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Biomedical subjects

E L Gillette

Publications and source records attributed to E L Gillette.

At least 19 recordsLinked to original sources
PubMed1998

Volume effects in the irradiated canine spinal cord: do they exist when the probability of injury is low?

PURPOSE: The purpose of this study was to investigate volume effects in the irradiated canine spinal cord. MATERIALS AND METHODS: Eighty-nine beagle dogs were given 44-84 Gy photons in 4 Gy fractions to 4 or 20 cm lengths of thoracic spinal cord. As controls, 36 dogs were given 60-84 Gy in 2 Gy fractions to a 20 cm length of spinal cord and six dogs were unirradiated. Dogs were evaluated for clinical signs, and after euthanasia, for occurrence of gross lesions, severe lesions of massive hemorrhage, white matter necrosis and/or parenchymal atrophy and mild lesions of focal fiber loss. White matter vacuoles, meningeal thickness and dorsal root ganglia lesions were quantified. Data were analyzed to test for an effect of volume on dose-response curves. RESULTS: Significant volume effects were found between 4 and 20 cm lengths of irradiated spinal cord for gross lesions, severe lesions and mild lesions (8.3-15.0 Gy difference at the ED50 level). The ED50 in 4 Gy fractions for severe lesions was 56.9 Gy (95% CI 53.1-60.6) for 20 cm and 68.8 Gy (95% CI 64.5-75.1) for 4 cm fields. Significant improvements in the fit of data to dose-response curves resulted when using models with either parallel or non-parallel curves, but in either case an appreciable difference existed between curves at low probabilities of injury. Volume effects were present for meningeal thickness and slopes of dose-response curves were different. Clinical signs correlated well with severe lesions for 20 cm (ED50 = 54.0 Gy), but not for 4 cm fields (ED50 = 77.6 Gy). CONCLUSIONS: Volume effects exist for the occurrence of pathologic lesions in irradiated canine spinal cord. Clinical compensation for pathologic lesions occur at small, but not large irradiated volumes. There is insufficient data to support a decreased slope of dose-response curves with decreased volume. Volume effects estimated at the 50% level of spinal cord injury could also hold at low probabilities of injury characteristic of the clinic.

Animals↗
PubMed1998

Response of the canine esophagus to irradiation.

One hundred twenty-eight beagle dogs were randomized to receive thoracic irradiation with doses between 0 and 72 Gy in 1.5-Gy fractions over 6 weeks. Dogs were randomized to have either 33, 67 or 100% of their lung volume irradiated. The entire thoracic portion of the esophagus and variable portions of the fundus of the stomach were included in the treatment field at all volumes. Sixteen of the 128 dogs entered in the study developed clinical signs of esophagitis. These 16 dogs received doses between 45 and 72 Gy. Clinical signs of esophagitis/gastritis included dysphagia, anorexia, emesis, excessive salivation and weight loss that required force-feeding of a liquid diet. An ED50 of 67.2 Gy (95% CI 61.45-79.7 Gy) was calculated for the occurrence of clinical signs that required some supportive treatment. Three of the 16 dogs receiving 63 or 72 Gy failed to respond to treatment and were euthanized. Twenty-five other dogs were euthanized prior to 2 years due to other treatment-related complications. Two dogs died of causes not related to treatment. No late esophageal complications were observed in the remaining 98 dogs out to 2 years after irradiation. Esophageal specimens from 79 dogs were available for quantitative histological analysis 2 years after irradiation. Histological analysis showed a decrease in the percentage of glandular tissue with a corresponding increase in lamina propria and muscle.

Animals↗
PubMed1998

Effects of volume irradiated on the function of the canine ureter.

This study was designed to investigate the influence of the volume irradiated on the probability of ureteral complications and to provide data for volume modeling. One hundred thirty-four purpose-bred beagle dogs received single intraoperative doses of 6 MeV electrons ranging from 12 to 54 Gy to three lengths of ureter: 2, 4 or 8 cm. The response was evaluated by excretory urography. The ED50 was 21.9 Gy (95% CI 13.3-30 Gy) for 8 cm 3 years after treatment. The estimated ED50's were greater than 43 Gy for 4 cm and 85 Gy for 2 cm. Reducing the length of ureter irradiated from 8 cm to 4 cm increased the ED50 for ureteral dilation by at least a factor of 2, while reduction from 8 cm to 2 cm increased the ED50 by at least a factor of 4. The ED50 for renal injury secondary to stenosis was 30.5 Gy (95% CI 17.2-232 Gy) when an 8-cm field was irradiated. There was a significant effect of volume irradiated on the frequency of ureteral stenosis. Reducing the length of ureter included in the treatment field should allow delivery of higher doses to tumors without increased complications.

