Biomedical subjects

Luigi Pascarella

Publications and source records attributed to Luigi Pascarella.

9 recordsLinked to original sources

PubMed2006

Severe chronic venous insufficiency treated by foamed sclerosant.

Our objective was to chronicle our experience in using sclerosant foam to treat severe chronic venous insufficiency (CVI). Forty-four patients with 60 limbs severely affected by severe CVI were entered into the study. They had lipodermatosclerosis, CEAP 4 (seven limbs); atrophie blanche or scars of healed venous ulcerations, CEAP 5 (18 limbs); and frank, open venous ulcers, CEAP 6 (35 limbs). Patients and limbs were collected into three groups. In group I, all limbs were treated with compression without intervention. Group II consisted of crossover patients who failed compression treatment. Group III consisted of patients treated promptly with sclerosant foam therapy without a waiting period of compression. A standing Doppler duplex reflux examination was done in all cases. Compression was by Unna boot or long stretch elastic bandaging. Foam was generated from Polidocanol 1%, 2%, or 3% by the two-syringe technique and administered under ultrasound guidance. Posttreatment compression was used for 14 days. In addition to clinical and ultrasound evaluation at 2, 7, 14, and 30 days, venous severity scoring was noted at entry and discharge. In group I, 12 patients were discharged from care within 6 weeks of initiating compression. All eight of the class 6 limbs had healed. Group II consisted of four CEAP class 5 limbs and eight class 6 limbs that had failed to heal with compression. Five of eight venous ulcers healed within 2 weeks, two more healed by 4 weeks, and one required 6 weeks to heal. In group III, 7 of 11 venous ulcers healed within 2 weeks and four more within 4 weeks. Venous severity scores reflected the success of treatment, with the greatest change occurring in group III and the least in group I. Limbs treated with foam had a statistically better outcome than those without (p = 0.041). One patient failed foam sclerotherapy, another had pulmonary emboli 4 months after foam treatment, and a single medial gastrocnemius thrombus was discovered 24 hr after treatment. Treatment of severe CVI with compression and foam sclerotherapy causes more rapid resolution of the venous insufficiency complications and does so without an increase in morbidity.

Adult↗

PubMed2005

Lower extremity superficial venous aneurysms.

Venous aneurysms are not rare. But most attention has been paid to deep venous aneurysms. Because of their propensity to thrombose and cause pulmonary embolization. Increased availability of duplex Doppler ultrasound has allowed total evaluation of all venous segments in patients undergoing surgery for chronic venous insufficiency. In this study, patients were recorded consecutively and the venous reflux examination was carried out with the patient standing. The superficial venous system was studied with special interrogation of the great and small saphenous veins and their tributaries. Reflux >0.5 sec was recorded as positive. Data were analyzed using the Spearman's correlation index and the student's t-test. A strong correlation was considered for values of rho > 0.6. A total of 65 superficial venous aneurysms of the saphenous vein systems were found in 43 patients (33 women and 10 men) with an average age of 53 years (range, 34-70). The mean body mass index (BMI) overall was 25 +/- 4.6. The BMI in men was 29.5 +/- 2.5. The BMI in women was 23.6 +/- 4 (p < 0.05). Aneurysms of the saphenous systems were classified into four types. Type I aneurysms (52%) were located in the proximal third of the saphenous vein, not at the saphenofemoral junction but instead just distal to the subterminal valve. Type II aneurysms were located in the shaft of the saphenous vein in the distal third of the thigh (35%). The third classification (type III) of superficial saphenous vein aneurysms was an occurrence of types I and II in the same lower extremity (3 patients/43 patients). Superficial venous aneurysms of the short saphenous system were found and were classified as type IV (6%.) Strong correlations were found with female gender and a very strong correlation of larger aneurysms was found with an elevated BMI in men. There was a so a strong correlation between type III aneurysms of the proximal and distal thigh greater saphenous vein and greater saphenous vein reflux. Aneurysms of the saphenous veins are common and this may have an impact on choice of surgical treatment.

Adult↗

PubMed2005

Venous angiomata: treatment with sclerosant foam.

