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Greg Williams

Publications and source records attributed to Greg Williams.

8 recordsLinked to original sources

Pitfalls in normalization for intensity-modulated radiation therapy planning.

Three-dimensional (3D) treatment planning often involves complex combinations of beam energies, treatment fields, and beam modifying devices. Even when a plan is devised that meets many treatment-planning objectives, limitations in the planner's ability to further adjust beam characteristics may require the radiation dose prescription to be normalized to an isodose level that best covers the target volume. While these normalizations help meet the volume coverage goals, they also result in adjustment of the dose delivered to the normal tissues and must be carefully evaluated. Intensity-modulated radiation therapy (IMRT) treatment planning allows combinations of complex dose patterns, in order to achieve the desired treatment planning goals. These dose patterns are created by defining a set of treatment planning objectives and then allowing the treatment planning computer to create intensity patterns, through the use of moving multileaf collimation that will meet the requested goals. Often, when an IMRT treatment plan is created that meets many of the treatment planning goals but falls short of volume coverage requirements, the planner is tempted to apply normalization principles similar to those utilized with 3D treatment planning. Again, these normalizations help meet the volume coverage goals, but unlike 3D planning situations, may result in avoidable delivery of additional doses to the normal tissues. The focus of this study is to evaluate the effect of application of normalization for IMRT planning using multiple patient situations. Recommendations would favor re-optimization over normalization in most planning situations.

Brain Neoplasms↗

Gene transfer to respiratory epithelia with lentivirus pseudotyped with Jaagsiekte sheep retrovirus envelope glycoprotein.

A feline immunodeficiency virus (FIV)-based lentiviral vector was pseudotyped to identify envelope (env) glycoproteins that direct efficient gene transfer to pulmonary epithelia for the treatment or prevention of lung diseases. The envelope glycoprotein from the Jaagsiekte sheep retrovirus (JSRV) is a candidate under investigation. We utilized high titer FIV vector (>10(8) TU/ml) pseudotyped with the JSRV env glycoprotein (JSRVFIV) to study the transduction of polarized primary cultures of human airway epithelia and receptor/vector interactions. The reported receptor for JSRV, hyaluronidase 2 (HYAL2), is a GPI-linked protein. We expressed FLAG-tagged HYAL2 in polarized airway epithelia using an adenoviral vector and documented that the HYAL2 protein sorts predominantly to the apical surface. Of interest, the efficiency of gene transfer with apically applied JSRV-FIV was markedly less than FIV pseudotyped with VSV-G, even in Ad-HYAL2 complemented epithelia. The inefficient gene transfer with JSRV-FIV in HYAL2 complemented cells suggests that factors other than receptor abundance limit apical gene transfer efficiency with this envelope. JSRV-FIV transduced the distal lung epithelia of rabbits in vivo and transduced primary cultures of rabbit type II cells with 100-fold greater efficiency than primary cultures of rabbit tracheal cells. These data indicate that a lentivirus pseudotyped with the JSRV envelope glycoprotein transduces type II cells with greater efficiency than conducting airway epithelia and provides an example of glycoprotein-mediated cell-specific tropism within a tissue with a widely heterogeneous cell population.

Animals↗

Does the admitting officer system reduce the time taken to arrange an emergency admission to hospital?

AIM: Communication is an important feature of admitting acutely ill patients to hospital in both New Zealand and Australia. The mechanisms used to facilitate communication between the general practitioner (GP) and the admitting hospital differ between the two countries. The relative effectiveness of each of these systems has never been formally studied. Our aim was to compare the efficiency of the admitting officer system for arranging hospital admissions (used in Australia) with that of direct referral by the GP to the specialist registrar (the system used in New Zealand). METHODS: Five metropolitan hospitals of comparable size from each country were selected and the time taken to contact the relevant doctor in order to arrange admission of an acutely ill patient was documented. RESULTS: A total of 120 contact attempts were made, 60 in each country. The total time taken to contact the admitting doctor in order to arrange an emergency assessment for a patient was significantly longer in New Zealand than it was in Australia (p <0.05). CONCLUSIONS: When arranging an emergency patient assessment for a patient in the community, the total time taken to contact the appropriate doctor is less in Australia, where the admitting officer system is used, than it is in New Zealand, using the specialist registrar system. Consideration should be given by acute hospitals in New Zealand to streamlining their communications processes in order to minimise delays to referring doctors and their patients.

