Safety and efficacy of plasmid DNA expressing two isoforms of hepatocyte growth factor in patients with critical limb ischemia.

VM202, a plasmid DNA that expresses two isoforms of hepatocyte growth factor, may elicit angiogenic effects that could benefit patients with critical limb ischemia (CLI). In a phase 2, double-blind trial in 52 CLI patients, we examined the safety and potential efficacy of intramuscular injections of low-dose (n=21) or high-dose (n=20) VM202 or placebo (n=11) in the affected limb (days 0, 14, 28 and 42). Adverse events and serious adverse events were similar among the groups; no malignancy or proliferative retinopathy was seen. In exploratory efficacy analyses, we found no differences in ankle or toe-brachial index, VAS, VascuQuol or amputation rate among the groups. Complete ulcer healing was significantly better in high-dose (8/13 ulcers; P<0.01) versus placebo (1/9) patients. Clinically meaningful reductions (>50%) in ulcer area occurred in high-dose (9/13 ulcers) and low-dose (19/27) groups versus placebo (1/9; P<0.05 and P<0.005, respectively). At 12 months, significant differences were seen in TcPO2 between the high-dose and placebo groups (47.5 ± 17.8 versus 36.6 ± 24.0 mm Hg, respectively; P<0.05) and in the change from baseline among the groups (P<0.05). These data suggest that VM202 is safe and may provide therapeutic bioactivity in CLI patients.

A capillary discharge as a potential x-ray laser driver.

This paper describes a combined theoretical and experimental approach to understanding the capillary spark discharge with specific application to use as a soft x-ray or extreme ultraviolet laser source. Atomic physics calculations have identified several potential laser lines in a collisionally pumped neon-like or nickel-like plasma, and magnetohydrodynamic (MHD) modeling has shown that a capillary discharge device should be capable of producing the correct plasma conditions to achieve a population inversion in some of these lines. An experiment is constructed to evaluate the accuracy of the MHD model and investigate the potential of observing inversion in a neon-like argon or a nickel-like krypton plasma.

Measured response of multilayers to damaging fluxes.

We have measured the response of WC/C multilayers to x-ray fluxes on the order of 200 MW/cm2 using laser-generated plasmas and found that these multilayers will maintain near peak reflectivity for at least 1 ns but are eventually destroyed. A description of the experiments and data analysis methods is given. Transmission electron micrographs of WC/C multilayers before and after irradiation show melting to be the dominant damage mechanism. The results of the experiments will be compared with simulations.

Peptide-containing nerve fibres in the gut wall in Crohn's disease.

Neurones containing VIP, substance P, or enkephalin were studied by immunocytochemistry in intestinal specimens from 27 patients with Crohn's disease. Also several endocrine cell systems in the gut were examined. The results were compared with those from a control group of 26 patients. The relative frequency of various endocrine cells did not differ overtly from that in controls. Vasoactive intestinal polypeptide and substance P nerve fibres were distributed in all layers of the gut wall, including the submucosal and myenteric plexuses, whereas enkephalin fibres were restricted to the smooth muscle layer and the myenteric plexus. The distribution and frequency of the peptide-containing nerve fibres were the same in Crohn's disease patients as in control patients. A proportion of these nerve fibres, however, were notably coarse in the Crohn's disease patients. This was particularly apparent in the afflicted parts of the intestine although it was noted also in non-afflicted parts. The concentration of VIP and substance P (expressed as pmol/g wet weight) did not, however, exceed that of the control group.