An implementation strategy for IMRT of ethmoid sinus cancer with bilateral sparing of the optic pathways.

PURPOSE: To develop a protocol for the irradiation of ethmoid sinus cancer, with the aim of sparing binocular vision; of developing a strategy of intensity-modulated radiation therapy (IMRT) planning that produces dose distributions that (1) are consistent with the protocol prescriptions and (2) are deliverable by static segmental IMRT techniques within a 15-minute time slot; of fine tuning the implementation strategy to a class solution approach that is sufficiently automated and efficient, allowing routine clinical application; of reporting on the early clinical implementation involving 11 patients between February 1999 and July 2000. patients and methods: Eleven consecutive T1-4N0M0 ethmoid sinus cancer patients were enrolled in the study. For Patients 1-8, a first protocol was implemented, defining a planning target volume prescription dose of 60 to 66 Gy in 30-33 fractions and a maximum dose (Dmax) of 50 Gy to optic pathway structures and spinal cord and limit of 60 Gy to brainstem. For Patients 9-11, an adapted (now considered mature) protocol was implemented, defining a (planning target volume) prescription dose of 70 Gy in 35 fractions and a Dmax to optic pathway structures and brainstem of 60 Gy and to spinal cord of 50 Gy. RESULTS: The class solution-directed strategy developed during this study reduced the protocol translation process from a few days to about 2 hours of planner time. The mature class solution involved the use of 7 beam incidences (20-37 segments), which could be delivered within a 15-minute time slot. Acute side effects were limited and mild. None of the patients developed dry eye syndrome or other visual disturbances. The follow-up period is too short for detection of retinopathy or optic nerve and chiasm toxicity. CONCLUSION: Conventional radiotherapy of ethmoid sinus tumors is associated with serious morbidity, including blindness. We hypothesize that IMRT has the potential to save binocular vision. The dose to the optic pathway structures can be reduced selectively by IMRT. Further enrollment of patients and longer follow-up will show whether the level of reduction tested by the clinical protocol is sufficient to save binocular vision. An adaptive strategy of IMRT planning was too inefficient for routine clinical practice. A class solution-directed strategy improved efficiency by eliminating human trial and error during the IMRT planning process.

Postoperative radiotherapy of paranasal sinus tumours: a challenge for intensity modulated radiotherapy.

BACKGROUND AND PURPOSE: Intensity modulated radiotherapy (IMRT) is used in our department for treatment of paranasal sinuses. We describe the methodology that was developed together with the clinical implementation, illustrated by a case report. MATERIAL AND METHODS: Patient history, treatment and short follow-up are described. An IMRT, obtained by superposition of static beam segments was implemented. Electronic portal images, compared to digitally reconstructed radiographs (DRR) were used to evaluate and adjust patient positioning. RESULTS, DISCUSSION AND CONCLUSION: IMRT is an appropriate and feasible treatment technique for head and neck cancer in anatomical regions that are difficult to treat. A high tumour dose can be combined with a good sparing of the surrounding organs at risk (OAR's).

Agrobacterium rhizogenes-mediated transformation of Echinacea purpurea.

Echinacea purpurea seedlings were inoculated with several Agrobacterium rhizogenes strains in order to obtain hairy roots. Infection with A. rhizogenes strains LMG63 and LMG150 resulted in callus formation. Upon infection with strains ATCC 15834 and R1601 hairy roots were obtained. Opine detection confirmed transformation of E. purpurea. Comparative HPLC fingerprint analysis of the alkamides from natural plant source, control tissues, and transformed callus and roots indicated that transformed callus and hairy roots might be a promising source for continuous and standardized production of the dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamide and related amides.

Quantification of ethylene chlorohydrin and ethylene glycol as potential reaction products in gas-sterilized medical-grade plastics.

