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Biomedical subjects

P R Gavin

Publications and source records attributed to P R Gavin.

At least 19 recordsLinked to original sources

Clinical signs associated with brain tumors in dogs: 97 cases (1992-1997).

OBJECTIVE: To determine the prevalence of various clinical signs in dogs with brain tumors. DESIGN: Retrospective study. ANIMALS: 97 dogs with brain tumors. PROCEDURE: Medical records were reviewed for signalment, tumor type and location, and clinical signs. RESULTS: 33 breeds were represented; Golden Retrievers were most commonly affected. Most dogs were older (median age, 9 years); 95% of dogs were > or = 5 years old. Seventy-six percent of dogs had tumors in the supratentorial region. Seizures were the most common clinical sign at initial examination, with lower prevalence for circling, ataxia, and head tilt. Meningioma was the most common tumor. CONCLUSIONS AND CLINICAL RELEVANCE: Brain tumors develop most often in dogs > or = 5 years old and are uncommon in dogs < 5 years old. Seizures are a common clinical sign, and a brain tumor should be considered in dogs that have their first seizure after they are 4 years old.

Age Factors

Intracranial neoplasia.

A diagnosis of intracranial neoplasia in companion animals may be made by computed tomography (CT) or magnetic resonance imaging (MRI). MRI is the better method for detecting and characterizing intracranial tumors because of its superior depiction of soft tissues and relative lack of degrading artifacts, intracranial tumors may be characterized by distinct features; a systematic evaluation of these features on CT or MRI images may help to identify specific tumor types. In this article, guidelines for formulating differential diagnoses based on these imaging criteria will be discussed. Technical recommendations and protocols for CT and MR imaging will also be provided.

Animals

Seizures as a complication of brain tumors in dogs.

Seizures are a common reflection of a variety of intracranial physiologic abnormalities in dogs. In dogs with brain tumors, seizures often provide the clinical clue to the existence of an underlying structural brain disease. The majority of brain tumors that result in seizures affect the supratentorial nervous system, especially the olfactory and frontal lobes. Diagnosis requires advanced imaging such as computed tomography (CT) or magnetic resonance imaging (MRI) to establish the presence of a structural abnormality. Therapy is directed both at tumor and seizure control to afford the best chance of successful management of dogs with brain tumors.

Animals

Future of veterinary radiation oncology.

Rapid developments in technology will have a profound effect on veterinary radiation oncology. These developments include computer-enhanced, three-dimensional treatment planning and smaller, more compact, more reliable radiation equipment, primarily linear accelerators. For treatment of all veterinary patients, the linear accelerators need electron capability. Although fractionated therapy will remain the standard from of treatment, new modalities, including a highly precise single-dose treatment called radiosurgery, and a precise fractionated therapy called conformal therapy, will be utilized more in the future.

Animals

A review: CNS effects and normal tissue tolerance in dogs.

Large animal studies have been utilized to define tolerance of normal brain to irradiation and verify treatment planning programs with two recently installed epithermal neutron beams. The normal brain tolerance studies utilized two biological endpoints, magnetic resonance visible damage only and neurologic signs progressing to death. The studies focused on defining the proton RBE for the contaminant fast neutrons, and from nitrogen capture of thermal neutrons and boron capture reaction biologic effect. The proton RBE was approximately 3.0 to 6.7, depending on whether a dose reduction factor for the low gamma dose rate was employed. The microscopic distribution of the boron compounds, coupled with the extremely short length of the fission fragments from thermal neutron capture by 10B yields an observed biologic effect much less than would be expected from such high LET irradiation. This observed biologic effect, which is a product of the microdistribution of the boron atom and the relative biologic effect of the fission fragments has been termed compound factor. The compound factor was based on the calculated physical dose from the fission fragment in blood based on measured blood 10B concentration. The approximate compound factor for BSH was studied at the two institutions and it ranged from 0.27 to 0.55, depending on the site and the endpoint chosen. The mean compound factor for BPA was only studied at one site and was found to be 1.1 for both endpoints. The increase in the compound factor for BPA is in keeping with previous calculations based on the differences in compound distribution. Results of these studies has helped the initiation of phase I and phase II clinical trials at Brook haven National Laboratory and the planned European clinical trials at Petten, The Netherlands.

Animals

Quantitative 123I IMP and 99mTc HMPAO imaging in the dog following cocaine administration.

