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Biomedical subjects

Ulrika Palmer-Kazen

Publications and source records attributed to Ulrika Palmer-Kazen.

3 recordsLinked to original sources

Vascular endothelial cell growth factor and fibroblast growth factor 2 expression in patients with critical limb ischemia.

BACKGROUND: For patients with critical limb ischemia (CLI), there is a great need for alternative treatment strategies. One option is therapeutic angiogenesis by administration of vascular growth factors. The lack of convincing clinical data supporting this strategy may be due to the ignorance of endogenous angiogenic processes in CLI. To evaluate the importance of vascular growth factors in the pathogenesis in CLI and provide information for clinical growth factor treatment trials, we determined the levels of vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) in the ischemic legs of patients with this disease. METHODS: Skin and muscle biopsies from the calf and groin were gathered from 25 patients with CLI. Control samples came from 10 orthopedic patients and from 5 patients who were undergoing coronary artery bypass. The concentration of VEGF and FGF-2 in the biopsies was measured by enzyme-linked immunoassay, and to localize growth factor production, biopsied sections were immunostained. RESULTS: Patients with CLI had lower levels of VEGF in distal skin samples than in proximal ones (mean difference: 16.7 pg/mg total protein, 95% confidence interval: -1.0 to -32.3, P =.038), but these levels were similar to those in distal samples from control subjects (8.0, -4.6 to 20.5, P =.65). In muscle, VEGF concentrations were similar in calf and groin (5.4, -12.4 to 23.1, P =.55), but distal levels were higher than in distal samples from control subjects (23.7, 1.2 to 56.7, P =.028). Skin FGF levels tended to be higher in distal samples (45.3, 26.5 to 117.5, P =.090) and were higher than in skin from control subjects (106.2, -11.4 to 223.8, P =.050). Also in muscle, distal samples had higher levels of FGF-2 (35.6, -1.6 to 59.7, P =.006), but these levels were similar to what was found in control subjects (29.4., -16.3 to 81.2, P =.39). Growth factors were located in connective tissue between muscle fibers. In skin, the predominant FGF-2 staining was just below the epidermal layer, whereas VEGF appeared in the dermal layer. CONCLUSIONS: The results indicate that there are elevated concentrations of FGF-2 in calf muscle, whereas VEGF concentrations do not appear to be higher in the ischemic part of the leg in patients with CLI. These findings suggest that VEGF supplementation may be a more appropriate strategy for therapeutic angiogenesis to the calf area for CLI than FGF-2.

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Arteriogenesis in peripheral arterial disease.

Lower extremity peripheral arterial disease (PAD) most frequently presents with lower limb pain on walking--intermittent claudication. As the disease progresses the patient might suffer from rest pain and/or ischemic ulceration--critical limb ischemia (CLI). The management of patients with PAD consists of life-style modifications and pharmacotherapy addressing the risk factors to minimize the risk for disease progression and mortality in myocardial infarction and stroke. Symptomatic invasive treatment consists of surgical or endovascular revascularization. Unfortunately, about 20-30% of patients with CLI can not be treated by any of these methods and the only option for them is often amputation. For this group of patients there is a great need for alternative treatment strategies and several strategies are currently tested to stimulate collateral artery growth (arteriogenesis). Arteriogenesis is defined as growth of preexisting arteriolar connections into true collateral arteries. It relies on a complex combination of increased shear stress, different growth factors, cytokines, proteolytic enzymes and initial local inflammation. It is probable that this process is important for disease progression and the pathophysiology of leg ischemia, but its impact needs to be further elucidated. Such efforts will also benefit attempts to stimulate arteriogenesis as therapy for leg ischemia. This article briefly discusses the basic mechanisms underlying arteriogenesis, and speculates how this knowledge influences our view of the pathophysiology and treatment of PAD, particularly lower limb ischemia.

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Risk factors for poor collateral development in claudication.

The objective of this retrospective, cross-sectional study was to determine risk factors for poor collateral development in patients with claudication. The authors listed all patients with calf claudication who had undergone angiography in this hospital between 1999 and 2001 and extracted those with superficial femoral artery (SFA) occlusion, a popliteal artery without major lesions, and at least 1 patent calf artery. Forty-five patients met the criteria, and concomitant disease and claudication characteristics, ankle/brachial index (ABI) and number of outflow vessels were recorded. Three blinded observers calculated the number of collaterals on the angiograms, and the collateral count was related to the other factors by use of regression analysis. The mean patient age was 69 years (SD 11), and 62% were women. Their walking distance was 90 m (77) and ABI 0.47 (0.15). Thirty-three percent had diabetes and 50% had duration of symptoms longer than 5 years. The mean number of collaterals bypassing the occlusion was 15.1 (SD 4.8). Univariate regression analysis indicated an association (p <0.08) between few collateral vessels and diabetes, short duration of symptoms, current smoking habits, and old age. In the multivariate analysis only diabetes and short duration of symptoms were related to having few collaterals. In patients with claudication and SFA occlusion, few collaterals from the deep femoral artery appear to be associated with having diabetes and a short duration of symptoms.

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