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Biomedical subjects

J Beatty

Publications and source records attributed to J Beatty.

At least 19 recordsLinked to original sources

Analysis of transcriptional activity mediated by Drosophila melanogaster ecdysone receptor isoforms in a heterologous cell culture system.

Ecdysteroid regulation of gene transcription in Drosophila melanogaster and other insects is mediated by a heterodimer comprised of Ultraspiracle (USP) and one of three ecdysone receptor (EcR) isoforms (A, B1 and B2). This study revealed that the EcR/USP heterodimer displays isoform-specific capabilities. EcRB1 is normally induced with a form of USP that is missing its DNA-binding domain (DBD), although potentiation by juvenile hormone (JH) III is reduced. The EcRA and B2 isoforms, however, display almost no response to ecdysteroids with the DBD(-) USP. A mutation, K497E, in the shared ligand-binding domain of the EcR isoforms caused elevated EcRB2-specific affinity for a canonical ecdysone response element. The effects of directed modification and mutagenesis offer a strategy for developing hypotheses and considerations for studying in vivo function.

Animals↗

Hepatocellular carcinoma with secondary abscessation in a cat.

A 16-year-old castrated male domestic shorthair cat was presented for investigation of weight loss, lethargy, inappetence and polydypsia. On serum biochemical analysis there was evidence of severe hepatocellular damage and cholestasis. Abdominal ultrasonographic examination revealed an irregular lesion of mixed echogenicity in a left hepatic lobe. It was compromised of a hypoechoic periphery surrounding an anechoic central area containing highly echogenic densities with distal acoustic shadowing suggestive of gas formation. On necropsy, the only gross abnormality was a solitary 5 cm x 3 cm x 3 cm multilobulated mass in the left lateral hepatic lobe, containing foul-smelling purulent fluid within a thick fibrous wall. Cytological examination of the fluid revealed numerous degenerate neutrophils and large numbers of Gram-positive spore-forming rods. The histopathological diagnosis was hepatocellular carcinoma with secondary abscessation. The bacterial morphology was consistent with Clostridia sp. Both hepatocellular carcinoma and focal hepatic abscessation are rare in cats. Hepatic abscesses should be included in the differential diagnosis of cats with non-specific signs, even in the absence of biochemical evidence of a hepatopathy.

Animals↗

Acute superficial venous thrombophlebitis: does emergency surgery have a role?

BACKGROUND: Superficial venous thrombophlebitis (SVT) of the long saphenous vein (LSV) has been shown to be associated with thrombus propagation into the common femoral vein in up to 44% of cases. Conservative management can thus result in deep vein thrombosis (DVT), deep vein insufficiency or fatal pulmonary embolism (PE). To examine the effects of emergency division of the sapheno-femoral junction (SFJ) on the deep venous system in SVT of the LSV we used pre- and postoperative venous duplex ultrasound. METHODS: Emergency division of the SFJ was performed in 17 patients presenting with acute superficial venous thrombophlebitis. All patients had duplex ultrasound, which demonstrated thrombus of the above knee long saphenous vein together with a normal deep venous system. A follow-up duplex ultrasound scan was arranged on discharge and at 2 months. RESULTS: No patient had propagation of thrombus into the deep venous system or a PE. One patient developed a non-occlusive clot in the popliteal vein at 2 months follow-up. All patients were discharged at 48 hours. CONCLUSIONS: Using duplex ultrasound it has been shown that emergency division of the SFJ is a safe and effective way of preventing serious complications caused by thrombus in above knee LSV SVT.

Acute Disease↗

Scatter and attenuation measurements at distances greater than 10 cm from an 192Ir source.

Most algorithms developed by various investigators for use in brachytherapy treatment planning have typically been designed to calculate the dose within a 10 cm range of a radiation source. These algorithms predict the dose well at distances < 10 cm from the source but were not developed and should not be utilized to predict the dose at distances > 10 cm. On the contrary, treatment planning systems and manual calculations will produce erroneous results when dose points > 10 cm are calculated using these algorithms. The spread in the data generated by the above algorithms is 16% at 15 cm and 42% at 20 cm. Physical measurements were performed at distances between 5 and 50 cm from a high activity 192Ir source in water. The measured data correlated well with the predicted data from 5 to 10 cm, which had a 5% spread. Beyond 10 cm the measured data fell central to the range of the predicted data, with the spread of the predicted data increasing from 5% to 80% with increasing distance from the source. The measured data was fitted with a model incorporating a buildup factor and an attenuation factor. The best fit values are in reasonable agreement with those obtained by two of the investigators, Thomason and Tripathi.

