PTA of venous strictures in patients with CCSVI is safe, and especially in patients with RR, the clinical course positively influenced clinical and QOL parameters of the associated MS compared with the preoperative assessment. Restenosis rates are elevated in the IJVs but very promising in the AZY, suggesting the need to improve endovascular techniques in the former. The results of this pilot study warrant a subsequent randomized control study.
Background Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence.Methods ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362.
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.
The dynamic NIRS-based test, quantifying muscle metabolic response according to presence and degree of PAD, allows the evaluation of patients with walking disabilities.
xercise training is an effective, low-cost therapy that improves the functional ability of patients with intermittent claudication. [1][2][3][4] Its diffusion could be favoured by models of intervention that would help ensure functional and cardiovascular improvements, patient compliance and lower costs for the healthcare system.In order to optimise these positive outcomes, the model of intervention and the prescribed exercise intensity are of primary importance. Unfortunately, specific recommendations regarding exercise prescription and programming are limited. 2 However, it is known that exercise is preferably carried out at moderate to near-maximal pain, and that better results are obtained at the hospital under the supervision of the rehabilitative team. These center-based programs for peripheral arterial disease (PAD) have been found to be more effective at improving walking ability in training up to 6 months compared with home-based programs, with unclear effect of supervision. 5,6 On the other hand, home-based programs, which are based on simple instructions about the exercise to be performed (eg, walk up to pain tolerance), in general, show higher long-term adherence to exercise, with lower cost to the healthcare system. 6 An alternative model without supervision, based on the assessment of functional capacity at hospital during monthly check-ups and a personalized prescription of exercise to be performed at home at maximal asymptomatic speed (MAS) has been developed recently. 7,8 This novel approach to rehabilitation for patients with PAD, the 'test in -train out' program (Ti-To), aims to combine the advantages of a traditional home-based program (eg, long-term adherence and lower cost) with those of a supervised program (especially, exercise at selected intensities).The Ti-To program makes use of the MAS; that is, the walking intensity below the individual pain threshold speed (PTS) 9 that combines pain-free training with functional, hemodynamic and cardiovascular adaptations. 7 The present study aimed to test the effectiveness of the Ti-To program on walking ability and hemodynamic parameters in a group of patients exercising at home at their MAS compared with patients following a traditional home-based free walking exercise (Tr-E) at self-selected speeds up to pain tolerance over a 6-month period. Background Exercise training reduces walking disability in peripheral arterial disease (PAD). This non-randomized study evaluates the effects on walking ability and hemodynamic parameters of a novel approach to home-based rehabilitation, the test in -train out program (Ti-To), compared with the traditional home-based free walking exercise (Tr-E). Methods and Results A total of 143 patients with claudication (117 men, average age 68±10 years), were included in a Ti-To (n=83) or Tr-E program (n=60). Evaluations, which were carried out upon entry and at 1, 2, 3, 4 and 6 months, included: self-reported claudication, walking ability (ie, absolute claudication distance, pain threshold speed), resting/exercise hea...
Selected near-infrared spectroscopy (NIRS) parameters were assessed in healthy untrained participants and in peripheral arterial disease (PAD) trained patients to evaluate their usefulness in rehabilitative outcome. Forty-five PAD and 15 healthy participants were studied at entry and at 34 ± 2 weeks. Healthy participants performed their usual activities. Patients with PAD performed 2 home-based programs: structured at prescribed pace (S-pre, n = 31) and unstructured at free pace (U-free, n = 14). We measured ankle-brachial index (ABI), NIRS calf oxygen consumption at rest, NIRS dynamic muscle perfusion during an incremental test, and walking capacity. In all patients with PAD the NIRS parameters significantly increased approaching the stable values of untrained healthy participants. Among PAD, only S-pre group showed significant improvements in hemodynamic, functional, and NIRS parameters with selective adaptations in the worse legs. The assessment of NIRS parameters, that were found stable without training in healthy and modified in PAD only following structured training, might outline the local exercise-induced adaptations.
Urotensin II is a cyclic undecapeptide which activates the GPR14 receptor and exerts potent vasoconstrictor effects in some species of fish and mammals. The present study intended to investigate isolated vessels from various species in an attempt to find sensitive preparations to be used in studies of the human urotensin (hU-II)/GPR14 system. Contractile responses evoked by noradrenaline (NA), angiotensin II (Ang II), endothelin 1 (ET-1) and hU-II were measured in large vessels (aorta and some large arteries and veins) of rats, guinea pigs, rabbits, pigs and humans. Relaxing effects of hU-II, bradykinin (BK) and substance P (SP) were measured in pig coronary arteries contracted with KCl 30 mM. The rat mesenteric vasculature was investigated from the arterial and venous site to establish the function of ET-1 and hU-II receptors. Results indicate that the only preparation showing high sensitivity to hU-II (pEC(50)=8.27) is the rat aorta, whose contractions in response to hU-II develop slowly and persist for hours, similar to those of ET-1 (pEC(50)=8.35). Effects of NA (pEC(50)=8.12) and Ang II (pEC(50)=7.95) develop and reverse more rapidly. Tissues treated with ET-1 and hU-II show marked desensitization, in contrast to those treated with NA. Specific antagonists for alpha(1) (prazosin, p A(2)=10.46), AT(1) (EXP 3174, p A(2)=10.20), 5HT(2) (ketanserine, p A(2)=8.61) and ET(A)-ET(B) (bosentan, p A(2)=6.88) receptors were shown to block the effects of the respective agonists, while being inactive against hU-II. In some vessels, hU-II behaved as an highly potent but scarcely effective contractile agent. It is concluded that: the hU-II/GPR14 is not a functional contractile system in vessels of several species, in contrast with NA/alpha(1), Ang II/AT(1), 5HT/5HT(2) and ET-1/ET(A)-ET(B). The rat aorta appears however to be a sensitive and reliable preparation for evaluating biological activities of hU-II and related peptides.
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