A Toe Flexion NIRS assisted Test for Rapid Assessment of Foot Perfusion in Peripheral Arterial Disease: Feasibility, Validity, and Diagnostic Accuracy.

OBJECTIVES: Feasibility, validity, and diagnostic accuracy of a non-invasive dynamic ambulatory test were assessed with near infrared spectroscopy (NIRS) evaluating foot perfusion in peripheral arterial disease (PAD). METHODS: This was a prospective observational study. Eighty PAD patients (63 males, 71 ± 9 years), including 41 patients with coexisting diabetes, participated. Thirteen healthy subjects (8 males, 26 ± 8 years) were also studied by echo colour Doppler providing 160 diseased and 26 non-diseased limbs. Under identical clinostatic conditions, participants performed a 10-repetition toe flexion tests with NIRS probes on the dorsum of each foot; the area under the curve of the oxygenated haemoglobin trace ("toflex area") was calculated and the ankle-brachial index (ABI) was measured. Time of execution, rate of wrong tests, and adverse reactions were recorded. Within session reliability was assessed by administering the test twice, with a 5 minute interval between tests. The validity was assessed determining whether the toflex area was (a) dependent on the oxygen delivery from the lower limb arteries simulating PAD conditions by a progressive blood flow restriction (40-120% of systolic pressure) in healthy subjects; (b) consistent with the degree of PAD ranked by ABI and correlated with ABI and ankle pressure values in PAD patients. The diagnostic accuracy in detecting PAD was compared with examination using echo colour Doppler ultrasound. RESULTS: All tests were rapidly, satisfactorily (<1% mistakes), and safely performed. Toflex area values, superimposable in the two sessions (intra-class correlation coefficient 0.92), were comparable to PAD values following blood flow restriction, consistent with PAD severity, correlated with dorsal pedis artery pressure (r = .21; p = .007) and ABI (r = .65; p < .001) in PAD, but not in the presence of diabetes. Toflex area was similar to echo colour Doppler for detecting PAD following receiver operating characteristic curve analysis (area = 0.987, p < .001; toflex area values ≤ -28 arbitrary units, sensitivity/specificity 95.6/100). CONCLUSION: The toe flexion test enables ambulatory assessment of foot perfusion and PAD detection, even in the presence of non-measurable ABI or diseases affecting the microcirculation.

Very Early Carotid Endarterectomy After Intravenous Thrombolysis.

OBJECTIVE/BACKGROUND: The timing of carotid endarterectomy (CEA) after thrombolysis is still a matter of debate. The aim of this study was to analyse a cohort of patients undergoing urgent endarterectomy after intravenous thrombolysis for acute ischaemic stroke. METHODS: This was an observational study. Prospective databases were reviewed and matched to identify patients who underwent CEA early after intravenous thrombolysis (2009-14). The focus was carotid surgery performed within 12 hours of stroke onset in patients with a high grade (≥70%) symptomatic carotid stenosis, associated with vulnerable plaques or stroke in evolution, and evidence of a significant salvageable ischaemic penumbra on perfusion computed tomography scan. Demographic and clinical information, as well as data on relevant outcomes were extracted. RESULTS: Thirty four consecutive stroke patients who underwent CEA within 2 weeks of thrombolysis for acute ischaemic stroke and ipsilateral high grade carotid stenosis were identified. In 11 patients the surgical procedure was performed within 12 hours of the onset of symptoms. All patients showed a clinical improvement after combined treatment. The 3 month outcome was favourable (modified Rankin Scale ≤ 2) in 10 patients. No haemorrhagic complications were registered. There was neither peri-operative stroke nor stroke within 3 months of surgery. One patient died from acute myocardial infarction 3 days after intervention. CONCLUSION: This experience suggests that very early CEA after thrombolysis, aimed at removing the source of potential embolisation and restoring blood flow, may be safe and can lead to a favourable outcome.

