venous hypertension due to varicose veins. The increase in skin flux and decrease in venoarteriolar response may be useful to define and quantify the degree of microangiopathy and the effects of treatments in venous hypertension.

Evaluation of cerebral blood flow in premature newborns by duplex scanning using a high resolution probe.

The evaluation of cerebral blood flow in premature newborns offers interesting information about cerebral circulation and, physiological flow variations. Using a high resolution probe as the Access 10 of the ATL ultramark 4 duplex scanner it was possible to define flow in the anterior cerebral artery and in the middle cerebral artery in newborns without significant pathology. This study was performed in premature babies both to evaluate the best technical solution to study these small arteries and to define a standard of flow to be used in future evaluations. By the 10 MHz focus (on the variable focus probe 5-7.5 and 10 MHz) it was observed that a smaller variation of flow determinations is obtained by the 10 MHz focus (both for the middle and anterior cerebral arteries). In conclusion duplex scanning offers probably the best solution to evaluate cerebral blood flow in premature newborns both in qualitative and quantitative way.

Laser-Doppler flowmetry in the assessment of "mild" Raynaud's phenomenon and its treatment.

Raynaud's phenomenon is characterised by a reduction in skin temperature and blood flow. Laser-Doppler Flowmetry (LDF) has been used to evaluate LDF recovery time after immersion of hands in water at 20 degrees C for 1 minute before and after treatment. After treatment for 4 weeks with nifedipine 10 mg b.i.d. the recovery time was again measured. The study showed that the treatment is useful for normalising the recovery times and reducing symptoms.

Laser-Doppler flux in the normal and atherosclerotic carotid artery wall in normotensive and hypertensive subjects.

UNLABELLED: The aim of this study was to evaluate in vivo the perfusion of the arterial wall in normal sections of the carotid artery, in sections with fibrotic plaques and in sections with plaques and heavy calcifications using laser-Doppler flowmetry. Patients with carotid plaques undergoing carotid endarterectomy were studied. Using intraoperative ultrasound three different levels of atherosclerosis involvement of the arterial wall were defined: normal arterial wall where all components (intima, media and adventitia) were clearly separated and intact; wall with intima-media thickening and fibrotic plaques (no calcification); sections with diffusely calcified plaques. In 20 patients 20 normal sections, 20 sections with fibrotic plaques and 20 sections with large plaques and heavy calcifications were studied. Diabetic patients were excluded. Also the carotid wall of 10 patients with essential hypertension were evaluated. Wall flux was measured on the external surface of the common carotid artery before endarterectomy. Measurements were recorded when at least 3/4 of the adventitia was intact for a lenght of at least 4 cm. RESULTS: The average flux in normal sections was higher (p < 0.05) than in sections with fibrotic plaques and in sections with calcified plaques. A significant difference in flux (p < 0.05) between fibrotic (decreased flux) and calcified areas (very low flux). In hypertensive subjects flux measurements were significantly lower than in non-hypertensive patients (p < 0.05). In conclusions a higher wall perfusion was observed in normal arterial sections in comparison with sections with plaques. Sections with calcifications and large plaques had a markedly low flux. In hypertensive subjects all sections had a significantly lower flux.

Skin flux and the venoarteriolar response in essential hypertension.

Vasoconstriction is considered an important factor in patients with hypertension. The presence of skin flow reduction and the decrease in the venoarteriolar response (the skin flow decrease due to postural changes such as standing of lowering the leg below heart level) were studied in normal subjects and in patients with essential hypertension with laser-Doppler flowmetry. Measurements were repeated after a period of four weeks treatment with nifedipine. Laser-Doppler skin flux when the patient was resting supine and with the foot 50 cm below heart level was significantly lower than in normals. Also the venoarteriolar response was significantly reduced in hypertensives. After nifedipine treatment a significant increase in skin flux and improvement of the venoarteriolar response were observed. In conclusion laser-Doppler flowmetry can be used in hypertensives to quantify skin flow reduction, the altered venoarteriolar response and possibly the effects of drugs on the microcirculation.

