Skin capillary permeability in the diabetic foot with critical limb ischaemia: the effects of a phVEGF165 gene product.

AIMS: To measure capillary permeability, assessed by skin capillary sodium fluorescein (NaF) leakage, in patients with diabetes mellitus with critical limb ischaemia (DM-CLI) and to compare the effects of vascular endothelial growth factor (VEGF) with those of placebo. METHODS: NaF leakage was assessed in 17 patients with DM-CLI, in 24 diabetes mellitus (DM) patients without clinical signs of macrovascular disease or neuropathy (DM-C) and in 22 healthy control subjects. The 17 DM-CLI patients were randomized to receive phVEGF165 gene product (n = 11) or placebo (n = 6). Measurements were repeated after 28 days. RESULTS: DM-CLI patients had a longer dye arrival time (DAT), but NaF leakage was similar to control subjects, while capillary permeability was increased in DM-C compared with control subjects. Leakage curve rose in patients receiving VEGF and fell in those receiving placebo, 28 days after administration. The decrease in DAT in the VEGF group was not significant, whilst DAT rose in the placebo group. Perfusion pressures were similar in the two groups. CONCLUSION: No increase in capillary leakage in DM-CLI was found, probably because an increased capillary filtration coefficient is counterbalanced by a marked fall in perfusion pressures. Increased capillary leakage may be one explanation for oedema formation after VEGF treatment.

Treatment with intramuscular vascular endothelial growth factor gene compared with placebo for patients with diabetes mellitus and critical limb ischemia: a double-blind randomized trial.

Despite advances in revascularization techniques, limb salvage and relief of pain cannot be achieved in many diabetic patients with diffuse peripheral vascular disease. Our objective was to determine the effect of intramuscular administration of phVEGF165 (vascular endothelial growth factor gene-carrying plasmid) on critical limb ischemia (CLI) compared with placebo (0.9% NaCl). A double-blind, placebo-controlled study was performed in 54 adult diabetic patients with CLI. The primary end point was the amputation rate at 100 days. Secondary end points were a 15% increase in pressure indices (ankle-to-brachial index and toe-to-brachial index), clinical improvement (skin, pain, and Quality of Life score), and safety. In patients (n=27) treated with placebo versus phVEGF165-treated patients (n=27) the following results were found: 6 amputations versus 3 (p=not significant [NS]); hemodynamic improvement in 1 versus 7 (p=0.05); improvement in skin ulcers, 0 versus 7 (p=0.01); decrease in pain, 2 versus 5 (p=NS); and overall, 3 versus 14 responding patients (p=0.003). No grade 3 or 4 adverse effects were seen in these patients. We conclude that this small, randomized gene therapy study failed to meet the primary objective of significant amputation reduction. However, significant and meaningful improvement was found in patients treated with a VEGF165-containing plasmid. There were no substantial adverse events.

Therapeutic angiogenesis with vascular endothelial growth factor in peripheral and coronary artery disease: a review.

Therapeutic angiogenesis constitutes an alternative treatment for patients with extensive tissue ischaemia in whom primary vascular reconstruction procedures are not feasible or have previously failed. At present vascular endothelial growth factor (VEGF) has been the most widely used angiogenic factor in experimental and human clinical trials. Early clinical data provide evidence that gene transfer of the VEGF gene can achieve beneficial angiogenesis, with minimal side-effects. Ongoing phase III clinical studies will reveal definitive efficacy.

[2 patients with atypical manifestations of cat-scratch disease]. / Twee patiënten met atypische manifestaties van kattenkrabziekte.

In 2 boys aged 8 years and 10 months, respectively, uncommon manifestations of cat scratch disease were seen. The first patient had acute encephalopathy: coma and generalized tonic-clinic convulsions. The second patient was presented with fever and peripheral lymphadenopathy in combination with hypodense lesions in the liver on ultrasound. Diagnosis was established on the clinical picture and the positive results of serological testing of antibody titres for Bartonella henselae. Both patients recovered completely within 2 months.

Feasibility study of FEC-chemotherapy with dose-intensive epirubicin as initial treatment in high-risk breast cancer.

BACKGROUND: The prognosis of patients with stage III B breast carcinoma with metastasis to the apical axillary lymph nodes is poor despite adequate local control achieved by surgery and/or radiation therapy. This study evaluated the feasibility of a dose-intensive up-front chemotherapy regimen in this subgroup of patients. PATIENTS AND METHODS: A preoperative chemotherapy regimen consisting of 3 courses of fluorouracil 500 mg/m2, dose-intensive epidoxorubicin 120 mg/m2 and cyclophosphamide 500 mg/m2 (DIE-FEC), was administered at 21-day intervals without hematopoietic growth factors to 31 patients with apex-positive disease. All patients were below 60 years of age and none had had prior chemotherapy or radiotherapy. RESULTS: Seven patients achieved clinical complete responses (23%), and 21 achieved clinical partial responses (68%); three patients had stable disease (10%), one of whom had only ductal carcinoma in situ at histopathologic evaluation, which suggested an additional response to therapy. The major toxicity was moderate bone marrow suppression with a median WBC nadir of 1650/microliters (range 500-4600). Other toxic effects were mild. CONCLUSION: DIE-FEC is well-tolerated and highly effective as up-front chemotherapy in relatively young patients with high-risk breast cancer, with a 90% (CI 74%-98%) clinical objective response rate.