Ultrastructure of internal jugular vein defective valves.

OBJECTIVES: To study the ultrastructure of intraluminal defects found in the internal jugular vein by using a scanning electron microscopy. METHODS: Using a scanning electron microscopy, intraluminal septa and/or defective valves blocking the flow in the distal internal jugular vein of seven patients were studied together with the adjacent wall and compared with control specimen. RESULTS: The internal jugular veins' wall showed a significant derangement of the endothelial layer as compared to controls. Surprisingly, no endothelial cells were found in the defective cusps, and the surface of the structure is covered by a fibro-reticular lamina. CONCLUSIONS: Although the lack of endothelial cells in the internal jugular vein intraluminal obstacles is a further abnormality found in course of chronic cerebrospinal venous insufficiency, our investigation cannot clarify whether this finding is primary or caused by progressive loss of endothelium in relation to altered haemodynamic forces and/or to a past post-thrombotic/inflammatory remodelling.

A dynamic objective evaluation of peripheral arterial disease by near-infrared spectroscopy.

OBJECTIVES: Near-Infrared Spectroscopy (NIRS), suitable for dynamic measurements, is not routinely used for peripheral arterial disease (PAD). We propose a dynamic NIRS-based measurement to quantify variations in muscle metabolism in PAD. METHOD: Sixty-seven consecutive PAD patients (males=56, age 71.6+/-8.7 years) and 28 healthy subjects (males=12, age 30.4+/-11.9 years) were studied. An echo-colour Doppler (ECD) was performed and the ankle-brachial index (ABI) was calculated. Participants performed an incremental treadmill test with NIRS probes on the gastrocnemius. Variations in oxygenated (HbO(2)), deoxygenated (HHb), total (tHb=HbO(2)+HHb), and differential (dHb=HbO(2)-HHb) haemoglobin were recorded and quantified as area-under-curve (AUC) within the range 1.7-3.0 km h(-1). Heart rate was recorded, and the number of beats in the same interval was calculated (dHr). RESULTS: O(2)Hb(AUC), HHb(AUC) and dHb(AUC) differed between diseased and non-diseased legs (P<0.0001) and exhibited different patterns related to PAD severity according to the ABI value. A compensatory heart rate increase was observed in PAD patients. Compared with the ECD positivity for occlusions/stenoses or multiple plaques, only the receiver-operating characteristic (ROC) analysis of dHb(AUC) (area=0.932, P<0.0001) showed a sensitivity/specificity of 87.6/93.4 for values

Inflammation in venous disease.

Chronic venous disease (CVD), mainly due to venous reflux or, sometimes, to venous outflow obstruction, produces a microcirculatory overload leading to the impairment of venous drainage. Venous drainage depends primarily on a major hemodynamic parameter called trans-mural pressure (TMP). TMP is increased in patients affected by CVD, leading to impaired tissue drainage, and, consequently, facilitating the beginning of the inflammatory cascade. Increased TMP determines red blood cell extravasation and either dermal hemosiderin deposits or iron laden-phagocytes. Iron deposits are readily visible in the legs of all patients affected by severe CVD. Local iron overload could generate free radicals or activate a proteolytic hyperactivity of metalloproteinases (MMPs) and/or downregulate tissue inhibitors of MMPs. These negative effects are particularly evident in carriers of the common HFE gene's mutations C282Y and H63D, because intracellular iron deposits of mutated macrophages have less stability than those of the wild type, inducing a significant oxidative stress. It has been demonstrated that such genetic variants increase the risk of ulcers and advance the age of ulcer onset, respectively. The iron-dependent vision of inflammation in CVD paves the way to new therapeutic strategies including the deliberate induction of iron deficiency as a treatment modality for non-healing and/or recurrent venous leg ulcers. The inflammatory cascade in CVD shares several aspects with that activated in the course of multiple sclerosis, an inflammatory and neurodegenerative disease of unknown origin in which the impairment of cerebral venous outflow mechanisms has been recently demonstrated.