Non-invasive ultrasonic biopsy in the classification of early arterial lesions and in the evaluation of the rate of progression of arteriosclerosis.

The evaluation of early arterial lesions and the follow-up of the progression of arteriosclerotic wall changes is possible with high resolution ultrasound. While dynamic (duplex scanning) data are suitable for the follow-up of advanced stenosis and plaques, the morphological evaluation performed using the technique of non-invasive ultrasonic biopsy may be used to follow-up early lesions and their progression. The data obtained by ultrasonic biopsy are related to the incidence of occult coronary ischemia and to the occurrence of cardiovascular events in 4 years. The rate of progression (ROP) to the next, more advanced UB class can be also evaluated by ultrasonic biopsy. It has been shown that in diabetic and hyperlipidemic subjects the ROP is higher. Also in interventional studies using lipid lowering agents (with a four-year follow-up) a reduction in ROP in treated asymptomatic hyperlipidemic subjects in comparison with controls has been documented. The combination of dynamic data and morphological data gives us a complete evaluation of the vascular system both for the assessment of single individuals and for large population studies.

Treatment of intermittent claudication with defibrotide or mesoglycan. A double blind study.

Forty-four patients with intermittent claudication were included and randomised in two groups respectively treated with oral defibrotide (one 400 mg tablet bid) or oral mesoglycan (one 24 mg tablet bid) for 6 months. Twenty-two subjects completed the study in the defibrotide group and 20 in the mesoglycan group. The two treatments were well tolerated and the two drop outs in the mesoglycan group were not due to medical causes. In the defibrotide group, after 1 month the pain-free walking distance (PFWD) increased from 473 +/- 96 m to 586 +/- 84 (p < 0.05). The walking distance (WD) increased from 767 +/- 125 m to 898 +/- 109 (p < 0.05). After 6 months the posterior tibial pressure (PTP) at the end of the treadmill exercise test also increased from 40 +/- 19 to 63 +/- 12 (p < 0.05). No variations in PFWD, WD and PTP were observed in the mesoglycan group. The improvement in walking was possibly due to the action of defibrotide increasing local fibrinolysis and decreasing the distal vasospasm present in subjects with peripheral vascular disease and intermittent claudication.

Clinical evaluation of defibrotide in the treatment of arterial and venous vascular disease. A preliminary report.

Defibrotide is a new compound with antithrombotic and profibrinolytic activity. It increases the endogenous fibrinolytic activity by promoting the cellular activator of plasminogen from endothelial cells and by decreasing the concentration of its inhibitors. In this study we evaluated a total of 223 patients for a mean period of 43 days for the following vascular conditions: (a) superficial venous thrombosis; (b) prophylaxis against deep venous thrombosis; (c) peripheral vascular disease (ischaemic foot and intermittent claudication; (d) prophylaxis against TIAs in patients with carotid plaques determining embolization; (e) treatment of venous ulcerations determined by chronic venous incompetence; (f) patients with Raynaud's phenomenon and disease. The tolerability observed was good. No side effects were observed even in more prolonged treatments. The overall efficacy was good for all groups especially in comparison with other treatment already in use for these vascular conditions. In conclusion defibrotide is a particularly useful drug in these vascular diseases and can be used both for acute and chronic treatments.

Inter/intra-observer variability of carotid and femoral bifurcation intima-media thickness measurements.

