Cragg Endopro System I: early experience. I. Femoral arteries.

PURPOSE: This work describes the early experience with the Cragg Endopro System I. The safety and efficacy of this device in the treatment of atherosclerotic lesions of the femoral arteries are evaluated. MATERIALS AND METHODS: Eleven patients with complex femoral artery lesions were treated. Ten patients presented with femoral artery occlusion and one had a 90% stenosis. All patients had life-style limiting claudication. Associated comorbid states included smoking (n = 10), hypertension (n = 4), hyperlipidemia (n = 5), coronary artery disease (n = 3), and diabetes (n = 1). The stents were dilated to the size of the native artery in the first three patients. The protocol was modified and stents were overdilated by 1 mm in the remaining eight patients. An anticoagulation regimen was used in the first three patients and modified per protocol requirements in the remaining eight. Prophylactics antibiotics were given before the procedure. Follow-up studies included Doppler ultrasound and intravenous and intraarterial digital subtraction angiography. RESULTS: An antegrade femoral approach was used. Stent placement was successful in all patients. The mean lesion length was 9.9 cm (4-18 cm). Mean ankle/brachial index before treatment was 0.65 and increased to 0.87 after treatment. Mean follow-up was 17.2 months, and one patients was lost to follow-up. Complications included sepsis (n = 1), fever (n = 2), severe pain (n = 4), thrombosis (n = 5), and hematoma (n = 2). Stent patency was improved after protocol modifications. Overall primary patency rate was 45% and secondary patency was 56%. CONCLUSION: This early experience with the Cragg Endopro System I shows that recanalization of long femoral occlusions and stent-graft placement is feasible. The primary and secondary patency rates are low and the complication rate is high. Improved patency rates are expected with a more aggressive anticoagulation regimen and stent overdilation.

Early PDGF-induced alterations in cytosolic free calcium are required for mitogenesis.

Early alterations in cytosolic free Ca2+ concentration (Ca2+i) (occurring within seconds to minutes) following platelet-derived growth factor (PDGF) stimulation were demonstrated to be required, in both BALB/c3T3 fibroblasts and vascular smooth muscle cells, for subsequent DNA synthesis by introduction of Ca(2+)-antagonists at different times in relation to growth factor stimulation. Blockade of PDGF-stimulated increases in Ca2+i correlated with inhibition of PDGF-stimulated DNA synthesis in both systems, although the mechanism of increased Ca2+i is different in the two cell types. In vascular smooth muscle cells, voltage-sensitive Ca(2+)-channel antagonists, TPA, and pertussis toxin inhibited both PDGF-induced increases in Ca2+i and DNA synthesis when added immediately before PDGF, but did not do so when added for the same time period 4 hr after PDGF. Similarly, pretreatment of fibroblasts with TMB-8 inhibited PDGF-induced alterations in Ca2+i and DNA synthesis, but had no effect on DNA synthesis when added after PDGF exposure. These findings demonstrate for the first time that early increases in Ca2+i stimulated by PDGF play a critical role in PDGF-stimulated mitogenesis.

Selective activity of 5-fluoroorotic acid against Plasmodium falciparum in vitro.

Unlike mammalian cells, malarial parasites are completely dependent on de novo pyrimidine metabolism. Even though these parasites do not use external uracil or uridine, orotic acid, an intermediate of pyrimidine biosynthesis, is successfully transported into the parasite and incorporated into parasite nucleic acids. On this basis, it was hypothesized that 5-fluoroorotate, a cytotoxic derivative of orotic acid, may be a potent and selective antimalarial agent. In vitro, 5-fluoroorotate caused 50% inhibition of the growth of Plasmodium falciparum at a concentration of 6.0 nM. In contrast, 5-fluorouracil, 5-fluorouridine, and 5-fluoro 2'-deoxyuridine were much less effective against malarial parasites. Chloroquine-susceptible and chloroquine-resistant clones of P. falciparum were equally susceptible to 5-fluoroorotate. The toxicity of 5-fluoroorotate was evaluated on four human cell lines (HT-1080, IMR-90, HeLa S3, and HL-60) and one mouse cell line (L-1210). Compared with malarial parasites, the mammalian cells were relatively tolerant of 5-fluoroorotic acid (50% inhibitory concentration, 0.9 to 10 microM). Finally, in the presence of 1 mM uridine, all mammalian cells were partially protected from 5-fluoroorotate cytotoxicity, but uridine offered no protection to P. falciparum.