Circulating levels of cytokines (IL-6 and IL-1beta) in patients with intermittent claudication, at rest, after maximal exercise treadmill test and during restore phase. Could they be progression markers of the disease?

AIM: Inflammation is considered to be one of the main mechanisms for the development and progression of peripheral arterial disease (PAD). Many studies have demonstrated that maximal exercise enhances the acute inflammatory response in claudicant patients, but no one has assessed the duration of this acute inflammatory activation. The aim of this study was to assess of the inflammatory pattern in claudicants and of the inflammatory response after maximal exercise and during the recovery from calf pain. METHODS: Eleven patients with moderate claudication (MC) (age: 60.5+/-5.8 years; body mass index [BMI]: 27.5+/-4.6; absolute claudication distance [ACD]: 165.4+/-38), 10 patients with severe claudication (SC) (age: 60.3+/-5 years; BMI: 27+/-4.5; ACD: 91+/-11.3) and 8 healthy subjects (age: 59.4+/-6.8; BMI: 28.7+/-4.16) underwent to maximal treadmill test (speed 2.5 km/h, slope 15%). At rest, just after stop of the exercise (appearance of calf pain in patients, and 6 min of treadmill in controls) the circulating levels of interleukin (IL)-1beta and IL-6 have been measured. STATISTICAL ANALYSIS: variance of mean values, Bonferroni t-test, split plot variance model, variance of d stop-before and stop-recovery have been utilized. P<0.05 has been considered the significant cut-off of the differences. RESULTS: The maximal exercise excited significant (P<0.01) inflammatory activation in all patients: MC (rest IL-1beta: 1.55, 3.3 at stop; rest IL-6: 5.97, 8.38 at the stop); SC (rest IL-1beta: 2.97, 5.72 at stop; rest IL-6: 6.98, 9.99 at the stop). During recovery, MC showed a reduction of the inflammatory activation, whilst SC showed further increase (IL-1beta: 7.55; IL-6: 11.94). CONCLUSION: The study confirms the higher inflammatory activation in claudicants and its enhancement after maximal exercise. During recovery, we found two kinds of response: type 1 (controls and MC), in which inflammation subsides, and type 2 (SC) characterized by further inflammatory increase. This trend is not univocal: 3 MC showed a type 2 response and 2 SC showed a type 1. In conclusion, inflammatory activation may depend not only on the degree of endothelial damage, but also on the individual inflammatory attitude, better assessed after maximal exercise than baseline values. This individual inflammatory responsiveness, considering the role of the rest measurement of markers of inflammation recently discussed, could be a useful marker for aggressive PAD.

[Primary antiphospholipid syndrome and hyperhomocysteinemia: a study of a group of 29 patients]. / Sindrome da anticorpi antifosfolipidi primaria e iperomocisteinemia: studio di un gruppo di 29 pazienti.

OBJECTIVE: In order to investigate the potential role of hyperhomocysteinemia as an additional risk factor for thrombotic events, we studied its prevalence in patients with primary antiphospholipid syndrome (APS) and evaluated its association with different clinical features. METHODS: We enrolled 29 patients without any current evidence of underlying connective tissue disorder and fulfilling the Sapporo preliminary classification criteria for APS. RESULTS: Ten (34,4%) patients showed mild hyperhomocysteinemia (18,34 micromol/L +/- 2,04 DS). Nine had history of cerebrovascular disease, isolated (3 cases) or more often (6 cases) in association with other APS features. All patients, but one, showed multiple ischemic cerebral lesions. Seven of the 10 patients with hyperhomocysteinemia had multiple antiphospholipid antibody positivity and presented more frequently (6 cases) multi-site vascular involvement. CONCLUSIONS: The frequency of hyperhomocysteinemia in patients with primary APS is not negligible and appears to be associated with cerebral microangiopathic disease, multiple antiphospholipid antibody positivity and the simultaneous involvement of different vascular districts. For this reason and because hyperhomocysteinemia can be easily corrected with safe and relatively inexpensive therapeutic interventions, we advocate the measurement of homocysteinemia in every patient affected by APS and possibly in subjects with positive antiphospholipid antibody without a history of thrombosis.

Spontaneous recanalization of internal carotid artery occlusion evaluated with color flow imaging and contrast arteriography.