Arterial wall thickening may be quantitatively assessed by measuring the intima-media thickness (IMT) with high resolution ultrasound. Previous studies have shown a good inter/intraobserver variability of IMT measurements in the common carotid. In this study we evaluated the inter/intraobserver variability of IMT measurements in 10 randomly selected asymptomatic subjects (age 55.4 +/- 6). Two carotids and two femorals were studied in each subject. IMT for each patient was the average of five IMT measurements at the artery bifurcation. Three observers repeated the scanning and the measurements twice with no knowledge of the previous readings. The between observer coefficient of variation (CV) was 8.45%; the intraobserver CV (mean of carotids and femorals) varied from 4.4 to 5.1% for the three observers who measured IMT three times. The mean absolute difference between the first and the third measurement was 0.0738 mm. In conclusion IMT measurement variability is mostly due to differences between observers. The intraobserver variability is very small. IMT measurements at the carotid and femoral bifurcations have a low variability and are a good expression of atherosclerosis as they consider early lesions at the bifurcation level which may not be observed in the common carotid.

The edema tester in the evaluation of swollen limbs in venous and lymphatic disease.

BACKGROUND: Edema is a common condition in most venous and lymphatic diseases. The ACI edema testers (ET) have been developed to objectively evaluate the presence of edema. Two types of testers have been developed. ET1 is a soft plastic plate (5 x 2 cm) characterised by two parallel protrusions while the ET2 is characterised by two lines of 7 holes. METHODS: The ETs are applied onto the internal perimalleolar region with the protrusions/holes in contact with the skin. A blood pressure cuff is applied over the area (pressure maintained at 50 mmHg for a period between 1-3 minutes). When the cuff is removed, with the ET1 skin marks are usually just visible in normal limbs (they disappear in a few minutes). We studied 22 normal limbs, 19 with varicose veins, 22 with chronic venous insufficiency, 5 with primary lymphedema and 8 with severe chronic lymphedema. RESULTS: In limbs with severe edema the whole length of the protrusions is visible; with moderate edema only a part of the protrusions is visible. With the ET2 skin marks are just visible in normal limbs (only the larger holes). Marks disappear in a few minutes in normal limbs while in limbs with edema the number of visible holes is increased (in severe edema all holes are visible). There were significant differences between normals and patients (considering skin mark length, number of visible holes and disappearance times). CONCLUSIONS: The two testers separated patients with different severity of edema due to chronic venous or lymphatic problems. In severe lymphatic problems all parameters were different (p < 0.02) from those observed in venous disease. A reproducibility study indicated that the ET tests have minimal variations in mark visibility or length or hole numbers (for the ET2).

Laser Doppler skin perfusion pressure in normal and vascular subjects with rest pain: an universal measurement?

Laser-Doppler (LDF) skin perfusion pressure was measured and compared with Doppler ankle pressure measurements in 40 normal subjects and 20 patients with rest pain and ankle/foot Doppler pressure lower than 70 mmHg. Six different, commercially available LDF instruments were used. To obtain perfusion pressure a standard blood pressure cuff was used measuring the pressure at which the skin flux reading reached the biological zero level when inflating the cuff (P1) and the pressure at which the LDF tracing reappeared after deflating the cuff from sovrasistolic pressure level (P2). Perfusion pressure (PP) was considered to be the average [P1 + P2]/2. No differences in PP amongst the 6 instruments both in normal and vascular subjects were observed. These results indicate that PP is an universal LDF measurement which can be easily obtained with different LDF instruments.

Microcirculation in high perfusion microangiopathy.

Using laser-Doppler flowmetry in association with other noninvasive microcirculatory techniques such as transcutaneous PO2 and PCO2 and capillary filtration measurements it is possible to define two major types of microangiopathy. Low perfusion microangiopathy (LPM) is observed in peripheral vascular disease, essential hypertension, Raynaud's disease etc. High perfusion microangiopathy (HPM) is observed in venous hypertensive microangiopathy and diabetic microangiopathy. In both these conditions there is an increased skin flux, decreased venoarteriolar response and increased capillary filtration leading to edema formation. In HPM elastic compression and drugs acting on capillary filtration effectively reduce skin flux and the increased capillary leakage and edema formation.

Delayed arteriosclerosis progression in high risk subjects treated with mesoglycan. Evaluation of intima-media thickness.