Algorithms↗

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↗

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↗

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↗

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↗

Dosimetric results from a feasibility study of a novel radiosurgical source for irradiation of intracranial metastases.

PURPOSE: A feasibility study addressing the role of a new miniature x-ray device, the Photon Radiosurgery System (PRS), for interstitial radiosurgical treatment of intracranial metastatic neoplasms, was conducted at our institution. To gain insight into the role of PRS vis-à-vis other currently available radiosurgical treatment modalities, dosimetric comparisons of Linac Radiosurgery and proton beam therapy were performed in the treatment of a small approximately spherical metastasis. METHODS AND MATERIALS: The photon radiosurgery system is a miniature, battery operated, high-voltage x-ray generator that produces low-energy x-rays with an effective energy of 10-20 keV emanating from the tip of a probe stereotactically inserted into small tumors (< 3 cm in diameter) in humans. Patients, 18 years or older, with supratentorial mass lesions less than 3 cm in diameter were eligible if they were likely to survive their systemic cancer and be capable of self-care for more than 4 months. Patients were ineligible if presenting with infratentorial lesions, contraindications for biopsy, or receipt of chemotherapy or radiotherapy within 4 weeks were ineligible. RESULTS: Fourteen patients with metastatic supratentorial lesions were treated from December 1992 to December 1993 for metastatic tumors to the brain. Single doses of 10-20 Gy were delivered to spherical targets of 10 to 35 mm in diameter. Treatment, including biopsy, pathologic review and radiation treatment, generally took less than 3 h. One patient, later found to have an ischemic stroke, developed a small hemorrhage from the biopsy that preceded interstitial irradiation. There were no other complications. Median survival was 10 months. Three locally recurrent lesions failed at 3.5, 4, and 10 months after treatment. All patients had stable or improved Karnofsky status for 2 weeks to 21 months after treatment. The PRS dosimetry appears at least as good as that obtained using 6 MV Linac or 160 MeV protons. Analyses of dose-volume histograms comparing the volumes of normal CNS tissue irradiated employing each of the respective modalities suggest a small sparing of normal tissue with PRS, as opposed to linac or protons, in this patient population with small, approximately spherical tumors. CONCLUSIONS: The PRS device provides a unique cost and time efficient procedure for providing interstitial radiation therapy immediately following histologic confirmation of malignancy in patients undergoing biopsy of intracranial lesions. The PRS treatment appears safe, and preliminary data suggest no evidence of treatment-related morbidity within the life span of the selected patient population. When treating small, spherical lesions, PRS appears to offer a modest dosimetric advantage over Linac or proton beam therapy in sparing normal tissue. These encouraging results have prompted a Phase II trial that is currently underway. Further efforts are necessary in the design of a clinically relevant trial addressing the role of fractionated external beam radiation therapy with boost vs. PRS treatment with WBRT in the treatment of single metastases.

Adult↗

A new miniature x-ray device for interstitial radiosurgery: dosimetry.

A miniature, battery operated 40 kV x-ray device has been developed for the interstitial treatment of small tumors ( < 3 cm diam) in humans. X rays are emitted from the tip of a 10 cm long, 3 mm diameter probe that is stereotactically inserted into the tumor. The beam, characterized by half-value layer (HVL), spectrum analysis, and isodose contours, behaves essentially as a point isotropic source with an effective energy of 20 keV at a depth of 10 mm in water. The absolute output from the device was measured using a parallel plate ionization chamber, modified with a platinum aperture. The dose rate in water determined from these chamber measurements was found to be nominally 150 cGy/min at a distance of 10 mm for a beam current of 40 microA and voltage of 40 kV. The dose in water falls off approximately as the third power of the distance. To date, 14 patients have been treated with this device in a phase I clinical trial.

Biophysical Phenomena↗