SPECT and associated imaging procedures were used in beagle dogs to (1) evaluate the uptake, distribution, and clearance properties of i.v.-injected 123I IMP (IMP) and 99mTc HMPAO (HMPAO) in the brain, lungs, liver, and kidneys; (2) quantify the acute effects (after 15 sec) of very low doses (0.5 or 1.0 mg/kg) cocaine on the kinetics and localization properties of IMP and HMPAO; and (3) evaluate comparative imaging properties of IMP and HMPAO for measuring regional cerebral blood flow (rCBF). Regional and global uptake and localization of IMP or HMPAO were evaluated in control studies using dynamic planar (0-30 min) and SPECT imaging (at 35 min). The regional distribution properties of IMP and HMPAO in the brain were estimated from regions of interest (ROIs) drawn around anatomic structures on MR slices and manually registered with corresponding SPECT slices. Cocaine significantly reduced the 30-min IMP uptake in the brain and lungs by approximately 15%, but only slightly changed HMPAO uptake in the brain and other organs. In the control studies, the respective uptakes of IMP in the brain and lungs were 9 and 39% greater (p < 0.01) than those of HMPAO. In control SPECT studies, the highest uptake of IMP was observed in the thalamus and progressively less activity was observed in the parietal lobe, frontal lobe, cerebellum, occipital lobe, and entire brain; activity in the olfactory bulb was lower than in all other regions. Cocaine reduced IMP uptake in the cerebellum (p < 0.01), occipital lobe (p < 0.01), and entire brain (p < 0.05). IMP uptake (cpm/pixel-mCi) in the different brain regions was 1.3 to 2.1 times greater than that of HMPAO (p < 0.001). HMPAO uptake was more homogeneous throughout the gray matter of the brain; no significant uptake differences were observed among flagged regions. Results indicate that single, acute doses of cocaine, 0.5 and 1.0 mg/kg, significantly altered the uptake and localization properties of IMP in the dog's brain, lungs, liver, and kidneys. Variations in regional uptake of IMP in the parietal, frontal, and occipital lobes, cerebellum, and thalamus were greater than with HMPAO.

Amphetamines

Intracranial tumors.

Intracranial tumors in dogs are relatively common but are less common in cats. Features of various tumors are described. The antemortem diagnosis is based on demonstrating the mass with advanced imaging. Tumor type, however, can only be diagnosed by histological confirmation. Diagnosis and treatment options are discussed.

Animals

Effect of craniectomy/durotomy alone and in combination with hyperventilation, diuretics, and corticosteroids on intracranial pressure in clinically normal dogs.

OBJECTIVE: To determine the effect of craniectomy and durotomy on intracranial pressure (ICP) in clinically normal dogs. DESIGN: Two-part study (experiments A and B) involving craniectomy and durotomy, with and without treatments to lower ICP. ANIMALS: Six (experiment A) and 7 (experiment B) healthy dogs. PROCEDURE: In experiment A, craniectomy was performed in combination with durotomy, diuretic administration, methylprednisolone sodium succinate administration, and hyperventilation, and effect of these manipulations on ICP was determined. In experiment B, dogs had only craniectomy and durotomy without associated ICP-lowering treatments. During both experiments, ICP was monitored throughout the surgical procedure with a fiber optic ICP monitoring device. RESULTS: Intracranial pressure decreased after the combination of craniectomy, durotomy, and other ICP-lowering treatments in dogs of experiment A. Similar magnitude of decrease in ICP was observed in dogs of experiment B after craniectomy and durotomy. CONCLUSIONS: Comparison of these experiments indicate that surgical removal of overlying skull and incision of the dura mater can significantly decrease ICP in clinically normal dogs. CLINICAL RELEVANCE: Craniectomy and durotomy may be useful as an adjunct treatment for increased ICP.

Adrenal Cortex Hormones

Brain imaging.

Advances in medical technology have revolutionized diagnostic brain imaging. Traditional radiography and invasive contrast studies for intracranial imaging have been superseded by several newer imaging modalities which provide high resolution, cross-sectional images. Ultrasonography, computed tomography, magnetic resonance, and nuclear scintigraphy are now used for anatomical and functional imaging of the brain. These noninvasive modalities are available at most veterinary teaching institutions and are offered through many larger referral practices. The diagnostic usefulness and clinical limitations for each of these modalities are described.

Animals

Intraoperative monitoring of intracranial pressure in five dogs with space-occupying intracranial lesions.

