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A Ralston

Publications and source records attributed to A Ralston.

At least 19 recordsLinked to original sources
PubMed2005

Clinical application of the OneDose Patient Dosimetry System for total body irradiation.

The OneDose Patient Dosimetry System (Sicel Technologies) is a new dosimeter based on metal oxide semiconductor field-effect transistor technology and designed for the in vivo measurement of patient dose during radiotherapy. In vivo dosimetry for total body irradiation (TBI) is challenging due to the extended treatment distance, low dose rates and beam spoilers. Phantom results confirm the suitability of the dosimeter for TBI in terms of inherent build-up, post-irradiation fading, accuracy, reproducibility, linearity and temperature dependence. Directional dependence is significant and should be taken into account. The OneDose dosimeters were also trialed in vivo for two TBI patients and the dose measured compared to conventional dosimeter measurements using an ionization chamber and thermoluminescent dosimeters (TLD), with agreement to within 2.2% and 3.9%, respectively. Phantom and patient results confirm that the OneDose patient dosimetry system is a practical and convenient alternative to TLDs for TBI in vivo dosimetry. For increased confidence in results with this dosimeter, we recommend that two dosimeters be used for each site of interest.

Humans↗
PubMed2005

Genetic regulation of stem cell origins in the mouse embryo.

'Stem cell' has practically become a household term, but what is a stem cell and where does it come from? Insight into these questions has come from the early mouse embryo, or blastocyst, from which three kinds of stem cells have been derived: embryonic stem (ES) cells, trophoblast stem (TS) cells, and extraembryonic endoderm (XEN) cells. These stem cells appear to derive from three distinct tissue lineages within the blastocyst: the epiblast, the trophectoderm, and the extraembryonic endoderm. Understanding how these lineages arise during development will illuminate efforts to understand the establishment and maintenance of the stem cell state and the mechanisms that restrict stem cell potency. Genetic analysis has enabled the identification of several genes important for lineage decisions in the mouse blastocyst. Among these, Oct4, Nanog, Cdx2, and Gata6 encode transcription factors required for the three lineages of the blastocyst and for the maintenance their respective stem cell types. Interestingly, genetic manipulation of several of these factors can cause lineage switching among these stem cells, suggesting that knowledge of key lineage-determining genes could help control differentiation of stem cells more generally. Pluripotent stem cells have also been isolated from the human blastocyst, but the relationship between these cells and stem cells of the mouse blastocyst remains to be explored. This review describes the genetic regulation of lineage allocation during blastocyst formation and discusses similarities and differences between mouse and human ES cells.

Animals↗
PubMed2001

Extracorporeal irradiation for malignant bone tumors.

PURPOSE: Extracorporeal irradiation (ECI) has been used selectively in the management of primary malignant bone tumors since 1996. We report our techniques for ECI and the short-term oncologic and orthopedic outcomes. METHODS AND MATERIALS: Sixteen patients with primary malignant bone tumors were treated with ECI from 1996 to 2000. The median age was 14 years. The histologic diagnoses were Ewing's sarcoma (11), osteosarcoma (4) and chondrosarcoma (1). The treated sites were femur (7), tibia (4), humerus (2), ilium (2), and sacrum (1). Following induction chemotherapy in Ewing's sarcomas and osteosarcoma, en bloc resection of the tumor and tumor-bearing bone was performed. A single dose of 50 Gy was delivered to the bone extracorporeally using either a linear accelerator (9 cases) or a blood product irradiator (7 cases). The orthopedic outcome was recorded using a standard functional scale. RESULTS: At a median follow-up of 19.5 months, there were no cases of local recurrence or graft failure. One patient required amputation due to chronic osteomyelitis. For the 10 patients with follow-up greater than 18 months, the functional outcomes were graded good to excellent. CONCLUSION: The short-term oncologic and orthopedic results are encouraging and suggest that ECI provides a good alternative for reconstruction in limb conservative surgery in selected patients. This technique should only be used in a multidisciplinary setting, where careful follow-up is available to assess the long-term outcomes.

Adolescent↗
PubMed2001

Extracorporeal irradiation--novel use of a blood product irradiator.

