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P J Biggs

Publications and source records attributed to P J Biggs.

At least 19 recordsLinked to original sources
PubMed2001

Measurement of scatter factors for 4, 6, 10, and 23 MV x rays at scattering angles between 30 degrees and 135 degrees.

NCRP Report No. 49, published in 1976, describes how to calculate the shielding for the medical use of x rays and gamma rays for energies up to 10 MV, including primary, scattered, and leakage radiation. However, in that report, data for scattered radiation for linear accelerators exist only for 6 MV, and leakage radiation is assumed, incorrectly, to be equivalent to primary radiation. Since the publication of that report, linear accelerators with energies up to 25 MV have been widely used in the radiation therapy community. Thus, there is a need to measure additional data for all energies in the range 4-25 MV. In this study, measurements were made of the "a" factor for 4, 6, 10, and 23 MV x rays at scattering angles between 30 degrees and 135 degrees. The results show that the 6 and 10 MV "a" factor data are consistent with published data, and the 23 MV data are also consistent with recently published data at 18 and 25 MV. The data show that, in general, the "a" factor decreases with energy; the exception is that 23 MV data show a sharp increase at low scattering angles, much greater than at other energies.

Scattering, Radiation↗
PubMed2000

BAC contig from a 3-cM region of mouse chromosome 11 surrounding Brca1.

Even with the completion of a draft version of the human genome sequence only a fraction of the genes identified from this sequence have known functions. Chromosomal engineering in mouse cells, in concert with gene replacement assays to prove the functional significance of a given genomic region or gene, represents a rapid and productive means for understanding the role of a given set of genes. Both techniques rely heavily on detailed maps of chromosomal regions, initially to understand the scope of the regions being modified and finally to provide the cloned resources necessary to allow both finished sequencing and large insert complementation. This report describes the creation of a BAC clone contig on mouse chromosome 11 in a region showing conservation of synteny with sequences on human chromosome 17. We have created a detailed map of an approximately 3-cM region containing at least 33 genes through the use of multiple BAC mapping strategies, including chromosome walking and multiplex oligonucleotide hybridization and gap filling. The region described is one of the targets of a large effort to create a series of mice with regional deletions on mouse chromosome 11 (33-80 cM) that can subsequently be subjected to further mutagenesis.

Animals↗
PubMed2000

Linkage and LOH studies in 19 cylindromatosis families show no evidence of genetic heterogeneity and refine the CYLD locus on chromosome 16q12-q13.

Familial cylindromatosis is an autosomal dominant predisposition to multiple neoplasms of the skin appendages. The susceptibility gene has previously been mapped to chromosome 16q12-q13 and has features of a recessive oncogene/tumour suppressor gene. We have now evaluated 19 families with this disease by a combination of genetic linkage analysis and loss of heterozygosity in cylindromas from affected individuals. All 15 informative families show linkage to this locus, providing no evidence for genetic heterogeneity. Recombinant mapping has placed the gene in an interval of approximately 1 Mb. There is no evidence, between families, of haplotype sharing that might be indicative of common founder mutations.

Carcinoma, Adenoid Cystic↗
PubMed2000

Identification of the familial cylindromatosis tumour-suppressor gene.

Familial cylindromatosis is an autosomal dominant genetic predisposition to multiple tumours of the skin appendages. The susceptibility gene (CYLD) has previously been localized to chromosome 16q and has the genetic attributes of a tumour-suppressor gene (recessive oncogene). Here we have identified CYLD by detecting germline mutations in 21 cylindromatosis families and somatic mutations in 1 sporadic and 5 familial cylindromas. All mutations predict truncation or absence of the encoded protein. CYLD encodes three cytoskeletal-associated-protein-glycine-conserved (CAP-GLY) domains, which are found in proteins that coordinate the attachment of organelles to microtubules. CYLD also has sequence homology to the catalytic domain of ubiquitin carboxy-terminal hydrolases (UCH).

Amino Acid Sequence↗
PubMed1999

AAPM's TG-51 protocol for clinical reference dosimetry of high-energy photon and electron beams.