Animals↗
PubMed1997

History of veterinary radiation oncology.

The history of veterinary radiation oncology is reviewed from 1895 to the present. The field was very slow to develop from the early 1900s to the 1980s. Rapid progress is now being made with much greater interest on the part of the companion animal-owning public for more advanced treatment of various diseases. The number of veterinary radiation oncologists and the number of well-equipped radiation therapy centers are increasing.

Animals↗
PubMed1997

Late response to whole-lung irradiation alone and with whole-body hyperthermia in dogs.

The late effects of whole-lung irradiation with and without whole-body hyperthermia were studied in beagle dogs. The reference doses ranged from 18 to 49.5 Gy given in 1.5-Gy fractions over 6 weeks. Whole-body hyperthermia was given in three 2-h treatments to a deep rectal temperature of 42.0 degrees C. Radiation was given simultaneously with hyperthermia on those days. Physiological and histopathological responses were evaluated. Physiological changes included decreases in cardiac output, systemic blood pressure, dynamic compliance and serotonin uptake. Early changes included an increase in extravascular water and total protein in the lavage. These changes were considered mild, were compensated for and occurred only in dogs receiving doses of 40.5 Gy or greater given in 1.5-Gy fractions over 6 weeks. Histopathological changes were typical of irradiated lung and included pleural fibrosis, interstitial fibrosis, fibrotic foci, and peribronchial and perivascular fibrosis. There was no enhancement of late injury to lung by hyperthermia seen in this study.

Animals↗
PubMed1996

Immunohistochemical evidence of rapid extracellular matrix remodeling after iron-particle irradiation of mouse mammary gland.

High-LET radiation has unique physical and biological properties compared to sparsely ionizing radiation. Recent studies demonstrate that sparsely ionizing radiation rapidly alters the pattern of extracellular matrix expression in several tissues, but little is known about the effect of heavy-ion radiation. This study investigates densely ionizing radiation-induced changes in extracellular matrix localization in the mammary glands of adult female BALB/c mice after whole-body irradiation with 0.8 Gy 600 MeV iron particles. The basement membrane and interstitial extracellular matrix proteins of the mammary gland stroma were mapped with respect to time postirradiation using immunofluorescence. Collagen III was induced in the adipose stroma within 1 day, continued to increase through day 9 and was resolved by day 14. Immunoreactive tenascin was induced in the epithelium by day 1, was evident at the epithelial-stromal interface by day 5-9 and persisted as a condensed layer beneath the basement membrane through day 14. These findings parallel similar changes induced by gamma irradiation but demonstrate different onset and chronicity. In contrast, the integrity of epithelial basement membrane, which was unaffected by sparsely ionizing radiation, was disrupted by iron-particle irradiation. Laminin immunoreactivity was mildly irregular at 1 h postirradiation and showed discontinuities and thickening from days 1 to 9. Continuity was restored by day 14. Thus high-LET radiation, like sparsely ionizing radiation, induces rapid-remodeling of the stromal extracellular matrix but also appears to alter the integrity of the epithelial basement membrane, which is an important regulator of epithelial cell proliferation and differentiation.

Animals↗
PubMed1995

Late radiation injury to muscle and peripheral nerves.

Late radiation injury to muscles and peripheral nerves is infrequently observed. However, the success of radiation oncology has led to longer patient survival, providing a greater opportunity for late effects to develop, increase in severity and, possibly, impact the quality of life of the patient. In addition, when radiation therapy is combined with surgery and/or chemotherapy, the risk of late complications is likely to increase. It is clear that the incidence of complications involving muscles and nerves increases with time following radiation. The influence of volume has yet to be determined; however, an increased volume is likely to increase the risk of injury to muscles and nerves. Experimental and clinical studies have indicated that the alpha/beta ratio for muscle is approximately 4 Gy and, possibly, 2 Gy for peripheral nerve, indicating the great influence of fractionation on response of these tissues. This is of concern for intraoperative radiation therapy, and for high dose rate brachytherapy. This review of clinical and experimental data discusses the response of muscle and nerves late after radiation therapy. A grading system has been proposed and endpoints suggested.