Five dogs with space-occupying intracranial lesions underwent lateral craniectomy. Brain tissue pressures, reflective of intracranial pressure, were monitored during the surgical procedure, using a fiberoptic intracranial pressure monitoring system. The intracranial pressure monitoring cable was placed superficially in brain parenchyma on the side contralateral to the primary lesion. Recordings were made continually throughout the surgical procedure. Each dog was treated preoperatively with mannitol, which caused a decrease in intracranial pressure prior to craniectomy in only those dogs that initially had high intracranial pressure. Complications associated with use of the fiberoptic intracranial monitoring system were not evident. Although absolute values for pressure varied, pressure trends were helpful in determining effects of surgical manipulations on intracranial pressure in these dogs.

Animals

Central nervous system tumors.

Central nervous system (CNS) tumors are relatively common in veterinary medicine, with most diagnoses occurring in the canine and feline species. Numerous tumor types from various cells or origins have been identified with the most common tumors being meningiomas and glial cell tumors. Radiation therapy is often used as an aid to control the clinical signs associated with these neoplasms. In general, these tumors have a very low metastatic potential, such that local control offers substantial benefit. Experience in veterinary radiation oncology would indicate that many patients benefit from radiation treatment. Current practice indicates the need for computed tomography or magnetic resonance imaging studies. These highly beneficial studies are used for diagnosis, treatment planning, and to monitor treatment response. Improvements in treatment planning and radiation delivered to the tumor, while sparing the normal tissues, should improve local control and decrease potential radiation related problems to the CNS. When possible, multiple fractions of 3 Gy or less should be used. The tolerance dose to the normal tissue with this fractionation schedule is 50 to 55 Gy. The most common and serious complications of radiation for CNS tumors is delayed radiation myelopathy and necrosis. Medical management of the patient during radiation therapy requires careful attention to anesthetic protocols, and medications to reduce intracranial pressure that is often elevated in these patients. Canine brain tumors have served as an experimental model to test numerous new treatments. Increased availability of advanced imaging modalities has spawned increased detection of these neoplasms. Early detection of these tumors with appropriate aggressive therapy should prove beneficial to many patients.

Animals

Large animal normal tissue tolerance with boron neutron capture.

PURPOSE: Normal tissue tolerance of boron neutron capture irradiation using borocaptate sodium (NA2B12H11SH) in an epithermal neutron beam was studied. METHODS AND MATERIALS: Large retriever-type dogs were used and the irradiations were performed by single dose, 5 x 10 dorsal portal. Fourteen dogs were irradiated with the epithermal neutron beam alone and 35 dogs were irradiated following intravenous administration of borocaptate sodium. RESULTS: Total body irradiation effect could be seen from the decreased leukocytes and platelets following irradiation. Most values returned to normal within 40 days postirradiation. Severe dermal necrosis occurred in animals given 15 Gy epithermal neutrons alone and in animals irradiated to a total peak physical dose greater than 64 Gy in animals following borocaptate sodium infusion. Lethal brain necrosis was seen in animals receiving between 27 and 39 Gy. Lethal brain necrosis occurred at 22-36 weeks postirradiation. A total peak physical dose of approximately 27 Gy and blood-boron concentrations of 25-50 ppm resulted in abnormal magnetic resonance imaging results in 6 months postexamination. Seven of eight of these animals remained normal and the lesions were not detected at the 12-month postirradiation examination. CONCLUSION: The bimodal therapy presents a complex challenge in attempting to achieve dose response assays. The resultant total radiation dose is a composite of low and high LET components. The short track length of the boron fission fragments and the geometric effect of the vessels causes much of the intravascular dose to miss the presumed critical target of the endothelial cells. The results indicate a large dose-sparing effect from the boron capture reactions within the blood.

Animals

Biodistribution of boron in dogs with spontaneous intracranial tumors following borocaptate sodium administration.

Borocaptate sodium (Na2B12H11SH) is a potentially useful compound for boron neutron capture therapy of intracranial tumors. Tumor and normal tissue boron concentrations were evaluated in 30 dogs with naturally occurring intracranial tumors after i.v. borocaptate sodium infusion (55 mg boron/kg). Postmortem tissue boron concentrations were measured for three postinfusion time periods (2, 6, and 12 h) by inductively coupled plasma atomic emission spectroscopy. Mean boron concentrations for extracerebral tumors were 40.6 +/- 16.9 (2 h; n = 8), 25.9 +/- 11.7 (6 h; n = 5), and 8.6 +/- 4.5 micrograms boron/g (12 h; n = 6). Mean boron concentrations for intracerebral tumors were 30.6 +/- 17.5 (2 h; n = 7) and 2.9 +/- 1.8 micrograms boron/g (6 h; n = 4). Mean tumor boron concentrations were lower at longer postinfusion times. The tumor:normal brain boron concentration ranged from 0.8 to 19.8. Tumor:blood boron concentrations were less than one for all but three dogs and ranged from 0.04 to 1.4. Mean peritumor boron concentrations were highly variable but exceeded that of normal brain in 10 of 20 dogs. In some dogs, the mean peritumor boron concentration was similar to or exceeded the tumor boron concentration. Distant or contralateral normal brain had consistently low boron concentrations. Some cranial and systemic tissues had high boron concentrations, indicating substantial extravascular boron. The spontaneous animal tumors provided a realistic spectrum of data and enabled extensive sampling of diseased and normal tissues. The biodistribution of boron from borocaptate sodium administration was partially favorable because of high tumor boron concentrations. Empirical radiation dose tolerance studies should be used to determine the impact of the unfavorably high boron concentration of blood and some cranial tissues.