A protocol is prescribed for clinical reference dosimetry of external beam radiation therapy using photon beams with nominal energies between 60Co and 50 MV and electron beams with nominal energies between 4 and 50 MeV. The protocol was written by Task Group 51 (TG-51) of the Radiation Therapy Committee of the American Association of Physicists in Medicine (AAPM) and has been formally approved by the AAPM for clinical use. The protocol uses ion chambers with absorbed-dose-to-water calibration factors, N(60Co)D,w which are traceable to national primary standards, and the equation D(Q)w = MkQN(60Co)D,w where Q is the beam quality of the clinical beam, D(Q)w is the absorbed dose to water at the point of measurement of the ion chamber placed under reference conditions, M is the fully corrected ion chamber reading, and kQ is the quality conversion factor which converts the calibration factor for a 60Co beam to that for a beam of quality Q. Values of kQ are presented as a function of Q for many ion chambers. The value of M is given by M = PionP(TP)PelecPpolMraw, where Mraw is the raw, uncorrected ion chamber reading and Pion corrects for ion recombination, P(TP) for temperature and pressure variations, Pelec for inaccuracy of the electrometer if calibrated separately, and Ppol for chamber polarity effects. Beam quality, Q, is specified (i) for photon beams, by %dd(10)x, the photon component of the percentage depth dose at 10 cm depth for a field size of 10x10 cm2 on the surface of a phantom at an SSD of 100 cm and (ii) for electron beams, by R50, the depth at which the absorbed-dose falls to 50% of the maximum dose in a beam with field size > or =10x10 cm2 on the surface of the phantom (> or =20x20 cm2 for R50>8.5 cm) at an SSD of 100 cm. R50 is determined directly from the measured value of I50, the depth at which the ionization falls to 50% of its maximum value. All clinical reference dosimetry is performed in a water phantom. The reference depth for calibration purposes is 10 cm for photon beams and 0.6R50-0.1 cm for electron beams. For photon beams clinical reference dosimetry is performed in either an SSD or SAD setup with a 10x10 cm2 field size defined on the phantom surface for an SSD setup or at the depth of the detector for an SAD setup. For electron beams clinical reference dosimetry is performed with a field size of > or =10x10 cm2 (> or =20x20 cm2 for R50>8.5 cm) at an SSD between 90 and 110 cm. This protocol represents a major simplification compared to the AAPM's TG-21 protocol in the sense that large tables of stopping-power ratios and mass-energy absorption coefficients are not needed and the user does not need to calculate any theoretical dosimetry factors. Worksheets for various situations are presented along with a list of equipment required.

Biophysical Phenomena↗
PubMed1999

Measurement of the collection efficiency of a large volume spherical ionization chamber in megavoltage therapy beams.

The collection efficiency of a 5.7 cm diameter spherical ionization chamber has been measured in 4 MV and 10 MV x-ray beams at various distances from the source. This chamber was found to have a substantial inefficiency due to its large volume and the high dose rate and pulsed nature of the therapy beams. It was also found that the efficiency depended on the dose rate of the machine because the inter-pulse separation time of the linac is significantly less than the ion transit-time for this chamber. Thus, ionization from more than one beam pulse is collected by the chamber at the same time. The efficiency was determined using three techniques (i) the two-voltage technique, (ii) the voltage extrapolation technique and (iii) a method originally devised for determining the collection efficiency of large volume ionization chambers in diagnostic radiology. The results show that methods (ii) and (iii) agree well, but that the two-voltage technique predicts a much lower efficiency. At about 4 m from the source, the collection efficiency for this chamber varied between 98% and 97% for dose rates between 50 and 250 cGy/min for 4 MV and between 97% and 90% for dose rates between 100 and 600 cGy/min for 10 MV. At isocenter, the comparable figures were 78% and 56% respectively for 4 MV and 65% and 38% respectively for 10 MV.

Electric Power Supplies↗
PubMed1999

Distance-dose curve for a miniature x-ray tube for stereotactic radiosurgery using an optimized aperture with a parallel-plate ionization chamber.