A Cs-137 blood product irradiator (BPI) is used for extracorporeal irradiation of bone grafts. For dose verification purposes two bone phantoms were constructed of plaster of Paris and irradiated in the BPI. The first was a hollow cylinder measuring 15 cm x 3.3 cm to simulate cortical bone, filled with paraffin wax to simulate yellow bone marrow. The second was a concave ellipse 11.5 cm x 9.5 cm x 2.5 cm to simulate a section of ilium. The absorbed dose was measured with radiochromic film in the phantoms and in water for comparison with the manufacturer's calibration certificate. The relative dose distribution in the bone phantoms was measured using Li-F thermoluminescent dosimeters and normalized to a reference point near the centre of each phantom. The doses measured in water matched the calibration certificate within 4%. The doses measured at the cylindrical and elliptical phantom reference points were 49.9 Gy and 52.3 Gy respectively, compared to the nominal dose of 50.0 Gy. The relative doses within the cylindrical phantom ranged from 88% to 100% along the central axis of the wax cylinder, from 89% to 100% along the plaster/wax interface, and from 90% to 103% along the outer surface of the plaster cylinder. The relative doses within the elliptical phantom ranged from 100% to 108% along the inside surface, from 99% to 107% along the outer surface, and from 98% to 103% through the centre of the plaster ellipse. These data agree well with the isodose plot provided by the manufacturer.

Blood↗
PubMed2000

Crossveinless 2 contains cysteine-rich domains and is required for high levels of BMP-like activity during the formation of the cross veins in Drosophila.

The BMP-like signaling mediated by the ligands Dpp and Gbb is required to reinforce the development of most veins in the Drosophila wing. However, the formation of the cross veins is especially sensitive to reductions in BMP-like signaling. We show here that the formation of the definitive cross veins occurs after the initial specification of the longitudinal veins in a process that requires localized BMP-like activity. Since Dpp and Gbb levels are not detectably higher in the early phases of cross vein development, other factors apparently account for this localized activity. Our evidence suggests that the product of the crossveinless 2 gene is a novel member of the BMP-like signaling pathway required to potentiate Gbb of Dpp signaling in the cross veins. crossveinless 2 is expressed at higher levels in the developing cross veins and is necessary for local BMP-like activity. The Crossveinless 2 protein contains a putative signal or transmembrane sequence, and a partial Von Willebrand Factor D domain similar to those known to regulate the formation of intramolecular and intermolecular bonds. It also contains five cysteine-rich domains, similar to the cysteine-rich domains found in Chordin, Short Gastrulation and Procollagen that are known to bind BMP-like ligands. These features strongly suggest that Crossveinless 2 acts extracelluarly or in the secretory pathway to directly potentiate Dpp or Gbb signaling.

Alleles↗
PubMed1999

Cochlear implants: response to therapeutic irradiation.

PURPOSE: To determine the response of cochlear implants ("bionic ears") to therapeutic irradiation. METHODS AND MATERIALS: A patient with a cochlear implant was referred for palliative cranial irradiation. As there were no published or manufacturer's data available regarding the response to radiation, implants were tested for functional changes following irradiation. Cochlear implants were supplied by Cochlear Ltd. Two units each of models CI22M, CI22M (with the second generation integrated circuit) and CI24M were irradiated with 4 MV X-rays, and an unirradiated unit of each model was used as a control. The implants were irradiated initially with 25 daily fractions to 50 Gy. To determine the response at higher doses, 10 Gy fractions were delivered to the same implants to 100 Gy, followed by a final fraction of 50 Gy (total dose 150 Gy). The implants were tested after each 10 Gy, up to 1100 Gy, and at 150 Gy. Several indicators of functionality were assessed, including RF (radio frequency) link range, and stimulator output current. The radiation shielding effect of the implants was also assessed. RESULTS: Within the dose range < or = 50 Gy, the stimulator output current of the CI22M units was the only parameter to change. At higher doses (to 150 Gy), changes in current output continued, and gradual loss of RF link range occurred in the CI22M units. The CI24M units showed changes in output current to 100 Gy, and large changes at 150 Gy. Dose attenuation by the implants was measured at 6% for ipsilateral single field 4 MV X-rays. CONCLUSION: Our results suggest that patients with these cochlear implants can receive cranial irradiation with a low risk of implant failure. Changes in stimulator output current can be compensated simply by reprogramming the speech map after the course of radiation treatment.

Adenocarcinoma↗
PubMed1998

Thyroid dose in children undergoing prophylactic cranial irradiation.

