Basic fibroblast growth factor in patients with intermittent claudication: results of a phase I trial.
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OBJECTIVES: This phase I study was designed to evaluate the safety, tolerability and pharmacokinetics of intra-arterial basic fibroblast growth factor (bFGF) in patients with atherosclerotic peripheral arterial disease (PVD) and intermittent claudication. We also assessed the effects of basic fibroblast growth factor (bFGF) on calf blood flow as a measure of biologic activity. BACKGROUND: Preclinical studies have shown that bFGF, an angiogenic peptide, promotes collateral development in animal models of myocardial and hind limb ischemia. The safety and efficacy of bFGF in patients is unknown, and early clinical trials are underway in coronary and peripheral arterial disease. METHODS: A double-blind, placebo-controlled, dose-escalation trial was conducted in patients with claudication demonstrating ankle/brachial index <0.8. Patients were randomly assigned to placebo (n = 6), 10 microg/kg of bFGF (n = 4), 30 microg/kg of bFGF once (n = 5) and 30 microg/kg of bFGF on two consecutive days (n = 4). Study drug was infused into the femoral artery of the ischemic leg. Detailed safety information including retinal photography for neovascularization were obtained through one year. Calf blood flow was measured with strain gauge plethysmography in the two higher dose treatment groups and in four placebo patients at baseline, one month and three to seven months after treatment. RESULTS: Intra-arterial bFGF was safe and well-tolerated. The half-life was 46 +/- 21 min. Calf blood flow increased at one month by 66 +/- 26% (mean +/- SEM) and at six months by 153 +/- 51% in bFGF-treated patients (n = 9, p = 0.002). Flow did not change significantly in the placebo group. CONCLUSIONS: In this initial randomized, double-blind, placebo-controlled trial in patients with atherosclerotic PVD and claudication, bFGF was well-tolerated. The data suggest a salutary biologic effect, and initiation of phase 2 trials is warranted. (+info)
Assessment of generic health-related quality of life in patients with intermittent claudication.
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OBJECTIVES: to measure quality of life in patients with intermittent claudication and evaluate the ability of patients and vascular surgeons to make a similar assessment. DESIGN, MATERIALS AND METHODS: in this prospective study patients with intermittent claudication attending two vascular clinics were asked to complete a generic health-related quality of life instrument (MOS SF-36). Patient quality of life and vascular surgeons' assessment of patient quality of life were further evaluated using a single question/adjectival scale response combination. RESULTS: patients' self-assessment of their quality of life correlated better with the SF-36 score than did the surgeons' assessment. There was little correlation between the surgeons' and patients' own assessment of quality of life. The surgeons differed significantly from each other in their assessments. Claudicants had lower SF-36 scores than population norms in pain and physical aspects of quality of life. CONCLUSIONS: claudicants have worse quality of life than the general population, with pain and physical limitations being the most important domains. Surgeons predict the quality of life of claudicating patients less accurately than patients do themselves, and may differ from their colleagues in such assessments. Objective quality of life assessment in claudicants should be undertaken before treatment is decided. (+info)
Endovascular repair of aortic allograft aneurysmal degeneration: a case report.
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Aortoenteric graft fistula remains a dreadful complication of aortic surgery. Good results have been reported using in situ graft replacement with arterial allografts. Late aneurysmal degeneration of the graft itself may necessitate further repair. We report the case of such an aneurysmal degeneration 7 years after implantation of the allograft. Endovascular repair was performed with a Vanguard device; complete exclusion was obtained immediately. At 6-month follow-up, the patient was alive and well. Duplex and computed tomography scans showed an excluded aneurysm with a slight reduction in size. Endovascular stent grafting may be a therapeutic option for treating patients with late allograft degeneration. (+info)
Alcohol consumption and risk of intermittent claudication in the Framingham Heart Study.
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BACKGROUND: Intermittent claudication (IC) is associated with an increased risk of cardiovascular disease morbidity and mortality. The relation of alcohol consumption to the risk of IC remains controversial. The purpose of this study was to assess the relation of alcohol consumption and type of beverage to the development of IC among participants in the Framingham Heart Study. METHODS AND RESULTS: Alcohol consumption was categorized as 0, 1 to 6, 7 to 12, 13 to 24, and >/=25 g/d. During a mean follow-up of 6.8 years, 414 subjects developed IC. From the lowest to the highest category of alcohol intake, the age-standardized incidence rates of IC were 5.3, 4.1, 4.2, 3.2, and 4.6 cases/1000 person-years for men and 3.4, 2.5, 1.5, 1.9, and 2.5, respectively, for women. A multivariate Cox regression model demonstrated an inverse relation, with the lowest IC risk at levels of 13 to 24 g/d for men and 7 to 12 g/d for women compared with nondrinkers; the hazard ratio (95% CI) was 0.67 (0.42 to 0.99) for men and 0.44 (0.23 to 0.80) for women. This protective effect was seen mostly with wine and beer consumption. CONCLUSIONS: Our data are consistent with a protective effect of moderate alcohol consumption on IC risk, with lowest risk observed in men consuming 13 to 24 g/d (1 to 2 drinks/d) and in women consuming 7 to 12 g/d (0.5 to 1 drink/d). (+info)
Outcome events in patients with claudication: a 15-year study in 2777 patients.