A recently developed miniature x-ray tube operating at 40 kV has been used in a randomized trial for the treatment of small intracranial lesions. The diameter of these lesions ranges from 10 to 30 mm. A thin window parallel-plate ionization chamber was used to calibrate the output of the x-ray tube, modified by the addition of a thin platinum aperture to reduce the charge collecting area of the chamber. The effect of such an aperture on the measurement of dose versus distance from the x-ray tube in a phantom has been examined as a function of aperture diameter. Aperture diameters were varied between 0 and 5 mm and dose measurements were made for distances between the x-ray source and the front surface of the chamber of 5-30 mm in water. The ratio of doses measured with and without an aperture, when normalized to unity at a distance of 10 mm, differs significantly from unity, for distances between 7.5 and 15 mm, for aperture diameters <1.5 mm and differs from unity, but less significantly, for apertures > or =3 mm. For intermediate diameters, however, this dose dependence is minimized, indicating an aperture diameter that provides a similar distance-dose curve as the measurement taken without an aperture over this range of distances. This diameter was found to be between 2 and 2.5 mm with a dose variation of less than +/- 1%. For distances <7.5 mm, measurements made with a 1.5-mm-diam aperture agree better with those taken with a 1.7-mm-diam chamber compared with a 5.2-mm-diam chamber.

Dose-Response Relationship, Radiation↗
PubMed1998

Evidence for a significant timer error on a linear accelerator: consequences for a special therapy application.

A significant timer error has been found on a linear accelerator used for intraoperative radiation therapy. Since typical treatment doses range up to 20 Gy, calibrations that do not account for this effect can incur a large dosimetry error. The effect is dose rate dependent, but energy independent. For a dose rate of 900 cGy min(-1), the error in dose calibration varies between 2 and 3% for an average of 2.5%. At dose rates of 600 and 300 cGy min(-1), the error was 1.7% and 0.8% respectively. The average timer error at 900 cGy min(-1) was found to be 1.2 +/- 0.1 monitor units. It is argued that even a small timer error has serious dosimetry consequences for the implementation of intensity modulated radiation therapy.

Calibration↗
PubMed1998

Evidence for photoneutron production in the lead shielding of a dedicated intra-operative electron only facility.

A dedicated electron-only intra-operative suite has just been completed at the Massachusetts General Hospital. This suite is located on the 3rd floor with the shielding consisting entirely of lead and borated polyethylene, except for concrete in the floor and ceiling to support the lead and on the finished floor. The radiation protection barriers for this facility were calculated on the basis of a maximum permissible dose of 10 microSv wk(-1) for photons and 10 microSv wk(-1) for neutrons, based on a quality factor of 10 (this factor is specified in the regulations of the Commonwealth of Massachusetts). This even split was predicated on the basis that, except for the primary beam, the neutron leakage from the machine was generally about the same as for x rays. The initial survey showed that the neutron dose equivalent outside all barriers, except below the floor, was within the calculated values, < 10 microSv wk(-1). However, the neutron dose equivalent measured directly below the floor was found to be 35 microSv wk(-1) for the highest electron energy, a difference of > 25 microSv wk(-1). The neutron dose equivalent, for neutrons produced by bremsstrahlung photon interactions in the lead and based on a 3% photon background in the electron beam, was calculated to be 25 microSv wk(-1), in good agreement with this difference.

Electrons↗
PubMed1998

Two-dimensional dose distribution of a miniature x-ray device for stereotactic radiosurgery.

The Photon Radiosurgery System is a miniature x-ray device developed for the treatment of small intracranial neoplasms. The x-rays are generated at the tip of a 10-cm-long, 3-mm-diam probe with a nearly isotropic distribution. Results from measurements of the two-dimensional dose distribution around the x-ray source are presented using two methods: (1) dose measurement with an ionization chamber and a water phantom system and (2) dose measurement with radiochromic film and a solid water phantom. The shape of the two angular dose distributions in the axial plane agree with each other to with approximately 10% and the dose at 10 mm from the source, orthogonal to the probe axis, was about 20% lower than at the same distance along the axis. The relative dose difference of 20% corresponds to a change in distance from the source of +/- 0.3 mm at 10 mm. It is shown that the anisotropy of radiation distribution in the axial plane can be improved to approximately 10% by adjusting the electron beam with a 12% reduction in the overall radiation output.

Calibration↗
PubMed1998

Evidence for a significantly higher than expected depth dependence of wedge transmission factors on the 4 MV beam of a new dual energy accelerator.