Noninvasive ultrasonic biopsy (UB) can be used to classify arteriosclerotic lesions and their progression in the carotid and femoral bifurcation. Also the evaluation of intima-media thickness (IMT) is useful to quantify the progression of early arteriosclerosis. Two randomly selected groups of asymptomatic subjects were included in a 18 month, open study. One group was treated with oral mesoglycan (200 mg/day) and one group was followed-up as control. The two groups were comparable for age and sex distribution. The average UB score was 14.4 +/- 5 in the treatment group and 14.3 +/- 8 in the control group. After 18 months the UB score was 15.7 +/- 4 in the treatment and 16.2 +/- 6 in the control group. These differences were not significant. However the average increase in IMT in 18 months in the treatment group was 0.016 mm equivalent to 0.0106 mm per year. In the control group the average increase was 0.119 equivalent to 0.0793 per year. Therefore the increase in IMT was 7.48 times greater in the control group. These differences were significant (p < 0.05). Two drop-outs were recorded in the treatment group and 1 in the control group. In conclusion IMT measurements showed a decreased level of IMT progression in subjects under mesoglycan treatment. These results need to be confirmed by a larger randomised study.

Microcirculatory effects of elastic stockings in diabetic microangiopathy: a 24-week study.

Patients with diabetic microangiopathy were studied by laser-Doppler flowmetry--measuring skin blood flux at rest (RF) and the venoarteriolar response (VAR) and evaluating the rate of ankle swelling (RAS) to study capillary filtration. After randomisation, 38 patients were treated for 24 weeks with below-knee elastic stockings, and 36--acting as controls--were left without elastic compression. After 12 and 24 weeks, there were no significant changes in the control group, while there was a significant improvement of the microcirculatory parameters in patients using stockings. RF (increased at the beginning of the study) was significantly decreased, the VAR (impaired at the beginning of the study) improved significantly and the abnormally increased capillary filtration decreased. Elastic stockings seem to be useful in diabetic microangiopathy improving microcirculatory parameters and decreasing capillary filtration and oedema. These effects may improve diabetic microangiopathy and possibly slow down its rate of progression.

Noninvasive tests in venous insufficiency.

Chronic venous insufficiency (CVI) is the result of outflow obstruction, reflux or a combination of both. Noninvasive tests detect an quantify obstruction and reflux if present and define the anatomic localisation of the abnormality. In evaluating CVI noninvasive tests combine physiologic and imaging techniques. These tests are widely available, simple, quick and cost-effective and therefore they are the methods of choice for initial objective evaluation. Different tests provide answers to different questions. The optimum clinically useful information can be now obtained using only three instruments: pocket Doppler, duplex or color duplex scanner and air plethysmography. The value of ambulatory venous pressure, photoplethysmography and light reflection reography, air plethysmography, duplex and color duplex scanning to assess reflux and the value of tests to assess out-flow obstruction are presented. Pooled data collected from large studies are also presented for reference. Qualitative and quantitative assessment of CVI are useful both for clinical assessment and to evaluate the effect of treatments.

Subclinical arteriosclerosis screening. The PAP/PEA study. Prevalenza dell'Arteriosclerosi Precoce (Prevalence of Early Arteriosclerosis).

Noninvasive screening of subclinical atherosclerosis is possible with ultrasonic biopsy (UB) performed with high resolution ultrasound scanning. Five UB classes have been identified, each class corresponding to a different incidence of cardiovascular events (CVE) in 4 years and silent coronary ischemia (SCI). In a study including 2230 asymptomatic subjects 3 risk groups were defined. In the low risk group (class I and II; 82.01% of the population sample) the incidence of CVE and SCI was zero. These subjects may be seen again after 3 years. In the moderate risk group (class II and IV; 13.3%) monitoring and early intervention may be needed. In the high risk group (class V; 4.6%) prophylaxis or treatment may be necessary. The screening is effective, simple and may be organised at very low cost--i.e. 30.000 asymptomatic subjects may be scanned at the cost of 100.000 ECU. Each scan, including carotid and femoral bifurcations, may be performed in 15 minutes. In our communities this cost is equivalent to the average cost of a single major stroke or major coronary ischemic event in a working adult aging between 45 and 60. Organization problems and the fragmentation of competences has prevented the evolution of atherosclerosis screening. The problem can be solved organising a network including epidemiologists, angiologists and cardiovascular surgical centres where all phases of atherosclerosis may be studied and detected, progression prevented and complications treated with a global vision of the disease.

