Measurements of prednisolone and some of its metabolites, in urine of patients after orthotopic liver transplantation, as a means of monitoring prednisolone absorption

In patients who had undergone orthotopic liver transplantation, malabsorption of prednisolone or increased metabolism of prednisolone was suspected. In order to rule out this possibility, urinary prednisolone, and some of its metabolites, viz prednisone and 6 beta-hydroxyprednisolone, were determined by means of a gas chromatographic assay. To evaluate this assay aliquots of a pooled urine from several of our patients were analysed in multiplicate (n = 10). Mean prednisone, prednisolone and 6 beta-hydroxyprednisolone concentrations of 1.9 mg/l, 6.3 mg/l and 4.1 mg/l, respectively, were found with the following respective day-to-day coefficients of variation: 12.3%, 5.2% and 5.3%. Amounts of prednisolone metabolites excreted in the urine of these patients were correlated with the ingested daily dose of prednisolone. It was concluded that overall absorption of prednisolone in these patients was adequate and not influenced by shortage of bile acids in the gastro-intestinal tract, or by steatorrhoea, both caused by external bile drainage. In addition there was no evidence for increased metabolism of prednisolone.     

The in-air scattering of clinical electron beams as produced by accelerators with scanning beams and diaphragm collimators

The electron distribution F(x, y, z, theta x, theta y) in air has been evaluated for a clinical electron beam emanating from a scanning beam accelerator in which the collimation of the beam is performed by means of diaphragm collimators. The multiple scattering theory of Fermi turns out to be adequate in describing this electron distribution. In this theory, the only parameter to be determined experimentally is the angular variance at the level of the collimator blocks. Generally, this angular variance features the same energy dependence as the angular scattering power and its value at an arbitrary energy can be derived from measuring the penumbra widths of off-axis profiles in air, at various distances beyond the collimator blocks. Then, the angular variance at the level of a secondary diaphragm collimator can be calculated, as well as off-axis profiles in air at arbitrary distances. In this way, the relative electron distribution at the surface of patients can be calculated easily. This in turn serves adequately as input to the calculation of patient dose distributions in radiation therapy planning.     

Effectiveness of couch height-based patient set-up and an off-line correction protocol in prostate cancer radiotherapy

PURPOSE: To investigate set-up improvement caused by applying a couch height-based patient set-up method in combination with a technologist-driven off-line correction protocol in nonimmobilized radiotherapy of prostate patients. METHODS AND MATERIALS: A three-dimensional shrinking action level correction protocol is applied in two consecutive patient cohorts with different set-up methods: the traditional "laser set-up" group (n = 43) and the "couch height set-up" group (n = 112). For all directions, left-right, ventro-dorsal, and cranio-caudal, random and systematic set-up deviations were measured. RESULTS: The couch height set-up method improves the patient positioning compared to the laser set-up method. Without application of the correction protocol, both systematic and random errors reduced to 2.2-2.4 mm (1 SD) and 1.7-2.2 mm (1 SD), respectively. By using the correction protocol, systematic errors reduced further to 1.3-1.6 mm (1 SD). One-dimensional deviations were within 5 mm for >90% of the measured fractions. The required number of corrections per patient in the off-line correction protocol was reduced significantly during the course of treatment from 1.1 to 0.6 by the couch height set-up method. The treatment time was not prolonged by application of the correction protocol. CONCLUSIONS: The couch height set-up method improves the set-up significantly, especially in the ventro-dorsal direction. Combination of this set-up method with an off-line correction strategy, executed by technologists, reduces the number of set-up corrections required.     