Primary intravascular synovial sarcoma of the femoral vein in a male patient, case report.

Synovial Sarcoma (SS) is an aggressive neoplasm commonly affecting deep soft tissues of the extremities. In rare instances SS can arise in large veins of the lower extremities or trunk. We report the first case of intravascular synovial sarcoma (IVSS) occurring in a male patient. A biphasic tumor was diagnosed by histology and immunohistochemistry. Molecular analysis at RNA level confirmed the diagnosis demonstrating the chromosomal translocation t(X;18) (p11.2;q11.2) in the tumor. Although extremely rare, IVSS should be considered in the differential diagnosis of primary intravascular neoplasms and as a potential cause of deep vein thrombosis and thromboembolism.

Double right bronchial artery aneurysm treated with combined procedures.

PURPOSE: Bronchial artery aneurysms occur rarely. We present an unusual case. CASE REPORT: We present a patient with double right bronchial artery aneurysms that were treated with a combination of endovascular and surgical procedures. CONCLUSION: This case report illustrates the treatment options for this unusual problem.

Speed rather than distance: a novel graded treadmill test to assess claudication.

OBJECTIVE: To evaluate a new treadmill test, determining pain threshold speed (PTS) for use in assessment and measuring rehabilitation of patients with intermittent claudication. METHODS AND DESIGN: Twenty-nine patients with claudication were evaluated, and the ankle-brachial index (ABI) was assessed. PTS was determined with a treadmill protocol based on level walking, low starting speed, and progressive increments at a predetermined distance up to the onset of pain. Repeatability and equivalence with a time-based protocol were verified. PTS was compared to pain-free walking distance, 6-minute walking distance, and ABI. RESULTS: PTS was measured in all patients (3.6+/-1.1 km/h). Repeatability and equivalence between established tests were demonstrated. PTS showed a significant correlation with pain-free walking distance (r=0.833; P=0.0001), with 6-minute walking distance (r=0.724; P=0.005), and with ABI in the more ischemic limb (r=0.641; P=0.0001). CONCLUSIONS: PTS is a reliable parameter that correlates well with other established measures. It is useful for determining the degree of functional handicap and for designing and guiding rehabilitation protocols.

Training guided by pain threshold speed. Effects of a home-based program on claudication.

AIM: To verify the effectiveness of a 120 day home-based program guided by the pain threshold speed (PTS). METHODS: Twenty-nine patients with stable claudication were measured for ankle pressure (AP), ankle-brachial index (ABI), PTS, maximal speed (Smax) on treadmill. Daily walking sessions at a speed 20-30% below PTS were prescribed. Determination of the training speed was supervised and facilitated at home. The program included a daily record of exercise data and symptoms, an intermediate PTS re-evaluation to adjust the training speed, and the reassessment of all the parameters after 120 days. RESULTS: Overall patients showed a reduction of systemic blood pressure (151.3+/-14.3 to 147.6+/-18.3 mmHg; 77.1 +/-9.1 to 72.4+/-8, p=0.008) while AP did not. ABI increased from 0.65+/-0.13 to 0.71+/- 0.18 (p=0.01). PTS and Smax rose from 3.2+/-1.1 to 4.2+/-1.5 km/h (p=0.0001) and from 3.9+/-1.3 to 4.6+/-1.3 km/h (p=0.0001), respectively. According to their compliance, patients were divided into 3 groups: 1) trained (T, n=14): exercise at the prescribed speed, 2) free-walkers (FW, n=7): walking speed markedly below PTS and 3) untrained (U, n=8): incomplete program compliance. T group showed symptom reduction up to pain disappearance. The ABI change (0.72+/-0.09 to 0.82+/- 0.16, p<0.02) was correlated to AP increase (r= 0.879). PTS and Smax rose from 3.6+/-1.1 to 5.4+/-0.8 km/h (p<0.02) and from 4.7+/-1.2 to 5.7+/-0.7 (p<0.02), respectively. FW showed improvement of all parameters, and U a better walking efficiency. CONCLUSIONS: In patients with claudication, a low-cost home-based program driven by PTS allows dramatic improvements of functional parameters.