Ultrasonic classification of carotid plaques causing less than 60% stenosis according to ultrasound morphology and events.

Carotid plaque morphology studied by ultrasound has been used to classify 3 types of bifurcation plaques, producing less than 60% stenosis on duplex scanning: Type A, the homogeneous, highly echogenic plaque; Type B, the heterogeneous (mainly echogenic, B-1 or mainly echolucent, B-2) plaque; Type C, the complex plaque with irregular surface, echogenic and/or echolucent with calcifications. One hundred asymptomatic subjects in each plaque group were included in a prospective 4-year follow-up study to evaluate clinical events and brain damage by yearly cerebral CT and MR scans. After four years 96 subjects with type A plaque, 89 with type B-1 and 67 with type C plaques completed the study. While there were no clinical events or positive cerebral scans in subjects with type A plaques there was a significantly increasing number of cerebral and vascular events in subjects with plaque B and C type with a zero mortality in the plaque A group, a 2.24% mortality in type B plaques and a significantly higher (p > 0.05) mortality (13.4%) in type C plaques. CT and MR scans revealed brain damage which had been totally asymptomatic with MR detecting a larger number of lesions. Also the number of cerebral lesions observed by CT/MR were significantly greater than the number of recorded clinical episodes. ECG stress test revealed a larger number of asymptomatic coronary disease in the C type plaques. In conclusion ultrasound plaque morphology is linked to different incidences of cerebral and cardiac events, brain damage and asymptomatic coronary disease. Also CT and MR may reveal lesions which do not cause signs or symptoms.

Ocular and retrobulbar blood flow in ocular hypertensives treated with topical timolol, betaxolol and carteolol.

The purpose of this study was to evaluate the effect of topical timolol 0.5%, betaxolol 0.5% and carteolol 2% on the blood flow velocity of the central retinal artery (CRA), the posterior ciliary artery (PCA) and the ophthalmic artery (OA) in patients with ocular hypertension. A group of 14 patients with ocular hypertension and a group of 11 normals were studied. The color Doppler was used to measure the peak systolic flow velocity (PSFV) and the end diastolic flow velocity (EDFV) of the CRA, the PCA and the OA in the normals and in the patients. The normals were under no treatment, while the patients were studied before and after treatment with topical timolol 0.5%, betaxolol 0.5% and carteolol 2%. In the systolic phase, there was a significant increase in the flow velocity of the CRA with all three drugs. In the diastolic phase of the CRA, the increase was significant for timolol 0.5% and carteolol 2% but not for betaxolol 0.5%. The flow velocity of the PCA and OA remained unchanged. In this study of 14 patients with ocular hypertension, topical timolol 0.5%, betaxolol 0.5% and carteolol 2% led to a significant increase in the flow velocity of the CRA without creating a steal or decrease in the flow velocity of the PCA.

Doppler ultrasonography in giant cell arteritis.

A patient with biopsy negative giant cell arteritis was examined and treated by our group. Since in some cases the visual loss in this disease is due to a central retinal artery occlusion, a technique to evaluate the blood flow velocity in this artery would be useful. The Duplex scanner was utilized by us in this patient to study the blood flow velocity of the central retinal artery. The flow velocity was reduced. The patient was treated with systemic steroids which lead to clinical and symptomatic improvement. After the treatment with steroids the Duplex scanner was again used to study the flow velocity of the central retinal artery. The blood flow velocity improved. We think that Doppler ultrasonography may be useful in the diagnosis of and in monitoring the treatment of some cases of giant cell arteritis.