PURPOSE: To determine the radiation dose received by the thyroid gland as a result of prophylactic cranial irradiation (PCI) in childhood leukemia and the factors influencing that dose. METHODS AND MATERIALS: The dose to the thyroid resulting from simulated cranial irradiation with parallel opposed lateral fields of an adult anthropomorphic (ART) phantom with both 6 MV X-rays and Cobalt-60 gamma-rays was measured using thermoluminescent dosimeters (TLDs). The dependence of thyroid dose on the distance of the field from the thyroid and the proportions of thyroid dose from stray radiation (leakage, scatter from jaws, etc.) and tissue scattered radiation were measured. The effects of a shadow tray and shielding blocks were also determined. Calculation of thyroid dose using the Clarkson scatter integration method was performed for 6 MV X-rays to compare with the measured doses. In vivo thyroid dose estimates were made using TLD measurements for three children receiving PCI with 6 MV X-rays. RESULTS: Using open, unshielded fields, the thyroid region of the phantom received 1.2-1.4% of the prescribed cranial dose for 6 MV X-rays and 1.5-1.7% for Cobalt-60. For both treatment units, stray radiation accounted for approximately two thirds of the thyroid dose and tissue scatter accounted for the remaining one third. The thyroid dose increased as the field moved closer to the thyroid, with an increasing proportion of the dose due to tissue scatter. Placement of a thyroid shielding block on a shadow tray reduced the thyroid dose by only 20% compared with the open, unshielded setup. Thyroid dose from 6 MV using open fields was affected by the orientation of the collimator. When the inferior field edge was defined by the lower jaw, the dose was reduced by 27% compared with the upper jaw. Good correlation of dose to the thyroid region was obtained between phantom measured doses, in vivo measured doses and calculation of dose using the Clarkson method. CONCLUSION: For PCI doses of 1800 or 2400 cGy in the adult phantom, the dose to the thyroid was 20-40 cGy (1-2%). For small children this could rise to approximately 5% of the prescribed dose, of which half was due to stray radiation. As the thyroid in children is very sensitive to radiation and the dose-response curve for thyroid tumor induction is linear, attempts to shield the thyroid during cranial irradiation are mandatory. Cobalt-60 units should not be used, as the thyroid dose was higher than using 6 MV X-rays. Collimator orientation and the use of shadow trays and shielding were important factors in determining thyroid dose.

Adult↗
PubMed1998

New methods for inactivation of lipid-enveloped and non-enveloped viruses.

Two new methods are described for inactivating lipid-enveloped and non-enveloped viruses in plasma-derived products such as coagulation factors and intravenous immunoglobulin (IGIV). Iodine/Sephadex delivers iodine to IGIV solutions in a slow, controlled way and allows for inactivation of > or = 4 logs of porcine parvovirus (PPV), a hardy non-enveloped virus, under conditions which do not measurably damage the structural or functional properties of the IGIV, and with essentially no iodination of the protein. All detectable enveloped and non-enveloped viruses were inactivated by this treatment. Gamma irradiation has been successfully used to inactivate viruses at the final vial stage in freeze-dried plasma proteins. Four logs of PPV were inactivated by irradiation in the presence of fibrinogen, factor VIII and alpha 1-proteinase inhibitor (API) at doses of 23, 28 and 30 kiloGray (kGy) respectively, while retaining 93% of fibrinogen solubility, 67% of factor VIII activity and over 80% of API activity. Bovine viral diarrhea virus (BVDV), a lipid-enveloped model for hepatitis C virus, was completely inactivated by radiation doses of 20-30 kGy in these products. Gamma irradiation was less effective in inactivating viruses in freeze-dried IGIV.

Animals↗
PubMed1997

Smoothened-mediated Hedgehog signalling is required for the maintenance of the anterior-posterior lineage restriction in the developing wing of Drosophila.

It is thought that the posterior expression of the 'selector' genes engrailed and invected control the subdivision of the growing wing imaginal disc of Drosophila into anterior and posterior lineage compartments. At present, the cellular mechanisms by which separate lineage compartments are maintained are not known. Most models have assumed that the presence or absence of selector gene expression autonomously drives the expression of compartment-specific adhesion or recognition molecules that inhibit intermixing between compartments. However, our present understanding of Hedgehog signalling from posterior to anterior cells raises some interesting alternative models based on a cell's response to signalling. We show here that anterior cells that lack smoothened, and thus the ability to receive the Hedgehog signal, no longer obey a lineage restriction in the normal position of the anterior-posterior boundary. Rather these clones extend into anatomically posterior territory, without any changes in engrailed/invected gene expression. We have also examined clones lacking both en and inv; these too show complex behaviors near the normal site of the compartment boundary, and do not always cross entirely into anatomically anterior territory. Our results suggest that compartmentalization is a complex process involving intercompartmental signalling; models based on changes in affinity or growth will be discussed.