[Effectiveness of the combination of alpha tocopherol, rutin, melilotus, and centella asiatica in the treatment of patients with chronic venous insufficiency]. / Efficacia clinica di un'asociazione di alfatocoferoli, rutina, meliloto e centella asiatica nel trattamento di pazienti con insufficienza venosa cronica.

BACKGROUND: The aim of this comparative clinical study was to evaluate the efficacy of the association of alphatocopherol, rutin, melilotus officinalis, and centella asiatica with oral administration in patients with chronic venous insufficiency. METHODS: Thirty patients with chronic venous insufficiency have been randomized in two groups of fifteen subjects (control and treatment group). During the period of treatment the patients didn't wear elastocompressive stockings. The therapeutic efficacy and the clinical tolerability of this association have been valued with clinical-instrumental evaluations and by a control after 15 and 30 days. Functional bothers, cramps and the edema have been valued in function presence and of their gravity with a clinical-score between 0 and 4. RESULTS: At the end of the observation period, a significant improvement of the clinical simptomatology was obtained, characterised by a diminution of the sovrafascial edema. CONCLUSIONS: The present study confirms previous clinical experiences regarding the described treatment and suggests its application in chronic venous insufficiency.

Aneurysm dissection of the extracranial internal carotid artery.

Aneurysm of the extracranial internal carotid artery is a rare event. This is a pathology with an elevated mortality of 70%. The most important etiologic factor is atherosclerosis. Here we report a case of surgically treated extracranial internal carotid artery (ICA) aneurysm. A 77-year-old man noticed a laterocervical pulsatile mass. Color Doppler ultrasonography revealed an ICA aneurysm related to a parietal thrombosis. The ICA aneurysm was confirmed by intra-arterial digital subtraction angiography, and cerebral computer tomography (CT) was negative. Surgical treatment reconstruction with the interposition of a part of the great saphenous vein was indicated. Exploration of the aneurysmatic wall revealed a posterolateral dissection. In this paper are discussed clinical and therapeutic implications.

[Aorto-mesenteric compression syndrome. Description of clinical case and critical review of the literature]. / La sindrome del compasso aorto-mesenterico. Descrizione di un caso clinico e revisione critica della letteratura.

Aorto-mesenteric duodenal compression syndrome is a rare disease in which superior mesenteric artery causes a substenosis of the duodenum. Pathogenesis of this syndrome is due to congenital or acquired factors. Symptomatology is usually non specific and intermittent. Diagnosis is given by selective superior mesenteric artery angiography. Therapy is only surgery.

Intraoperative H/R echography for carotid surgery.

BACKGROUND: Intraoperative duplex examination can be used during carotid surgery to identify small technical defects (like anastomotic stenosis, intimal flaps or subintimal wall dissections) that cannot be easily found by palpatory manoeuvres. The objective of this clinical study is to correlate intraoperative duplex findings with early postoperative complications and with duplex data obtained during follow-up. METHODS: From January 1993 to January 1996 we compared early and late postoperative complications that occurred after carotid surgery in two groups of patients: a group of 120 patients undergone intraoperative duplex compared with a group of 100 patients not undergone intraoperative ultrasound. RESULTS: The percentages of early and late postoperative complications which occurred in the first group were respectively 7.5% and 4.2% contrary to 10% and 7% occurred in the control group. CONCLUSIONS: Duplex constitutes a selective intraoperative method for carotid surgery, easy to use, enable to identify and immediately correct technical defects.

Effects of vasoactive agents in healthy and diseased human saphenous veins.