Venous angiomata, or venous malformations, are often present at birth, although they may not be evident until later. They consist of a spongy tangle of veins, and these lesions usually vary in size. Treatment of venous angiomata is often requested for cosmetic reasons, but painful ulcerations, nerve compression, functional disability can command care. This presentation describes management using sclerosant foam as the treating agent. During a 30-month period ending March 2004, 1,321 patients were investigated for venous disorders at the Vein Institute of La Jolla. Fourteen (incidence 1%) were found to have venous angiomata (: nine women). The age range was 15-76 years (mean 30.8 +/- 18.6). Lesions were classified by the Hamburg system and were primarily venous, extratruncular in 12 patients and combined extratruncular and truncular in two patients. Eight patients, three males, had manifestations of lower extremity Klippel-Trenaunay (syndrome; six had only venous angiomas. Only 10 of the 14 patients were treated. All patients were studied by Doppler duplex examination. Selected lesions were chosen for helical computed tomographic studies. Magnetic resonance venography was also used to image the lesions, define the deep circulation, note connections with normal circulation, identify vessels for therapeutic access, and determine infiltration of the lesion into adjacent soft tissue. Foam was produced by the Tessari two syringes one three-way stopcock teclinique, with the air to Polidocanol ratio being 4 or 5 to 1. This was used at 1% or 2% concentration, specific for each patient. The SonoSite 190 plus Duplex Doppler was used for ultrasound guidance, whenever deep access was required and to monitor progress and effects of treatment. A goal was set for each patient before treatment was begun. Ten patients were treated, and four await treatment. The mean number of treatments was 3.6 +/- 2.8 (range 1-10). A primary goal of pain-free healing was set in patients with nonhealing, painful ulceration or symptomatic varicose veins. This was achieved in all treated patients. Cosmetically, all of the patients were improved, and symptomatic patients were relieved of pain. The single complication was formation of a cutaneous ulcer following injection of telangiectasias. Sclerosant foam is a satisfactory tool to use in treating venous angiomata including the Klippel-Trenaunay syndrome. Use of foam sclerotherapy in this experience has proven the technique to be effective, essentially pain-free, and durable in the short term.

Adolescent↗

PubMed2005

Microcirculation and venous ulcers: a review.

Recent histological and immunocytochemical analyses of venous leg ulcers suggest that lesions observed in the different stages of chronic venous insufficiency (CVI) may be related to an inflammatory process. This inflammatory process leads to fibrosclerotic remodeling of the skin and then to ulceration. The vascular network of the most superficial layers of the skin appears to be the target of the inflammatory reaction. Hemodynamic forces such as venous hypertension, circulatory stasis, and modified conditions of shear stress appear to play an important role in an inflammatory reaction accompanied by leukocyte activation which clinically leads to CVI: venous dermatitis and venous ulceration. The leukocyte activation is accompanied by the expression of integrins and by synthesis and release of many inflammatory molecules, including proteolytic enzymes, leukotrienes, prostaglandin, bradykinin, free oxygen radicals, cytokines, and possibly other classes of inflammatory mediators. The inflammatory reaction perpetuates itself, leading to liposclerotic skin and subcutaneous tissue remodeling. In light of the mechanisms of venous ulcer formation cited above, therapy in the future might be directed against leukocyte activation in order to diminish the magnitude of the inflammatory response. With this in mind, the attention of many investigators has been drawn to two different drugs with an anti-inflammatory effect: pentoxifylline and flavonoids.

Endothelium, Vascular↗

PubMed2005

An animal model of venous hypertension: the role of inflammation in venous valve failure.

