BackgroundThe efficacy of paclitaxel-coated balloons (PCB) for restenosis prevention has been demonstrated in humans. However, the mechanism of action for sustained drug retention and biological efficacy following single-time drug delivery is still unknown.Methods and resultsThe pharmacokinetic profile and differences in drug concentration (vessel surface vs arterial wall) of two different paclitaxel coating formulations (3 µg/mm2) displaying opposite solubility characteristics (CC=crystalline vs AC=amorphous) were tested in vivo and compared with paclitaxel-eluting stents (PES). Also, the biological effect of both PCB formulations on vascular healing was tested in the porcine coronary injury model. One hour following balloon inflation, both formulations achieved similar arterial paclitaxel levels (CC=310 vs AC=245 ng/mg; p=NS). At 24 h, the CC maintained similar tissue concentrations, whereas the AC tissue levels declined by 99% (p<0.01). At this time point, arterial levels were 20-fold (CC) and 5-fold (AC) times higher compared to the PES group (p<0.05). At 28 days, arterial levels retained were 9.2% (CC) and 0.04% (AC, p<0.01) of the baseline levels. Paclitaxel concentration on the vessel surface was higher in the CC at 1 (CC=36.7% vs AC=13.1%, p<0.05) and 7 days (CC=38.4% vs AC=11%, p<0.05). In addition, the CC induced higher levels of neointimal inhibition, fibrin deposition and delayed healing compared with the AC group.ConclusionsThe presence of paclitaxel deposits on the vessel surface driving diffusion into the arterial tissue in a time-dependent fashion supports the mechanism of action of PCB. This specific pharmacokinetic behaviour influences the patterns of neointimal formation and healing.

Abstract. We have mapped the catchment region of Pine Island Glacier, Antarctica, using ERS-1 and ERS-2 radar altimetry and synthetic aperture radar (SAR) interferometry. The radar altimeter data were converted to a digital elevation model (DEM), using an algorithm we developed that corrects for slopes and grids the surface elevation estimates in a single step. We used the DEM and precise (postprocessed) orbital ephemerides to generate terrain-corrected and geolocated complex radar imagery. Interferometric pairs on both ascending and descending orbits, corrected by means of the DEM, yielded components of ice surface motion in the radar look direction. Where possible, we combined velocity components from ascending and descending tracks to produce vector velocities; elsewhere, the velocity was calculated by assuming the direction of motion is down the surface slope. The velocity map reveals a system of tributaries that channel ice from the basin-like catchment area into the fast flowing downstream trunk of Pine Island Glacier. None of the tributaries shows a clear onset region. Instead, the ice speed gradually increases, along with a gradual decrease in driving stress, along each tributary. We combined the velocity data with sparse information on ice thicknesses and snow accumulation rates to calculate an approximate mass balance. We find that the region is in balance within an uncertainty of -30% of the total mass throughput. With centimeter wavelengths the InSAR phase difference is sensitive to surface displacements of only a few millimeters. , Unfortunately, other sources of interferometric phase shift can contaminate the ice motion measurements. These include unmodeled topography, errors in satellite ephemerides, and atmospheric changes between visits. The first two sources are related, in that the interferometric baseline must be known in order to remove the effect of the surface topography. We have produced, from radar altimetry, a DEM of our region of interest that we believe is sufficiently accurate (because short interferometric baselines are available) to correct adequately 21,761

In the experimental setting, second-generation PCB showed a comparable efficacy profile and more favorable vascular healing response when compared to first-generation PCB. The clinical implications of these findings require further investigation.

In the FHS coronary injury model, BMS implantation using a PCB yields a degree of neointimal inhibition comparable to the PES. The BMS+PCB combination presented lower degrees of inflammation and fibrin deposition; however, signs of delayed healing were still present.

Paclitaxel delivery to porcine ilio-femorals using PCB followed by BMS implantation effectively decreased neointimal proliferation. More extensive and prolonged proliferative response of the vessel after stenting (necessitating higher drug dose) could potentially explain the undetectable effect of PEBx1 relative to CCBx1 in this pilot study. Histological analysis confirmed the safety and biocompatibility of PCB technology.

The FHS model of iliofemoral ISR demonstrated a dose-dependent effect on the inhibition of neointimal proliferation of a clinically validated PCB technology. This model represents a positive step toward the efficacy evaluation of PCB in the peripheral vascular territory.

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A satellite radar altimeter can be used to monitor surface elevation change over polar ice sheets. Thirty-five months of Geosat Exact Repeat Mission (ERM) data from November 1986 to September 1989 over a section of East Antarctica (69–72.1 ∘S, 80–140∘ E) have been used in this study. A model that considers both surface and volume scattering was used to retrack the altimeter waveforms. Surface elevations for each month after the first three were compared to the average elevations for the first 3 months through a crossover method. The averaged crossover elevation difference changed with time in a way that suggests a yearly cycle in surface elevation. The average amplitude of the cycle is about 0.6 m. We have been unable to find any satisfactory explanation for the observed changes, in terms of either sources of error or contributors to real surface-height changes. We strongly suspect that orbit error plays a major role in producing the variations, although we know of no quantitatively satisfactory source of a quasi-seasonal variation in orbit error. Other possible contributors include a real seasonal variation in accumulation rate, seasonal changes in the delay of the radar signal as it propagates through the atmosphere, unmodeled variations in the depth of penetration of the radar pulse into the firn, changes in the thickness of the ice and the firn zone in response to seasonal variations in pressure and temperature, and the inverted barometer effect. Even though we do not know the cause of the variations, the results show the importance of comparing elevations at the same time of year for observations that are not continuous, while at the same time showing that even annually spaced measurements may not be free of substantial errors associated with interannual variability. The quasi-periodic variations obscure any evidence of a moderate secular change in surface height, if there is one, but a dramatic lowering at rates approaching 1 ma–1, such as are known elsewhere in Antarctica, can definitely be ruled out.