PURPOSE: Smooth muscle reactivity is one of the factors involved in the pathogenesis of varicose veins. We investigated the myotropic effects of the 3 main vasoconstrictor agents norepinephrine (NE), angiotensin II (Ang II), and endothelin-1 (ET-1) in isolated human saphenous veins. METHODS: Human saphenous veins were collected from 23 patients with primary chronic venous insufficiency who underwent elective varicose vein resections and who were stratified into the following 3 groups: group 1, 7 patients in clinical class 2; group 2, 9 patients in clinical classes 3 and 4; and group 3, 7 patients in clinical classes 5 and 6. Moreover, 6 patients who underwent arterial bypass grafting procedures represented the control group. The tissues were suspended in organ baths that contained Krebs solution, and their mechanical responses were measured isometrically. The cumulative concentration-response curves to Ang II, NE, and ET-1 were performed at 90-minute intervals in each tissue. RESULTS: In the control tissues, NE, Ang II, and ET-1 induced concentration-dependent contractions with apparent affinities (pEC50, the negative logarithm to base 10 of the molar concentration of the agonist, which produces the 50% of the maximal effect) and maximal effects (maximum effect, g of contraction) that were equal to 7.06 +/- 0.23, 8.53 +/- 0.34, 7.63 +/- 0.10, and 2.21 +/- 0.33, 1.65 +/- 0.31, 2.60 +/- 0.77, respectively. Two main findings were evident in comparison of varicose veins with control tissues. First, the maximum effect that was evoked by all of the stimulants was reduced progressively with the increasing severity of the disease, which raised the third group to statistical significance for both NE and Ang II (P <.05). Second, a marked reduction of Ang II apparent affinity was already evident in tissues that were taken from patients in an early stage of the disease (P <.05). CONCLUSION: The demonstration of a significant reduction in Ang II and NE contractile activities and the important reduction of that of ET-1 in the diseased veins as compared with the control tissues extends the previous observations regarding the impairment of smooth muscle contractility in primary chronic venous insufficiency. Moreover, the dramatic reduction of Ang II affinity, which appears in an early stage of the disease, supports the hypothesis that such abnormality within the venous wall could play a role in the pathogenesis of primary varicose vein disease.

Symptomatic abdominal aortic aneurysm and "situs viscerum inversus." Diagnostic and therapeutic approach.

BACKGROUND: We report one case of symptomatic aneurysm of infrarenal abdominal aorta in a patient symptomatic for acute abdomen. METHODS: The patient was accepted at the Emergency Care Unit and the routine admission tests were taken. US of the abdomen revealed a <> (SVI) disposition of the organs and an aneurysm of the abdominal aorta below the renal arteries. Patient underwent an aorto-aortic straight graft CONCLUSIONS: In this case-report we show SVI cannot be considered a problem in the surgical treatment of symptomatic abdominal aortic aneurysms.

The heterozygous 20210 G/A prothrombin genotype is associated with early venous thrombosis in inherited thrombophilias and is not increased in frequency in artery disease.

A genetic variation in the 3'-untranslated region of the prothrombin mRNA (20210 G/A) has recently been reported to be associated with elevated plasma prothrombin levels and with an increased incidence of venous thrombosis. We determined the frequency of this mutation, the detection of which was improved by allele-specific amplification of exon 14 and by denaturing gradients (denaturing gradient gel electrophoresis), in cohorts of patients affected by venous thrombosis (n = 132) or by coronary or cerebrovascular diseases (n = 195) and in normal subjects from various populations. An overlapping frequency of the heterozygous genotype (4%) was found in normal subjects from Italy and Cyprus, and no carrier was detected in 40 subjects of Indian or Somali origin. The 20210 GA heterozygous genotype was not increased in frequency in patients with arterial disease. In contrast, the GA genotype was associated (P = .007) with venous thrombosis both in simple heterozygotes (16%) with a family history of thrombosis as well as in double heterozygotes (14%) for other known thrombophilic defects. A synergic interaction between the prothrombin 20210 GA genotype and the factor V Leiden mutation, both potentially affecting the prothrombinase complex, was suggested by the early onset of thrombosis (median age 22 years) in doubly heterozygous patients. The association of the 20210 A allele with higher prothrombin levels was confirmed in the Italian population. However, the prothrombin assay does not allow an efficient preselection of patients for the DNA analysis.