Humans↗
PubMed1995

Ultrastructural morphometric analysis of peripheral nerves after intraoperative irradiation.

Intraoperative irradiation (IORT) is used to enhance local tumour control by using large, single doses while removing critical structures from the treatment field. Peripheral nerve remains a dose-limiting normal tissue that often cannot be removed from the field. To assess ultrastructural changes in canine sciatic nerve after IORT, computerized morphometric analysis of plastic sections and electron micrographs of nerve cross-sections was used. Surgically exposed sciatic nerves were irradiated with 6 MeV electrons to 12, 20 or 28 Gy. Twelve months after treatment dogs were killed humanely and the nerves from three dogs per dose group, including non-irradiated controls, were analyzed. Twelve months after 28-Gy IORT a significant decrease in nerve fiber density occurred. Nerve fiber loss was particularly prominent in the central portion of the nerve predominantly among large nerve fibers. Other nerve fiber parameters including fiber and axon area, diameter and perimeter, myelin thickness, form factor (measure of roundness), and G ratio (axon diameter/fiber diameter) did not show significant, dose-related changes. An increase in microtubule and neurofilament density in irradiated nerve axons was found. These changes are suggestive of radiation-induced hypoxia (damage to microvasculature) resulting in axon damage and subsequent nerve fiber loss as a possible mechanism of late radiation injury to peripheral nerve.

Animals↗
PubMed1995

Principles of radiation therapy.

Radiation therapy can provide long-term control of local or locoregional cancer without removal of large volumes of tissue and with preservation of function of surrounding normal tissues. Radiation therapy is used for cancers that have extended near or around critical structures such as spinal cord, nerves, or large vessels. Normal tissue response limits the total radiation dose that can be used. The objective of radiation therapy is to provide the highest probability for local tumor control with a probability for serious complications such as bone or soft-tissue necrosis of less than 5%. Radiation therapy can be used in combination with surgery and/or chemotherapy; however, there should be a carefully coordinated treatment plan. The basic principle of cancer treatment with curative intent is to treat as early and as aggressively as possible. The first opportunity for tumor control is always the best opportunity. Radiation oncologists are using improved equipment and greater knowledge of radiation biology to maximize tumor control and to minimize normal tissue injury. Currently, most veterinary radiation oncology practices use an external beam source of radiation from either cobalt 60 teletherapy units or clinical accelerators. Many practices use daily treatments for 3 to 4 weeks. The relatively short overall treatment time prevents significant repopulation of tumor cells during the course of treatment. The total dose is divided into several smaller fractional doses that spares late responding normal tissues.

Animals↗
PubMed1995

Radiation therapy for head and neck cancers.

Radiation therapy may be indicated for larger invasive tumors of the head and neck that may be difficult to surgically excise or for which surgery would be significantly disfiguring. Previous studies of oral squamous cell carcinomas indicate that it should be possible to control approximately 80% of all but the most advanced local or locoregional tumors. Aggressive radiation therapy to total doses of 56 Gy or greater may be required. That can be done by using smaller doses per fraction and gradually reducing the size of the field so that the highest dose is given only to the tumor with a relatively tight margin. Malignant melanomas can be controlled locally apparently with a few large fractions. Metastatic disease limits survival; therefore, some type of systemic therapy seems to be needed to improve survival of those patients. Canine oral fibrosarcomas require a very high dose for a reasonable probability of control. It seems that a dose of 56 Gy given in 3.3 Gy fractions might provide local control of 50% of the tumors. It is likely that a combination of surgery and radiation would significantly improve the probability for control. Oral squamous cell carcinomas of cats must also be treated very aggressively to improve local control. Tumors of the nasal cavity are usually very large and invasive at the time of diagnosis. Radiation therapy has been shown to be effective in some instances. It is possible that with better definition of the tumor through computerized tomography imaging and improved treatment planning, control of these difficult to manage nasal tumors can be improved.

Animals↗
PubMed1995

Soft-tissue sarcomas.

Canine and feline soft-tissue sarcomas are difficult to control with surgery unless aggressive procedures such as compartmental resection or amputation are performed. Additionally, multiple noncurative surgeries result in recurrent tumors that are difficult to control with other modalities. Little is known about the radiation response of soft-tissue sarcomas in animals, but available data suggest they are radioresistant. Various methods of improving radiation response of soft-tissue sarcomas have been evaluated. These include the combination of radiation with radioprotective agents, hyperthermia, and surgery. Of all methods evaluated to date the judicious combination of surgery and radiation seems to hold the most promise for producing permanent local control of a significant percentage of canine and feline sarcomas.