AIM: In strokes of embolic origin a partial recanalization of the intracranial occluded vessel occurs with a high incidence (as high as 80%). In the literature, we find few cases of revascularization, detected with color flow imaging (CFI) or with arteriography (AGF), at carotid siphon or at the origin of an occluded internal carotid artery (ICA). Up to now there have been no reliable data on the incidence and clinical consequences of SR of an extracranial ICA occlusion. In this case-report we document 8 cases of SR of occluded ICA observed in the last 10 years in our Care Unit. METHODS: We observed 8 complete ICA occlusion at the origin, detected with CFI (8 of 8) and with AGF (7 of 8). All symptomatic patients and 2 of 5 asymptomatic patients underwent CT scan in the acute phase of stroke. All patients underwent CFI follow-up (every 6-12 monhts) to evaluate contralateral CCA and ICA and the presence of new focal neurological symptoms. All patients assumed BMT (antiplatelet or anticoagulant therapy). RESULTS: SR occurred in 6 patients between 24 and 96 months, in 1 patient within 8 months and 1 patient within 6 months from the diagnosis of ICA occlusion. Diagnosis of SR was based in all patients with CFI and in 4 patients confirmed with AGF. Five patients underwent CT scan that excluded haemorrhagic transformation of previous ischemic areas or new ischemic events (2 patients did CT scan only after SR). All patients underwent CFI follow-up in a 3-88 months period. There were no new focal neurological symptoms in 7 of 8 patients, 1 patient presented aspecific neurological symptoms. CONCLUSION: Diagnosing SR of occluded extracranical ICA seems to be more frequent than expected. SR is an event that has to be researched in follow-up of these patients; besides, it seems to have a relatively benign outcome with respect to the onset of new neurological symptoms.

Clinical outcome of patients with internal carotid artery occlusion: a prospective follow-up study.

PURPOSE: We prospectively evaluated whether, and to what extent, different clinical presentations (symptomatic or asymptomatic) or the presence of atherosclerotic narrowing of the contralateral carotid system modifies the mortality rate and the incidence of nonfatal cerebrovascular events in patients with internal carotid artery (ICA) occlusion. METHODS: A prospective cohort study was conducted in the Unit Care of Angiology at the University Hospital of Padua in Italy. Consecutive patients with ICA occlusion were eligible for the study. Between 1990 and 1991, 41 such patients were identified at our center. All patients were observed prospectively for a mean of 44.5 months, except for one patient who was lost to follow-up after 12 months. Patients with severe (ie, more than 75%) stenosis of the contralateral internal carotid artery were scheduled for thromboendarterectomy. ICA occlusion was objectively documented in all patients by using a combination of echo-color Doppler scanning and continuous-wave Doppler scanning (periorbital flow). RESULTS: The overall mortality rate was 22.0% (95% CI, 10.6-37.6), and the stroke-related mortality rate was 7.3% (95% CI, 1.5-19.9). No differences in overall and stroke-related mortality rates were observed between asymptomatic and symptomatic patients. None of the patients experienced nonfatal cerebrovascular events. CONCLUSION: ICA occlusion seems to represent a relatively benign condition, in both its symptomatic and asymptomatic presentation. The presence of an atherosclerotic stenosis less than 75% of the contralateral ICA does not seem to worsen the prognosis of this condition.

An unexpectedly high rate of pulmonary embolism in patients with superficial thrombophlebitis of the thigh.

PURPOSE: The rate of objectively proven pulmonary embolism in patients with thrombophlebitis of the greater saphenous vein was studied. METHODS: Consecutive ambulant patients with thrombophlebitis of the greater saphenous vein, involving the above-knee segment, underwent a complete venous echo color Doppler examination of the lower limbs, perfusion lung scanning, and chest radiography. A high probability of pulmonary embolism was defined as the presence of two or more large segmental defects, one large and two or more moderate perfusion defects, or four or more moderate perfusion defects, with no corresponding abnormality found by means of chest radiography. RESULTS: Of the 21 patients included in the study, findings compatible with a high probability of pulmonary embolism were detected in seven patients (33.3%; 95% CI, 14.6 to 57. 0), although clinical symptoms of pulmonary embolism were present only in one patient. No association was found between the presence of thrombosis at the saphenofemoral junction and the risk for pulmonary embolism. CONCLUSION: The rate of pulmonary embolism in patients with thrombophlebitis of the greater saphenous vein is unexpectedly high. This risk is similarly high in patients with thrombosis at the saphenofemoral junction and in patients without thrombosis at the saphenofemoral junction. Our results are consistent with those of other recent investigations and suggest that superficial thrombophlebitis of the thigh is not as benign a disease entity as previously described.

Incidence of risk of thromboembolism during treatment high-grade gliomas: a prospective study.

A prospective study of a series of 77 patients on adjuvant radiochemotherapy following surgery for high-grade gliomas was conducted to evaluate the risk of deep vein thrombosis and identify risk factors. We found a 20.8% risk of deep vein thrombosis at 12 months (standard error = 4.8%) and a 31.7% risk (standard error = 7.4%) at 24 months (Kaplan-Meier method). Twenty patients (26%) developed deep vein thrombosis with a maximum incidence within the first 7 months after surgery when chemotherapy was still being administered, often with corticosteroids. The risk factors identified were histology (glioblastoma versus anaplastic astrocytoma, P = 0.032, log rank test; 0.0485 L-ratio) and the presence of paresis (P = 0.010, log rank test; 0.0161 L-ratio). A borderline tendency was found for an association between the deep vein thrombosis site and the side of paresis (P = 0.103, Fisher's exact test). Four patients (5%) had massive pulmonary embolism, which was fatal in 3 (4%).