A gas chromatographic procedure is described for the quantitative determinations of ethylene chlorohydrin and ethylene glycol in disposable medical-grade plastics. Both components are isolated by solvent extraction. The lower limit of detection is 1 p.p.m. of ethylene chlorohydrin and 2 p.p.m. of ethylene glycol. Propylene glycol is used as an internal standard. Ethylene oxide residues have to be removed prior to the assay.

Polymorphic behaviour of chloroquine diphosphate.

The crystalline structure of two different batches of chloroquine diphosphate was studied. Differential thermal analysis showed the existence of two polymorphic modifications in one of the batches, whilst spectral analysis did not reveal any differences. This discrepancy is attributed to the fact that the second modification is formed during the transition phase when analysed by differential thermal analysis. This recrystallization process is initiated by the presence of seed material. The ratio of transition heat of both modifications is dependent on particle size and heating rate during analysis.

The rabbit as an experimental model for biopharmaceutical studies following rectal administration of theophylline.

In order to find a suitable animal model for biopharmaceutical studies after rectal application of theophylline, the pharmacokinetics of theophylline following the administration in rabbits of three different rectal preparations were examined and compared with those of the oral and i. v. route. No significant formulation related impact from the studied rectal dosage forms on the bioavailability of the drug was found. However, the unexpected rapid achievement of peak serum concentration after insertion of the suppository lacked any correlation with human experiments. It was concluded that the evaluation of rectal theophylline medication for man cannot directly be based on the data obtained from rabbits.

Interaction of antacids with antiarrhythmics. V. Effect of aluminium hydroxide and magnesium oxide on the bioavailability of quinidine, procainamide and propranolol in dogs.

The influence of aluminium hydroxide and magnesium oxide on the oral bioavailability of quinidine, procainamide and propranolol in the dog was investigated. The administration of aluminium hydroxide with a quinidine sulfate capsule causes a significant decrease of maximal plasma concentration (Cpmax) and a shift in tmax (time to reach Cpmax). The area under the curve is not significantly decreased. Administration of magnesium oxide together with a quinidine sulfate capsule or a sustained-release preparation of quinidine bisulfate causes a significant decrease of both Cpmax and the area under the curve. A shift of tmax was observed for the conventional preparation only. The administration of aluminium hydroxide with procainamide hydrochloride diminishes only Cpmax in a significant way. Administration of magnesium oxide together with procainamide hydrochloride has no influence on the different parameters. Administration of aluminium hydroxide or magnesium oxide with propranolol hydrochloride has a significant negative influence on both the Cpmax and the area under the curve.

Drug-polymer combinations. Part 1: The preparation of sustained release drugs by combination with ion exchanging resins.

The preparation of procainamide and propranolol resinates is described. By in vivo experiments with propranolol resinate as model substance the release rate as a function of crosslinking degree and particle size is studied. An in vitro test is carried out to compare the performance as prolonged release preparation of a resinate, e.g. procainamide resinate, with the action of the pure drug and of a Durette formulation.

Determination of plasma theophylline by straight-phase high-performance liquid chromatography: elimination of interfering caffeine metabolites.

Several authors have recently reported interference in theophylline analysis by paraxanthine (1,7-dimethylxanthine), an important metabolite of caffeine. A method for the determination of theophylline in plasma is described, eliminating caffeine and related compounds by means of straight-phase high-performance liquid chromatography. The resulting procedure is sufficiently rapid, accurate and sensitive to be applied in routine monitoring of therapeutic levels in patients as well as for pharmacokinetic purposes. Although only 0.1 ml of sample is required, concentrations as low as 0.2 mg/l can be measured with acceptable precision. A brief comparative evaluation of this procedure with a radioimmunoassay is made.

Studies on the crystalline form of phenytoin.

Two crystalline forms of phenytoin were isolated and characterized by X-ray diffraction, IR spectroscopy and differential thermal analysis. The dissolution behavior of the two forms was determined in water. The crystals of needle shape (form II) were found to exhibit slower dissolution rate than the other crystal form (form I).