Australia↗

Forward planning using multileaf collimation as a replacement for patient tissue compensation.

In treatment planning, a dosimetrist may encounter a technique that would best be treated by including some type of compensation to correct for tissue or depth variations throughout the field, allowing for a more homogeneous dose distribution. Recent innovations, such as intensity-modulated radiotherapy (IMRT), have been introduced in an effort to address these issues. In many institutions, however, the treatment planning capabilities available may not accommodate consideration of such new technologies. The treatment planner is therefore left to determine how to incorporate these concepts with the current technologies available. While compensation may be an option, this may not always be possible due to the position of the beam or to actual mechanical restraints. Some institutions may also lack the ability and equipment to consider compensation at all. The answer is forward planning IMRT. This concept combines current forward planning techniques with multiple asymmetrically blocked treatment fields, varying the intensity of the beam from a given orientation to produce the desired treatment plan.

Humans↗

Dose calculation errors due to inaccurate representation of heterogeneity correction obtained from computerized tomography.

Computerized tomography (CT) is used routinely in evaluating radiation therapy isodose plans. With the introduction of 3D algorithms such as the voxel raytrace, which determines inhomogeneity corrections from actual CT Hounsfield numbers, caution must be used when evaluating isodose calculations. Artifacts from contrast media and dental work, radiopaque markers placed by the treatment planner, and changing bowel and rectal air patterns all have the potential to introduce error into the calculation due to inaccurate assessment of high or low density. Radiopaque makers such as x-spot BB's or solder wire are placed externally on the patient. Barium contrast media introduced at the time of simulation may be necessary to visualize specific anatomical structures on the CT images. While these localization and visualization tools may be necessary, it is important to understand the effects they may introduce in the planning process. Other problems encountered are patient specific and out of the control of the treatment planner. These include high- and low-density streaking caused by dental work, which produce computational errors due to overestimation, and small bowel and rectal air, the patterns of which change on a daily basis and may result in underestimation of structure density. It is important for each treatment planner to have an understanding of how this potentially tainted CT information may be applied in dose calculations and the possible effects they may have. At our institution, the voxel raytrace calculation is automatically forced any time couch angle is introduced. Errors in the calculation from the above mentioned situations may be introduced if a heterogeneity correction is applied. Examples of potential calculation errors and the magnitude of each will be discussed. The methods used to minimize these errors and the possible solutions will also be evaluated.

Artifacts↗

Measles virus preferentially transduces the basolateral surface of well-differentiated human airway epithelia.

Measles virus (MV) is typically spread by aerosol droplets and enters via the respiratory tract. The progression of MV infection has been widely studied; yet, the pathway for virus entry in polarized human airway epithelia has not been investigated. Herein we report the use of a replication-competent Edmonston vaccine strain of MV expressing enhanced green fluorescent protein (MV-eGFP) to infect primary cultures of well-differentiated human airway epithelia. Previous studies with polarized Caco-2 cells (intestine-derived human epithelia) and MDCK cells (kidney-derived canine epithelia) demonstrated that MV primarily infected and exited the apical surface. In striking contrast, our results indicate that MV preferentially transduces human airway cells from the basolateral surface; however, virus release remains in an apical direction. When MV-eGFP was applied apically or basolaterally to primary cultures of airway epithelia, discrete foci of eGFP expression appeared and grew; however, the cell layer integrity was maintained for the duration of the study (7 days). Interestingly, utilizing immunohistochemistry and confocal microscopy, we observed widespread expression of the receptor for the vaccine strain of MV (CD46) at greatest abundance on the apical surface of the differentiated human airway epithelia as well as in human tracheal tissue sections. These data suggest that the progression of MV infection through the respiratory epithelium may involve pathways other than direct binding and entry through the apical surface of airway epithelia.

Antigens, CD↗

Misdiagnosis of burns: herpes zoster ophthalmicus.

Many conditions can mimic the presentation of burns. We present an interesting case in which the initial diagnosis of a chemical burn was later confirmed to be herpes zoster ophthalmicus.

Acyclovir↗