Bibliothek

Notizen: Abstract We have recently shown that the angiotensin I converting enzyme (ACE) gene is linked to NaCl-loaded blood pressure in the stroke-prone spontaneously hypertensive rat (SHRSP), and that high-NaCl loading selectively stimulates ACE in the aorta of SHRSP but not in normotensive Wistar-Kyoto (WKY) rats. We therefore investigated the relationship between cardiac ACE and the development of hypertension and left ventricular hypertrophy in response to normal- and high-NaCl diet in these rats. ACE mRNA and ACE activity were measured in left ventricular tissue after completion of hemodynamic characterization of the animals. While SHRSP rats increased blood pressure (P〈0.0001) and heart rate (P〈0.005) in response to high NaCl, blood pressure remained unchanged in WKY. Similarly, relative left ventricular weight increased only in SHRSP after high NaCl (P〈0.002). A significant two- to threefold increase of cardiac ACE mRNA and fourfold stimulation of ACE enzyme activity in response to high NaCl was found in both WKY and SHRSP rats (P〈0.005). The induction of ACE gene expression was significantly more pronounced in SHRSP compared to WKY (P〈0.02), whereas no significant strain differences in left ventricular ACE activity were found after either normal- or high-NaCl diet. Thus, arterial blood pressure and left ventricular weight remained unchanged in the WKY rats despite the activation of left ventricular ACE activity after high-NaCl exposure. These results demonstrate that left ventricular ACE activity is equally upregulated in response to high-NaCl in the normotensive and hypertensive strain, independently from the development of hypertension. We conclude that the pretranslational induction of left ventricular ACE with high-NaCl loading may be important both for the regulation of cardiac angiotensins and kinins and for local therapeutic ACE inhibition in the heart during high-salt status.

Notizen: Abstract Recently the use of stereotactic radiosurgery to treat functional disorders such as Parkinson's disease, epilepsy, and intractable pain has been reported in the literature. In such applications, a large single dose is typically delivered to an extremely small (〈0.05 cm3) target volume. The purpose of this work is to investigate whether the dosimetric and imaging characteristics of radiosurgery treatment planning provide sufficient accuracy to allow efficacious therapy of functional disorders. We have begun treating trigeminal neuralgia using our linear accelerator-based radiosurgery system: 70 Gy is prescribed to the maximum dose in the volume (in our case the 100% isodose level) and delivered to the base of the fifth nerve in a single fraction using a 5 mm collimator, with the standard Brown–Roberts–Wells (BRW) radiosurgery accessories employed for fixation and localization. Because the fifth nerve cannot be visualized on x-ray computed tomography (CT), our radiosurgery treatment planning system was modified to use magnetic resonance images for localization, though dose calculations are still performed using CT. Isocentric accuracy of our original radiosurgery system, consisting of a floor stand and isocentric subunit, and our new couch mount system, was evaluated using the Winston–Lutz film test method. In order to evaluate the spatial accuracy of magnetic resonance (MR) treatment planning, eight 4 mm sections of a 7 French catheter were filled with CuSO4 contrast material and attached rigidly to the stereotactic fixation posts of our BRW frame, four each in orientations parallel and perpendicular to the axial plane. The position of the externally placed fiducial markers, as well as internal anatomical structures, were then compared with CT. Monte Carlo calculations were compared with those from a commercial radiosurgery treatment planning system in order to investigate the effects of tissue heterogeneities on the resulting dose distributions. While commercial radiosurgery systems assume tissue homogeneity, the Monte Carlo calculations were performed in a patient-specific CT geometry accounting for all tissue inhomogeneities. The resulting 128 × 128 Monte Carlo dose grid was superimposed on the original CT data for analysis and comparison with identical treatment plans from the commercial system. The ability of our LINAC-based systems to accurately target a desired point in space has been effectively demonstrated: 0.32 ± 0.32 mm (N = 556) for our floor stand system and 0.34 ± 0.23 mm (N = 50) for our newer couch-mounted system. Inaccuracies introduced by tomographic imaging devices are significantly greater. The use of gel-filled fiducial markers in magnetic resonance imaging (MRI) guided radiosurgery produces significant spatial distortion, resulting in Euclidean root-mean-square deviations of 2.32 ± 0.96 mm (N = 31) and 3.64 ± 1.28 mm (N = 27) at the center and periphery (extracranial) of the field of view respectively, as compared with CT. Use of water of CuSO4 filled rods had a minimal effect on these deviations: 2.51 ± 1.25 mm (N = 31) and 3.37 ± 1.28 mm (N =27) for central and peripheral targets respectively. Magnetic susceptibility artifacts in the frequency encoding (AP) direction produce a systematic posterior shift. This together with axial slice spacing accounts for the majority of the deviation. Tissue heterogeneities such as bone and air cavities produce a lateral spreading of the dose from small photon beams, resulting in a prescription dose volume smaller than predicted by conventional treatment planning systems. For a typical are configuration designed to produce a spherical dose volume, Monte Carlo calculations show the 90% dose volume to be significantly smaller than that predicted by the commercial system when either 5 mm or 10 mm collimators are used. Use of a LINAC-based system does not preclude accurate treatment of small functional targets. Isocentric uncertainty for either of two LINAC systems that we evaluated is small compared to imaging and dosimetric factors. However, chemical shifts and object-induced magnetic susceptibility artifacts can produce systematic spatial distortions in magnetic resonance images; thus, MR imaging may not possess the inherent accuracy necessary for stereotactic localization and targeting of small cranial structures. In addition, both CT and MR possess an inherent inaccuracy of at least one-half of the axial slice thickness; thus, for localization purposes, a slice spacing as small as possible should be used when treating small targets. Tissue heterogeneities decrease the volume covered by the higher isodose lines. As a result, the target may be only partially covered by the intended dose level, with the remainder lying in the high gradient region. This same lateral spreading may also increase the risk to adjacent normal structures. Imaging and dosimetric considerations are not unique to linear accelerator systems but apply equally to all stereotactic photon irradiation. Until spatial and dosimetric errors can be accounted for, use of a larger collimator will ensure better coverage of small targets.