Animals↗
PubMed1994

Glycol methacrylate embedding and microwave staining for light microscopy of the mouse cochlea.

This study examined the utility of a methacrylate-based embedding medium and microwave staining for light microscopic quantification of hair cells and spiral ganglion cells in the mouse cochlea. The most important phase of the preparation process involved slowing down the polymerization process. The tissue molecules so locked within the plastic matrix produced excellent preservation of the organ of Corti and adjacent structures including the spiral ganglion, as well as tissue ionic charges. Excitable by microwaves, these ionic charges accelerated the movement of the basic dye (hematoxylin) into the tissue, reducing the time for this segment of the staining process from approximately 45 minutes to 1-2 minutes. When embedded in glycol methacrylate (GMA), acidic dyes show less stain-cell affinity so that staining intensity and time cannot be improved significantly. However, addition of color extenders to the counterstain eosin produced distinguished staining of all tissue constituents. Thus, a combination of GMA embedding medium, use of the microwave for staining and addition of color extenders to the counterstain generated excellent structural resolution and contrast. This made both hair cell and spiral ganglion cell counts possible from within the same specimen and provided an opportunity for qualitative evaluation as well.

Animals↗
PubMed1994

Calibration of a cadmium IVNAA system.

An in vivo neutron activation analysis (IVNAA) system for the measurement of cadmium in the human liver and kidney was calibrated using cadmium doped liver and kidney phantoms in a water tank. The effect on the number of cadmium gammas detected with changes in organ position and cross-organ interference was assessed. The lower limits of detection were found to be 12 mg cadmium in the kidney and 7 ppm cadmium in the liver. This system was compared to five others using a performance index which considers equipment specifications and dose to the subject, and was found to rank second best for the liver measurements and second worst for the kidney measurements. The results from the organ position studies showed that the depth of the organs in the body has a great effect on the results, and differences between systems could be partially due to differences in calibration geometry.

Cadmium↗
PubMed1990

A study of impaired fibrin polymerization in patients with the nephrotic syndrome.

Clotting studies have been performed on 64 consecutive patients with nephrotic syndrome. The thrombin time was prolonged in 59. Fibrin polymerization was studied in 42 of the 59 patients with a prolonged thrombin time and an abnormality was present in 22. There was a significant correlation between the prolongation of the thrombin time and impairment of polymerization (p = 0.018). No correlation was found between these two parameters and the patient's sex, age and drug therapy. Furthermore there was no correlation with the prothrombin time, APTT, fibrinogen, FDP, antithrombin III and platelet counts. There was however a significant negative correlation between the thrombin time and the serum albumin level (p less than 0.05). No abnormal bleeding was observed during or after renal biopsy in these patients. Renal biopsy may be performed safely despite the grossly prolonged thrombin time and abnormal fibrin polymerization in patients with the nephrotic syndrome.

Adult↗
PubMed1988

Semi-automated analysis of manually reconstructed tracks of progressively motile human spermatozoa.

Several alternative algorithms for computer-assisted derivation of measurements of movement characteristics from manually reconstructed tracks of progressively motile human spermatozoa were compared. Fifty tracks were reconstructed at 30 Hz from video recordings and analysed using traditional manual methods and by four combinations of computer algorithms. The best algorithm set was identified ('Videomot.mdpt') and the values for the curvilinear, average path and linear velocities (VCVL, VAVE and VLIN respectively), the amplitude of lateral displacement of the sperm head about the axis of progression (AH) and the number of times the sperm head crossed the average path (the 'beat/cross frequency', BXF) obtained using it were compared to those obtained by manual analysis. There was a considerable time saving when the computer-assisted method was used and the values it gave for the various movement characteristics showed good correspondence with those obtained manually. In addition, repeated data entry and analysis was found to be highly reproducible. When the tracks were re-plotted at 6 Hz (as used by the multiple-exposure photomicrography method for sperm motility analysis) insufficient information remained in the tracks for reliable determination of anything other than VLIN. We conclude that the Videomot.mdpt program provides reliable values for the movement characteristics of progressively motile human spermatozoa, and believe it will be of great value in the validation of commercial systems providing automated sperm movement analysis and in laboratories which do not have access to such costly equipment.

Algorithms↗