BACKGROUND: Clinical observation suggests that chronic venous insufficiency is related to failure of venous valves. Duplex ultrasound studies of lower extremity superficial veins regularly show valve failure and venous reflux. Gross morphologic observation of venous valves in surgical specimens shows tearing, splitting, scarring, and disappearance of valves. HYPOTHESIS: Venous valve damage is acquired, linked with venous hypertension, and affected by inflammation. OBJECTIVE: The objective of this study was to investigate the inflammatory process in valve remodeling associated with acute and chronic venous hypertension. METHODS: A femoral arteriovenous fistula was created in study animals (Wistar rats, n = 60), and animals without an arteriovenous fistula were studied as controls (n = 5). At 1, 7, 21, and 42 days animals with the femoral arteriovenous fistula were anesthetized, and systemic pressure, the pressure in the femoral vein distal to fistula, and the pressure of the femoral vein in the contralateral hind limb were measured. Timed collection of blood backflow after division of the femoral vein distal to the fistula and in the alive, anesthetized animal was collected, measured, and calculated per unit time to be used as an indicator of valve insufficiency. The femoral vein distal to the fistula was harvested; valvular structures were examined and measured. Specimens were processed, and longitudinal sections were made and challenged with immunostaining antibodies against matrix metalloprotease (MMP)-2 and MMP-9. Sections were examined, and expression of molecular markers was determined by light absorption measurements after image digitization. RESULTS: One week after the procedure, all animals exhibited some degree of hind limb edema ipsilateral to the arteriovenous fistula. Pressure in the femoral vein distal to the fistula was markedly increased on average to 96 +/- 9 mm Hg. Reflux was increased in a time-dependent manner, with the 21-day and 42-day groups showing the highest values. Valves just distal to the fistula showed an increased diameter of the valvular annulus and a shortening of the annular height. Venous wall findings included fibrosis and fusion of the media and adventitia and scarring and disappearance of valves principally in the 21- and 42-day specimens. Immunolabeling for MMP-2 showed an increased level in the 21- and 42-day groups. MMP-9 showed an increased level at 1 day, followed by a more marked level in the 21- and 42-day groups. CONCLUSIONS: In this animal model of venous hypertension the findings of limb edema, increasing valvular reflux, and morphologic changes of increased annulus diameter and valve height are seen. Histologic changes included massive fibrosis of media and fusion with adventitia. Inflammatory markers MMP-2 and MMP-9 are strongly represented, and valve disappearance occurs after these markers are present. The gross morphologic changes seen are quite similar to those observed in human surgical specimens removed in treatment of venous insufficiency. CLINICAL RELEVANCE: When observed angioscopically at the time of vein stripping, saphenous vein valves show severe deformities including shortening, scarring, and tearing. The current model of induced venous hypertension demonstrates early venous valve changes that replicate those observed in humans. This observation provides a link from venous hypertension to an induced inflammatory reaction that stimulates the valve damage. Thus the model could be useful for defining the fundamental mechanisms that cause venous valve failure and varicose veins and in pharmacologic testing to prevent or treat venous insufficiency.

Animals↗

PubMed2005

Causes of telengiectasias, reticular veins, and varicose veins.

Study of surgical specimens and direct observation by angioscopy has revealed that the varicose venous wall, the valvular annulus, and the valves themselves undergo profound changes. Morphologic investigations have shown dilation of the valve annulus, bulging valve leaflets, commissural dilation, leaflet stretching, and eventually complete destruction of the valves. The venous wall has been seen to undergo changes of thickening in some segments and thinning in others. Our investigations show that inflammation and subsequent remodeling of the venous valves and wall are the fundamental mechanisms underlying the observed lesions. Hemodynamic forces, such as blood pressure changes in the wall and sheer stress, as well as varying planes of laminar and turbulent flow, induce activation of leukocytes and endothelial cells. Integrins appear to act as intermediaries and expression of adhesion molecules has been observed. Breakdown of extracellular matrix of the media and adventitia through activation of matrix metalloproteases (MMP) has been observed. In particular, expressions of MMP-1, MMP-2, MMP-9, and tissue inhibitor of metalloproteinase have been studied. Telangiectasias, reticular veins, and true varicose veins appear to be a consequence of the changes induced by venous hypertension and sheer stress.

Angioscopy↗

PubMed2005

Severe chronic venous insufficiency: primary treatment with sclerofoam.

Venous insufficiency, for practical purposes, can be divided into primary venous insufficiency and chronic venous insufficiency. The latter is characterized by advanced skin changes of hyperpigmentation, edema, ulceration, scarring from healed ulcers or open ulcerations. These are summarized in the CEAP classification as Classes 4, 5 and 6. Pretreatment evaluation is done with a standing ultrasound reflux examination. Thorough mapping of the extremity reflux is desirable. Physiologic tests of venous function, such as plethysmography, are unnecessary. Treatment is directed at closing refluxing axial veins as well as controlling those perforating veins with outward flow. Varicose veins contribute to axial reflux and must be obliterated. Arterial occlusive disease may complicate venous ulceration in as many as 15% of cases. Initial treatment of severe chronic venous insufficiency is usually carried out by controlling the edema with elastic bandaging or nonelastic support, such as the Unna boot or the CircAid dressing. Surgical intervention has been successful but the advent of foam sclerotherapy has proven to be an attractive alternative to surgery and has added a new tool for the treatment of severe chronic venous insufficiency. In this preliminary experience, the results are quite satisfactory and the technique has been shown to be effective, pain-free, inexpensive, with very little morbidity. Guidelines for obtaining sclerosants for use in foam sclerotherapy legally are provided.