Notizen: Abstract Fractionated stereotactic radiation therapy is a useful new approach for treating a number of intracranial neoplasms including meningiomas, pituitary adenomas, craniopharyngiomas, and recurrent gliomas. For the majority of these we employ a conventional fractionation scheme of 180 cGy per fraction for 25 to 30 fractions, using a modified Gill–Thomas–Cosman (GTC) relocatable frame to accommodate fractionated delivery. The GTC system uses a custom acrylic dental appliance to set the frame position and an occipital plate and Velcro straps fix the head in place. Daily reproducibility is evaluated through use of a “depth helmet,” a plastic hemispherical shell containing 25 holes at regularly spaced intervals. The depth helmet attaches to the GTC frame and the distance from the shell to the patient's head is recorded at each of the 25 positions. This paper describes a new simplified approach to the quantitative assessment of day-to-day variability in head fixation using the depth helmet measurements. This approach avoids the need to try and decide on the relative merit of 25 numerical differences at each fitting and provides a straightforward mathematical and conceptual framework for the description of fit and clinical decision making. The mathematical analysis and computer program we have developed uses all 25 measurements to provide a single three-dimensional displacement vector as well as displacement values in the three principal patient dimensions. Measurements at each of the 25 depth helmet positions are automatically separated into three principal axes corresponding to the patients left/right (x), anterior/posterior (y), and superior/inferior (z) using the spherical relations: x = r sin(Φ) cos(θ), y = r sin(Φ) sin(θ), z = r cos(Φ), where θ and Φ are the polar and azimuthal angles respectively and ris the distance from the center of the depth helmet to the surface of the patient's head. For each patient, a set of initial measurements is taken at the CT scanner with the patient in the treatment (supine) position. Because treatment planning is based on the CT scan, this serves as the baseline from which subsequent deviations are recorded. In an analysis of our first 30 patients representing over 750 fractions, the mean RMS deviation, that is, the mean three-dimensional displacement from baseline, was 0.468 ± 0.296 mm. Among individual patients the range was 0.169 mm to 1.438 mm. A closer analysis suggests that in-plane (AP/PA-lateral) deviations occur randomly. Deviations along the superior/inferior direction are greater than those in-plane, and in several patients a small shift along this axis, possibly due to a loosening or stretching of the Velcro straps, has been noted over time. We have found our method to be a useful indicator of day-to-day reproducibility, allowing ready identification and correction of three-dimensional shifts relative to the patient axes. Based on our initial analysis, we can now define quantitative limits of acceptability in repositioning for subsequent fractionated delivery.

Notizen: Titration calorimetric data show a dramatic change from endo- to exothermic deaggregation when pentanol-hexadecyltrimethylammonium bromide (CTAB) mixed solutions are injected into an aqueous solution containing pentanol. The results are interpreted in terms of a change in the structures of the aggregates in solution from simple CTAB micelles to mixed amphiphilic microheterogeneities when pentanol is added.