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OBJECTIVE: The purpose of this study was to delineate the natural history of claudication and determine risk factors for death. METHODS: We reviewed the key outcomes (death, revascularization, amputation) in 2777 male patients with claudication identified over 15 years at a Veterans Administration hospital with both clinical and noninvasive criteria. Patients with rest pain or ulcers were excluded. Data were analyzed with life-table and Cox hazard models. RESULTS: The mean follow-up was 47 months. The cohort exhibited a mortality rate of 12% per year, which was significantly (P <.05) more than the age-adjusted US male population. Among the deaths in which the cause was known, 66% were due to heart disease. We examined several baseline risk factors in a multivariate Cox model. Four were significant (P <.01) independent predictors of death: older age (relative risk [RR] = 1.3 per decade), lower ankle-brachial index (RR = 1.2 for 0.2 change), diabetes requiring medication (RR = 1.4), and stroke (RR = 1.4). The model can be used to estimate the mortality rate for specific patients. Surprisingly, a history of angina and myocardial infarction was not a significant predictor. Major and minor amputations had a 10-year cumulative rate less than 10%. Revascularization procedures occurred with a 10-year cumulative rate of 18%. CONCLUSIONS: We found a high mortality rate in this large cohort and four independent risk factors that have a large impact on survival. Risk stratification with our model may be useful in determining an overall therapeutic plan for claudicants. A history of angina and myocardial infarction was not a useful predictor of death, suggesting that many patients in our cohort presented with claudication before having coronary artery symptoms. Our data also indicate that claudicants have a low risk of major amputation at 10-year follow-up. (+info)
The inflammatory response to upper and lower limb exercise and the effects of exercise training in patients with claudication.
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PURPOSE: We have previously shown that a program of upper limb exercise training can induce significant improvements in walking distance in patients with claudication. This study assessed whether upper limb exercise avoids the systemic inflammatory responses associated with lower limb exercise and also whether the inflammatory response to acute lower limb exertion is modified by a program of supervised exercise training. METHODS: Fifty-two patients with stable intermittent claudication were randomized into two groups who underwent 6 weeks of supervised upper (n = 26) or lower (n = 26) limb cardiorespiratory exercise training. A parallel control group (n = 15) was provided with lifestyle advice only. Neutrophil activation markers (CD11b and CD66b) and plasma levels of von Willebrand factor (marker of endothelial damage) in response to an acute bout of sustained upper and lower limb exercise were assessed before and after the period of training. Plasma levels of soluble E-selectin (marker of endothelial activation) were also determined before and after the training period. RESULTS: An acute bout of sustained lower limb exercise significantly increased the intensity of CD11b and CD66b expression by peripheral blood neutrophils in all groups, whereas upper limb exercise had no effect. Resting neutrophil expression of CD11b and CD66b and circulating von Willebrand factor levels were unaffected by the training program, as were the inflammatory responses to an acute bout of sustained upper and lower limb muscular work, despite the fact that both training programs significantly increased walking distances. CONCLUSIONS: These findings indicate that upper limb exercise training programs may offer certain advantages over currently prescribed lower limb programs. Our results show that exercising nonischemic muscles in a way that promotes improved cardiorespiratory function and walking capacity can avoid the potentially deleterious systemic inflammatory responses associated with lower limb exertion in patients with stable intermittent claudication. (+info)
Causes of late mortality in patients with disabling intermittent claudication.
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The long-term prognosis of patients suffering from intermittent ischemic claudication is reportedly worse than that of the normal population. The outcome of patients with ischemic claudication admitted to hospital was reviewed retrospectively to identify the causes of late death. The cumulative survival rates for patients with claudication were 94.6% at 1 year, 79.4% at 3 years, 67.3% at 5 years and 37.4% at 10 years. The 3 major causes of death, that is, ischemic heart disease, malignancy, and cerebrovascular accident, were equally common. The younger patients tended to die of ischemic heart disease, whereas the older patients died of cerebrovascular accidents. Malignancies caused a similar number of late deaths in all age groups. These results suggest that specific care should be given to patients with intermittent claudication based on the age-related causes of death. (+info)
Quality of life in patients with intermittent claudication using the World Health Organisation (WHO) questionnaire.
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OBJECTIVE: to assess quality of life (QOL) in patients with intermittent claudication. DESIGN: a prospective, open study. MATERIAL AND METHOD: one hundred and fifty-one consecutive claudicants (100 men, 51 women), and 161 healthy controls (70 men and 91 women) completed an adapted version of the World Health Organisation Quality of Life Assessment Instrument-100. RESULTS: patients scored significantly worse on the domains Physical health and Level of independence, as well as on the facets Pain and discomfort, Energy and fatigue, Mobility, Activities of daily living, Dependence on medication and treatments, Working capacity, Negative feelings, Recreation and leisure and Overall QOL and general health. Increasing disease to incapacitating claudication affected only the facet Mobility and the domain Level of independence. CONCLUSION: QOL in patients with intermittent claudication is reduced in many aspects. Where co-morbidity seems to affect QOL strongly, the effect of walking distance on QOL might be small. These findings may justify a reserved attitude towards invasive, even minimally invasive treatment of these patients. (+info)