Animals↗
PubMed1995

Normal tissue tolerance and management of radiation injury.

The objective of effective cancer therapy includes preservation of normal tissue function and reducing injury as much as possible. Acutely responding tissues such as skin and mucous membranes generally show a reaction during the course of radiation therapy. Normally those reactions heal rapidly after radiation therapy is completed. The short-term injury is justified if a reasonable probability of local tumor control is expected with an increase in survival of several months. Late effects are more challenging to manage and, therefore, the probability of occurrence is reduced by the methods of irradiation. If the tumor is located such that eyes or salivary glands are included in the field, the late effects include keratoconjunctivitis sicca and, less frequently, xerostomia. Those responses require continual observation and care by the animal owner. A goal in radiation therapy is to keep the incidence of serious complications such as bone or soft-tissue necrosis below 5%. The incidence of complications of radiation therapy that have serious impact on quality of life or quality as a companion animal is probably much less than 5%.

Animals↗
PubMed1994

Impact of heterogeneity in the predictive value of kinetic parameters in canine osteosarcoma.

Intratumoral heterogeneity has been identified as a potential problem in the efficacy of predictive assays. Canine osteosarcoma is an extremely heterogeneous solid tumor that has been shown to be an excellent model for the human disease. Intratumoral heterogeneity of kinetic parameters and the effect of heterogeneity on predicting outcome of treatment (time until metastasis) were studied in dogs with naturally occurring osteosarcoma. Dogs were treated with amputation or tumor excision and limb-sparing followed by chemotherapy with cisplatin. Kinetic parameters evaluated included v, duration of DNA synthesis (Ts), and potential doubling time (Tpot), determined using in vivo labeling with bromodeoxyuridine and flow cytometry. In 30 tumors, multiple samples were obtained and evaluated. There was significantly more variation between tumors from different dogs than intratumoral variation of v, Ts, and Tpo. Variations in v, Ts, and Tpot within a tumor were associated with both sample location and tumor subpopulation. Time to metastasis was determined in 51 dogs with tumors sampled for kinetics. Multiple samples were available from 25 of these tumors. Cox proportional hazard analysis was performed using either the fastest or slowest Tpot from each sample. The fastest available Tpots were highly significant (P < 0.001) for prediction of outcome. The slowest available Tpots were also significant predictors, although the statistical strength was compromised (P = 0.024). Obtaining at least two samples in large tumors known to be heterogeneous is recommended to improve the predictive ability of Tpot. v is a more limited predictor but can useful when Tpot is not available. In canine osteosarcoma, an extremely heterogeneous tumor, kinetic parameters were shown to be predictors of outcome.

Animals↗
PubMed1994

Intraoperative radiation (IORT) injury to sciatic nerve in a large animal model.

Peripheral nerve appears to be a dose-limiting normal tissue in the clinical application of intraoperative radiation therapy (IORT). To assess IORT injury to peripheral nerve, three groups of five beagle dogs received doses of 12, 20 or 28 Gy to the surgically exposed and isolated right sciatic nerve in the mid-femoral region using 6 MeV electrons. The left sciatic nerve of each dog served as its own control. As a surgical control five dogs received surgical exposure of the nerve only. Monthly neurologic exams, electromyogram and nerve conduction studies were performed following treatment for 12 months. After that dogs were euthanatized and histologic studies of nerves were done to define the degree of axon and myelin loss as well as presence of fibrosis and vascular lesions for different doses of IORT. Results showed that the threshold dose most likely related to expression of severe radiation damage to the nerve in this model is between 20 and 25 Gy. Radiation injury to peripheral nerve appears to be the result of direct radiation effects on Schwann cells and nerve vasculature and secondary effects resulting from damage to regional muscle and vasculature. A theoretical mechanism of radiation injury to peripheral nerve is proposed.

Animals↗
PubMed1994

Biological half-life of aerosolized 99mTc-diethylenetriaminepentaacetate in various lung regions of clinically normal beagles.