Wedge transmission factors have been measured for two sets of physical wedges for the 4 MV beam of a new dual energy linear accelerator as a function of field size and depth. The field size dependence of these factors has been compared with the 4 MV beam from another, single-energy linear accelerator and a difference of a factor of approximately 2 has been observed in the relative wedge transmission factors between the two machines.

Monte Carlo Method↗
PubMed1997

Initial characterization of the dosimetry and radiology of a device for administering interstitial stereotactic radiosurgery.

OBJECTIVE: We report the design and initial characterization of the dosimetry and radiobiology of a novel device for interstitial stereotactic radiosurgery. INSTRUMENTATION: The device is lightweight, handheld, and battery-powered, and it emits x-ray radiation from the tip of a probe 3 mm in diameter by 10 cm in length. METHODS: The dosimetry was characterized by two independent methods: thermoluminescent dosimeters and radiochromic film. The radiobiology was characterized by in vivo irradiation of rat liver, dog liver, and dog brain. The animals were killed at varying intervals of time, and histological examinations were performed. Heat transfer from the probe to dog brain was studied in vivo by placing thermocouple sensors around the probe tip before irradiating. RESULTS: Both dosimetric methods showed a steep dose-distance fall-off relationship (proportional to the reciprocal of the cube of the distance from the probe tip). Rats and dogs that were killed weeks to months after liver irradiation tended to have sharply demarcated lesions. Liver enzyme levels, measured serially in the dogs, did not give evidence of chronic inflammation. Histological examination of the brains of dogs that were killed acutely after irradiation did not show evidence of inflammation, edema, or hemorrhage. The tissue temperature elevation 1 cm from the tip never exceeded 0.5 degree C, thereby excluding hyperthermia as a significant contributor to the formation of lesions. CONCLUSIONS: Because this device requires relatively few supporting resources, has sharp dosimetric properties, and seems to be safe, it may be useful as a clinical tool for interstitial stereotactic radiosurgery.

Animals↗
PubMed1996

The cylindromatosis gene (cyld1) on chromosome 16q may be the only tumour suppressor gene involved in the development of cylindromas.

Hereditary cylindromatosis is a rare autosomal dominant disease characterised by the development of multiple benign neoplasms of the skin. We recently localised the gene responsible for this disease (cyld1) to chromosome 16q12-q13 and provided evidence that it is a tumour suppressor gene (Biggs et al., 1995). We have now examined polymorphic markers on every chromosome, some of which are close to known tumour suppressor genes, in 25 tumours from 4 individuals with familial cylindromatosis. No loss of heterozygosity (LOH) was detected other than at loci on chromosome 16q. This observation suggests that the cyld1 gene may be the only tumour suppressor gene implicated in the development of cylindromas. We have also demonstrated LOH using markers on chromosome 16q in 8/14 (57%) sporadic cylindromas, indicating that the cyld1 gene is likely to be involved in the genesis of both familial and sporadic cylindromas.

Carcinoma, Adenoid Cystic↗
PubMed1996

Aspergillosis of the sphenoid sinus: presentation as a pituitary mass and postoperative gallium-67 imaging.

Invasive aspergillosis of the paranasal sinuses is an uncommon, but well-recognized, form of fungal infection. We describe an elderly female patient with invasive aspergillosis of the sphenoid sinus and associated osteomyelitis of the skull base, with clinical presentation as a pituitary mass. Postoperative gallium scan showed intense uptake in the sphenoid sinus, which resolved after treatment with amphotericin-B. This case demonstrates some of the pathologic and clinical features of invasive aspergillosis and suggests a potential role for gallium-67 imagining in monitoring clinical response to therapy.

Aged↗
PubMed1996

Soft tissue oncocytoma.

We describe a case of a novel soft tissue neoplasm, composed of a monotonous population of cells. Their cytoplasm was parked with mitochondria, and had no immunohistochemical or ultrastructural evidence of differentiation. The neoplasm, located within the thigh of a 50-year old man, was well-circumscribed but unencapsulated. The patient was clinically free of neoplasm at 1 year follow-up, after complete local excision. We propose the term "soft tissue oncocytoma" for this lesion, because of the similarity of this neoplasm to oncocytomas of other reported sites.

Adenoma, Oxyphilic↗