Numerical calculation of energy deposition by high-energy electron beams: III. Three-dimensional heterogeneous media

The phase space time evolution model of Huizenga and Storchi and Morawska-Kaczyńska and Huizenga has been modified to accommodate calculations of energy deposition by arbitrary electron beams in three-dimensional heterogeneous media. This is a further development aimed at the use of the phase space evolution model in radiotherapy treatment planning. The model presented uses an improved method to control the evolution of the phase space state. This new method results in a faster algorithm, and requires less computer memory. An extra advantage of this method is that it allows the pre-calculation of information, further reducing calculation times. Typical results obtainable with this model are illustrated with the cases of (i) a 20 MeV pencil beam in a water phantom, (ii) a 20 MeV 5 x 5 cm2 beam in a water phantom containing two air cavities, and (iii) a 20 MeV 5 x 5 cm2 beam in a water phantom containing an aluminium region. The results of the dose distribution calculations are in good agreement with and require significantly less computation time than results obtained with Monte Carlo methods.     

Isolation and partial characterization of a surface glycoconjugate of Entamoeba histolytica.

To study surface molecules of Entamoeba histolytica we produced monoclonal antibodies from mice immunized with lysates from the pathogenic amebic strain HM1:IMSS, and screened them for the ability to inhibit E. histolytica adhesion. One monoclonal antibody, CC 8.6, was a potent inhibitor of amebic adhesion to a Chinese hamster ovary cell line, and was capable of inhibiting HM1:IMSS mediated cytotoxicity by 50%. We found that monoclonal antibody CC 8.6 bound to an amebic glycoconjugate. The glycoconjugate is present only in E. histolytica and not in other Entamoeba sp. It migrates as a polydisperse band on SDS-PAGE, and can be metabolically radiolabeled with [14C]glucose, [32P]phosphate, and [3H]palmitate. The glycoconjugate can be purified by hydrophobic interaction chromatography on octyl-Sepharose; enzymatic hydrolysis with phosphatidylinositol-specific phospholipase C alters the hydrophobic properties of the molecule. HPLC analysis of [14C]glucose-labeled glycoconjugate saccharides revealed that approximately 82% of the incorporated label was in glucose and 12% in galactose. Our studies demonstrate that one of the immunogenic surface molecules of E. histolytica is a phosphorylated, lipid-containing, glycoconjugate, and that antibodies to this antigen may have the potential to protect against E. histolytica adhesion and cytotoxicity.     

Scattered radiation from applicators in clinical electron beams

In radiotherapy with high-energy (4-25 MeV) electron beams, scattered radiation from the electron applicator influences the dose distribution in the patient. In most currently available treatment planning systems for radiotherapy this component is not explicitly included and handled only by a slight change of the intensity of the primary beam. The scattered radiation from an applicator changes with the field size and distance from the applicator. The amount of scattered radiation is dependent on the applicator design and on the formation of the electron beam in the treatment head. Electron applicators currently applied in most treatment machines are essentially a set of diaphragms, but still do produce scattered radiation. This paper investigates the present level of scattered dose from electron applicators, and as such provides an extensive set of measured data. The data provided could for instance serve as example input data or benchmark data for advanced treatment planning algorithms which employ a parametrized initial phase space to characterize the clinical electron beam. Central axis depth dose curves of the electron beams have been measured with and without applicators in place, for various applicator sizes and energies, for a Siemens Primus, a Varian 2300 C/D and an Elekta SLi accelerator. Scattered radiation generated by the applicator has been found by subtraction of the central axis depth dose curves, obtained with and without applicator. Scattered radiation from Siemens, Varian and Elekta electron applicators is still significant and cannot be neglected in advanced treatment planning. Scattered radiation at the surface of a water phantom can be as high as 12%. Scattered radiation decreases almost linearly with depth. Scattered radiation from Varian applicators shows clear dependence on beam energy. The Elekta applicators produce less scattered radiation than those of Varian and Siemens, but feature a higher effective angular variance. The scattered radiation decreases somewhat with increasing field size and is spread uniformly over the aperture. Experimental results comply with the results of simulations of the treatment head and electron applicator, using the BEAM Monte Carlo code, and Siemens, but feature a higher effective angular variance. The scattered radiation decreases somewhat with increasing field size and is spread uniformly over the aperture. Experimental results comply with the results of simulations of the treatment head and electron applicator, using the BEAM Monte Carlo code.     