Chronic Disease↗

PubMed2004

Hypertension-induced venous valve remodeling.

INTRODUCTION: In human beings, chronic venous insufficiency is linked to venous hypertension. This in turn is associated with venous valve incompetence. This study was designed to test the hypothesis that venous hypertension serves to initiate a process that results in the venous valve and venous wall damage observed in venous insufficiency. Material and methods Acute venous hypertension was produced by creation of an arteriovenous (AV) fistula between the femoral artery and vein in Wistar rats. At specified intervals pressure in the veins was recorded. The proximal valve containing saphenous vein was exposed, and reflux was measured from reverse blood flow through the first proximal valve. The vein was excised, valve parameters were measured, a portion was taken for morphologic investigation, and the remaining specimen was frozen in liquid nitrogen for investigation of leukocyte infiltration, expression of adhesion molecules, matrix metalloproteinase (MMP) levels, and apoptotic markers. Contralateral nonpressurized saphenous veins were used as control specimens. RESULTS: The saphenous and femoral veins were immediately distended by pulsatile blood flow from the arterial system. Pressure was significantly increased from 11 +/- 2 mm Hg to 94 +/- 9 mm Hg. At 2 days no reflux was detected in the saphenous veins. At 1 week, one of four rats exhibited reflux; at 2 weeks, two of four rats had reflux; and at 3 weeks, three of four rats showed reflux. Contralateral saphenous veins were uniformly competent. Compared with control specimens, the veins were dilated; leaflet length and leaflet width were significantly reduced. Granulocytes, monocytes, and macrophages were identified in all regions of the vein wall, and the number was increased by the presence of the AV fistula. The number of T-lymphocytes was increased, and B-lymphocytes were present. P-selectin was upregulated in the saphenous vein walls, as was intercellular adhesion molecules. MMP-2 and MMP-9 expression in the veins was not enhanced. In the nuclear factor kappabeta family, Ikappabeta was not increased in any hypertensive veins. The number of apoptotic cells in the vein wall was increased in the presence of the AV fistula. CONCLUSION: This study indicates that acute venous hypertension is accompanied by significant venous distention and some valve damage as early as 3 weeks after fistula creation. There is development of inflammatory markers, with leukocyte infiltration and increased adhesion molecule expression. We could not detect significant enhancement of MMP levels or nuclear transcription factors. It is uncertain whether this lack of evidence may be partially due to enhanced apoptosis in venous valves and vein walls. A detailed definition of the inflammatory reaction produced by venous hypertension should be the subject of further study. Clinical relevance Saphenous vein valves when observed at the time of vein stripping show deformities of shortening, scarring, and tearing. The current model of induced venous hypertension demonstrates early venous valve changes similar to those observed in human beings and links them to a venous hypertension-induced inflammatory reaction. Thus the model could be useful in pharmacologic testing to prevent or treat venous insufficiency and for defining the fundamental mechanisms that cause varicose veins.

Animals↗

PubMedDate not supplied

Venous hypertension and the inflammatory cascade: major manifestations and trigger mechanisms.

Recent histologic and immunocytochemical evidence of venous leg ulcers supports the hypothesis that lesions observed at different stages of chronic venous insufficiency may be associated with, and possibly caused by, an inflammatory process. Evidence has been obtained that venous valve deficiency may be associated with leukocyte infiltration into valve leaflets; therefore, it is hypothesized that an essential event in the inflammatory cascade is the enzymatic degradation of the valve leaflets and venous wall. The metalloproteinases (MMP) in veins exposed to elevated pressures up to 6 weeks were examined in a rat femoral fistula model with venous hypertension. Zymography shows increased activity of pro-MMP-2 at 3 and 6 weeks. MMP-2 and MMP-9 activity was predominantly observed at days 7 and 21 after creation of the fistula. The degree of extracellular matrix remodeling correlates with the morphological finding of macroscopic lesions. Therefore, the MMP-2 and MMP-9 activation is already present in veins days after exposure to elevated blood pressure and coincides with periods of early alterations in the valve morphology and early forms of reflux.

Humans↗