Seasonal variations in the rupture of abdominal aortic aneurysms.

From 1982 to 1994, 54 patients (47 men; mean age 72 years) were referred to the Hospital of Ferrara, Italy for spontaneous rupture of abdominal aortic aneurysm. Sixteen died in the emergency department and 38 underwent urgent surgery. Day and month of onset of acute symptoms leading to urgent surgery were recorded. A seasonal variation with significant peaks in spring and autumn was found. These findings are likely influenced by local environmental, social and epidemiological factors, but may be relevant for the appropriate timing of the follow-up and therapeutic strategies for abdominal aortic aneurysms.

[Morphologic anomalies of the extracranial internal carotid artery. Our experience]. / Anomalie morfologiche dell'arteria carotide interna extracranica. Nostra esperienza.

Cerebro-vascular insufficiency may be caused by morphologic anomalies of the extracranial internal carotid artery (10-15% of symptomatic patients). These alterations are characterized by anomalous elongation which conditions particular attitudes of the carotid: tortuosity, coiling, kinking. In the first case the artery assumes an "S" or "C" shape; in the second the elongation is more emphasized and the artery develops one or more loops; kinking, the most frequent morphologic anomaly, is a sharp angulation of the first part of the internal carotid artery. The etiology of these anomalies seems to be related to congenital causes, that may be unmasked by arterial growing old process. Surgical correction, indicated for symptomatic patients or patients with important hemodynamic alteration, requires rectilinearisation of the internal carotid artery associated with TEA eversion of the same.

[Aneurysms of the popliteal artery. Our experience apropos of 37 cases]. / Gli aneurismi dell'arteria poplitea. Nostra esperienza a proposito di 37 casi.

The authors describe their experience concerning the surgical treatment of aneurysmatic pathology of the popliteal artery. This is the most frequent site for aneurysm after aortic aneurysm. Since 1979 to 1994, 26 patients, 21 men and 5 women (mean age 65.8 years), have been treated at the Institute of Clinical Surgery of the University of Ferrara for a total of 37 popliteal aneurysms. Thirteen patients had more than one aneurysm. Before the operation, all patients underwent DSA, and echo Doppler, 7 with CAT and 4 with RMN. Twenty-nine substitutions, 7 by passes and 1 ligation were performed. Twelve of the 29 substitutions were made by reversed saphenous vein. Fourteen by PTFEe, and 3 by dacron. In 4 cases it was necessary to reimplant either the anterior tibial artery (3 cases) or the posterior tibial artery (1 case) separately. The results obtained were good especially in the post-trauma patients. Only 3 amputations were necessary due to graft obstruction immediately after surgery, and in post-traumatic conditions.

Experimental study on protein transmission through the human muscle fascia: preliminary results and application theory in lymphedema.

The presence of proteins (albumin and globulins) in lymphedematous tissue not only gives rise to colloidosmotic pressure but also produces an electrostatic charge endowing the proteins with individual features and different migration rates. The working hypothesis of the experimental study is to transfer lymph proteins from the upper fascia accumulation area to a subfascial drainage area by subjecting them to an adequate difference in potential. A double chamber, variable volume system with separation wall able to contain a 1 cm square of muscle fascia, was designed and built; the aim of the apparatus was to reproduce the subcutaneus zone separated by the fascia interposition, from the muscle-vascular zone. At the system was applied a variable electric field in six different experiments: 4 using porous synthetic membranes and 2 using human muscle fascia.