Optimization of multileaf collimator settings for radiotherapy treatment planning

Multileaf collimators have become available in many radiotherapy treatment centres. The cross section of a beam can be shaped to a projection of the target area by moving the leaves of the multileaf collimator into the beam. In this paper, a method is described to optimize the positions of the individual leaves automatically, once the beam directions and weights have been chosen. The individual positions of the leaves are optimized using the variable metric method. Changes in dose resulting from small leaf movements are computed efficiently using a special method. The optimization method was tested on a treatment plan for a phantom patient. It was found that the unnecessary edges of the beams were trimmed efficiently.     

Convex reformulation of biologically-based multi-criteria intensity-modulated radiation therapy optimization including fractionation effects

Finding fluence maps for intensity-modulated radiation therapy (IMRT) can be formulated as a multi-criteria optimization problem for which Pareto optimal treatment plans exist. To account for the dose-per-fraction effect of fractionated IMRT, it is desirable to exploit radiobiological treatment plan evaluation criteria based on the linear-quadratic (LQ) cell survival model as a means to balance the radiation benefits and risks in terms of biologic response. Unfortunately, the LQ-model-based radiobiological criteria are nonconvex functions, which make the optimization problem hard to solve. We apply the framework proposed by Romeijn et al (2004 Phys. Med. Biol. 49 1991-2013) to find transformations of LQ-model-based radiobiological functions and establish conditions under which transformed functions result in equivalent convex criteria that do not change the set of Pareto optimal treatment plans. The functions analysed are: the LQ-Poisson-based model for tumour control probability (TCP) with and without inter-patient heterogeneity in radiation sensitivity, the LQ-Poisson-based relative seriality s-model for normal tissue complication probability (NTCP), the equivalent uniform dose (EUD) under the LQ-Poisson model and the fractionation-corrected Probit-based model for NTCP according to Lyman, Kutcher and Burman. These functions differ from those analysed before in that they cannot be decomposed into elementary EUD or generalized-EUD functions. In addition, we show that applying increasing and concave transformations to the convexified functions is beneficial for the piecewise approximation of the Pareto efficient frontier.     

A scintillating gas detector for 2D dose measurements in clinical carbon beams

A two-dimensional position sensitive dosimetry system based on a scintillating gas detector has been developed for pre-treatment verification of dose distributions in hadron therapy. The dosimetry system consists of a chamber filled with an Ar/CF(4) scintillating gas mixture, inside which two cascaded gas electron multipliers (GEMs) are mounted. A GEM is a thin kapton foil with copper cladding structured with a regular pattern of sub-mm holes. The primary electrons, created in the detector's sensitive volume by the incoming beam, drift in an electric field towards the GEMs and undergo gas multiplication in the GEM holes. During this process, photons are emitted by the excited Ar/CF(4) gas molecules and detected by a mirror-lens-CCD camera system. Since the amount of emitted light is proportional to the dose deposited in the sensitive volume of the detector by the incoming beam, the intensity distribution of the measured light spot is proportional to the 2D hadron dose distribution. For a measurement of a 3D dose distribution, the scintillating gas detector is mounted at the beam exit side of a water-bellows phantom, whose thickness can be varied in steps. In this work, the energy dependence of the output signal of the scintillating gas detector has been verified in a 250 MeV/u clinical (12)C ion beam by means of a depth-dose curve measurement. The underestimation of the measured signal at the Bragg peak depth is only 9% with respect to an air-filled ionization chamber. This is much smaller than the underestimation found for a scintillating Gd(2)O(2)S:Tb ('Lanex') screen under the same measurement conditions (43%). Consequently, the scintillating gas detector is a promising device for verifying dose distributions in high LET beams, for example to check hadron therapy treatment plans which comprise beams with different energies.