Diagnosis of high-grade stenosis of innominate artery.

Although pathology of the innominate artery (IA) is not frequent, it causes relevant impairment of extracranial circulation and sometimes cerebrovascular events. Definite differentiation of high-grade stenosis from occlusion of the IA has not been obtained until now with continuous-wave (C.W.) Doppler and duplex system ultrasound, and thus the direct evaluation of IA is not reliable by noninvasive methods. In this study the authors suggest an indirect method of evaluation of IA pathology based on the study of carotid, subclavian, and vertebral arteries (VA) with echo-Doppler-color-flow (EDCF) (with linear--phase array probes of 7.5 and 5 MHz). In the last two years they studied 6 patients with IA pathology (2 with occlusion (occ), 1 with stenosis of 80% and 3 with subocclusive stenosis > 90%). In both patients with occ, right VA flow was inverted, and also the right common carotid (CC) was involved (occ in 1 case and inverted flow in the other); in the 3 subocclusive stenoses a lowered systolic flow in the CC was recorded (48 vs 85 cm/sec, 41 vs 77, and 23 vs 109). In the 80% stenosis, besides the inverted flow in VA, only a reduced diastolic flow in CC was also recorded (19 vs 33 cm/sec measured in the left side). All patients with high grade stenosis were successfully confirmed by an angiographic study, including the different degree of stenosis. Five of the 6 patients underwent surgical correction with a restored flow in the previously involved artery. Only 1 patient with occlusion is waiting for surgical correction.(ABSTRACT TRUNCATED AT 250 WORDS)

Takayasu's arteritis: anatomic change before and after steroid therapy evaluated by angiography and echo-Doppler color-flow.

A 36-year-old Italian woman with active Takayasu's disease presented a bilateral occlusions of subclavian artery and stenosis of bilateral common carotid arteries: the maximal diameter stenosis, measured with echo-Doppler color-flow (EDCF) in the longitudinal section was of 43.5 +/- 2.4% on the right and 61 +/- 1.4% on the left. Prednisolone was administered for 30 months at doses from 25 to 6 mg daily (12.5 mg every two days). During steroid therapy we could monitor by EDCF the anatomic change of the involved vessel and a final decrease in carotid wall thickening of 19.8% on the left and 14.0% on the right side. This work demonstrates for the first time that duplex sonography may be an useful tool to asses possible anatomic changes in the carotid lesions of Takayasu's arteritis in response to steroid therapy.

Peripheral arterial occlusion in infants--a report of two cases treated conservatively.

The occlusion of major arteries in newborns is usually associated with catheterization of the umbilical vessels. It occurs very rarely instead as a primary disorder, and the cause is still unclear. We present two new cases of newborns with this type of disease, which were resolved with the only medical treatment. The literature is reviewed, and the usefulness of the different diagnostic procedures is discussed.

Hereditary heparin cofactor II deficiency and thrombosis: report of six patients belonging to two separate kindreds.

We describe six patients belonging to two families with congenital heparin cofactor II deficiency (HC II). The affected members had low levels of HC II antigen and activity, and no abnormalities in HC II electrophoretic mobility were detected in the presence of heparin or dermatan sulphate during the first migration of crossed immunoelectrophoresis. These data suggested that patients had a type I (true) HC II deficiency. The association of thrombotic manifestations with congenital HC II deficiency has not been completely clarified. In these two families, thrombotic events occurred in two out of six affected members. In addition, there was a high incidence of spontaneous abortion in the affected females. Finally, the association of congenital HC II deficiency with angiomatosis was also observed in one patient.

Efficacy of indobufen in the treatment of intermittent claudication.

The aim of this trial was to assess the activity of indobufen compared with placebo in peripheral occlusive arterial disease of the lower limbs of atherosclerotic or diabetic origin. Fifty-two outpatients were admitted to the randomized, double-blind study and were given either an indobufen 200-mg tablet (28 subjects) or placebo (24) for six months. Painfree walking distance on a treadmill at a constant speed (4 km/h) and slope (10 degrees) was assessed before and after three and six months' treatment. The painfree walking distance before treatment with indobufen or placebo averaged 153 +/- 23.02 (mean +/- SE) and 199 +/- 30.58 (mean +/- SE) meters respectively. After six months' treatment with active drug or placebo, this parameter reached 610 +/- 115.36 (p less than 0.01) and 243 +/- 32.49 (p greater than 0.05) meters respectively. The difference between the two treatments was statistically significant in favor of indobufen (p less than 0.01 Dunn's test).