The biological half-life (TB) of aerosolized 99mTc-diethylenetriaminepentaacetate was determined in 14 lung regions of 18 clinically normal Beagles. Three groups of lung regions or volumes were identified on the basis of significantly (P < 0.05) different TB. Group A (mean +/- SD TB, 82 +/- 21 minutes) included the transversely oriented cranial and caudal nonperihilar regions. Group B (mean +/- SD, 61 +/- 15 minutes) represented all sagittally oriented lung regions and the entire lung field. Group C (mean +/- SD, 49 +/- 11 minutes) included the transversely oriented cranial and caudal perihilar regions. Clearance of 99mTc-diethylenetriaminepentaacetate is considered a function of transepithelial transport into the blood, as well as bronchial transport via the mucociliary transport mechanism.

Anesthesia, General↗
PubMed1992

Late radiation response of canine mediastinal tissues.

The mediastinal tissues which included heart, lung, trachea and esophagus of 70 adult beagle dogs were irradiated to a range of total radiation doses between 24 and 68 Gy given in 2, 3 and 4 Gy fractions. The purpose of the study was the calculation of alpha/beta ratios for morphologic and functional changes of the mediastinal tissues. Functional assays including echocardiography, electrocardiography, right heart hemodynamics and cardiac output were performed. Histomorphometric analyses of all tissues included in the field were done 2 years after treatment. Euthanasia was performed on 7 of 70 dogs prior to 2 years due to congestive heart failure and seven other dogs had signs of heart failure 2 years after treatment. Heart failure was thought to be caused by either pericardial effusions or constrictive pericarditis in these dogs. Heart failure occurred at doses of 62 and 68 Gy given in 2 Gy fractions, 60 Gy given in 3 Gy fractions and 52 Gy given in 4 Gy fractions. The ED50 values for pericardial fibrosis for 2, 3 and 4 Gy fractions were 46.1, 43.9 and 26.6 Gy, respectively. An alpha/beta ratio of 2.5 Gy was calculated by direct quantal response analysis. Small foci of myocytolytic lesions were detected in 11 dogs. Calculated ED50 values for myocytolysis were 70.4 Gy given in 2 Gy fractions and 50.8 Gy given in 4 Gy fractions. The estimated alpha/beta ratio was 3.2 Gy. Heart rates determined from physical examination and frequency of S-T segment changes increased with increasing dose. No other dose related changes were found in any of the other functional parameters. Functional changes were detected in the 14 dogs with clinical signs of heart failure. Focal consolidation and subpleural fibrosis were present in the irradiated lung volume. These late changes had no detectable physiologic effect in these dogs because of the small volume of lung irradiated. The ED50 values for lung consolidation were 54.3, 45.8 and 26.6 Gy after 2, 3 or 4 Gy fractions, respectively. The estimated alpha/beta ratio was 3.4 Gy. No dose-related changes could be detected in the trachea or esophagus at 2 years after treatment. These results demonstrate that lung and pericardium are the most responsive tissues in the mediastinum within the first 2 years after treatment. Myocardial lesions were present with high ED50 values, but were not found to be functionally significant at 2 years after irradiation. Human clinical data indicate that longer observation periods are needed for development of these lesions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Pathology of radiation injury to the canine spinal cord.

The histopathologic response of the canine spinal cord to fractionated doses of radiation was investigated. Forty-two dogs received 0, 44, 52, 60, or 68 Gy in 4 Gy fractions to the thoracic spinal cord. Dogs were evaluated for neurologic signs and were observed for 1 or 2 years after irradiation. Six major lesion types were observed; five in the irradiated spinal cord and one in irradiated dorsal root ganglia. The three most severe spinal cord lesions were white matter necrosis, massive hemorrhage, and segmental parenchymal atrophy which had an ED50 of 56.9 Gy (51.3-63.3 Gy 95% CI) in 4 Gy fractions. These lesions were consistently associated with abnormal neurologic signs. Radiation damage to the vasculature was the most likely cause of these three lesions. The two less severe spinal cord lesions were focal fiber loss, which had an ED50 of 49.5 Gy (44.8-53.6 Gy 95% CI) in 4 gy fractions and scattered white matter vacuolation that occurred at all doses. These less severe lesions were not consistently associated with neurologic signs and indicated the presence of residual damage that may occur after lower doses of radiation. Radiation damage to glial cells, axons, and/or vasculature were possible causes of these lesions. In the irradiated dorsal root ganglia, affected sensory neurons contained large intracytoplasmic vacuoles, and there was loss of neurons and satellite cells. Such alterations could affect sensory function. The dog is a good model for spinal cord irradiation studies as tolerance doses for lesions causing clinical signs are close to the estimated tolerance doses for humans, and studies involving volume and long-term observation can be done.

Animals↗