Adenoma

Pharmacokinetics in melanoma-bearing mice of 5-dihydroxyboryl-6-propyl-2-thiouracil (BPTU), a candidate compound for boron neutron capture therapy.

Blood pharmacokinetics and tissue distribution of 5-dihydroxyboryl-6-propyl-2-thiouracil (BPTU), a boron carrier with postulated melanin-seeking properties for boron neutron capture therapy, were determined in C57/BL mice with subcutaneous pigmented or non-pigmented B16 melanomas. Borocaptate sodium (BSH) was used as a boron compound without melanin-seeking properties in a comparative biodistribution study in the same animal tumour models. Administration of single doses showed that BPTU was retained better in the pigmented B16 tumour than in the non-pigmented variant. BPTU was found in large concentrations in kidney and liver. Brain boron was approximately 10-fold lower than tumour boron. On a molar basis, BPTU demonstrated higher affinity for B16 tumours than BSH. Owing to solubility limits, tumour boron concentrations in this mouse study were too low for effective application of BNCT. However, the high tumour-to-blood and tumour-to-normal tissues ratios indicate that, with appropriate formulation, BPTU could be a promising candidate for clinical BNCT.

Animals

Thromboxane as a measure of cutaneous vascular damage following irradiation.

The present study was designed to evaluate the role of thromboxane in radiation-induced cutaneous injury and to use the quantitation of cutaneous thromboxane B2 as an indicator of vascular alteration and tissue viability in canine skin. Ten adult intact male dogs underwent epithermal neutron irradiation with or without boron neutron capture. Skin biopsies were obtained from (1) within, (2) the edge of, and (3) outside the radiation field at 5, 8, 11, 14, 21, and 90 days after irradiation. Clinical changes at each sampling time were assigned a numerical score. One-half of each biopsy was assigned a numerical score based on histologic changes. Thromboxane B2 was measured from the second half by enzyme immunoabsorbent assay. Thromboxane B2 concentration paralleled the response of clinical and histologic score over time, indicating the value of thromboxane measurement for evaluation of skin changes secondary to irradiation.

Animals

Comparison of computed tomography with radiography as a noninvasive diagnostic technique for chronic nasal disease in dogs.

Computed tomography was evaluated as a noninvasive technique for the diagnosis of chronic nasal disease in dogs. Computed tomographic images, radiographs, and histopathologic findings were compared in 11 dogs with chronic nasal disease. Definitive diagnosis was made following traumatic nasal flush, exploratory surgery, or necropsy. The study included 8 dogs with intranasal tumors, 2 dogs with bacterial rhinitis (Pasteurella sp), and 1 dog with mycotic rhinitis (Aspergillus sp). Computed tomography was superior to radiography in defining the extent of the disease process and in differentiating infectious rhinitis from nasal neoplasms. It defined lesions in the palate, nasopharyngeal meatus, maxillary sinus, caudal ethmoturbinates, and periorbital tissues that were difficult to demonstrate by use of conventional radiography. Tumors appeared as space-occupying lesions that obliterated the turbinates, caused deviation of the nasal septum, and eroded bone. Rhinitis appeared as a cavitating lesion that spared the paranasal sinuses, thickened and distorted the turbinates, and widened the meatus. Although morphologically distinct on computed tomographic images, infectious rhinitis and nasal neoplasms could not be differentiated by attenuation measurements or degree of contrast enhancement. Computed tomography appeared to be a reliable, noninvasive technique for the diagnosis of chronic nasal disease in dogs, and a promising alternative to diagnostic techniques currently in use.

Animals

Large animal normal tissue tolerance using an epithermal neutron beam and borocaptate sodium.

Irradiation of the canine head following intravenous Na2B12H11SH (BSH) administration has provided useful information concerning the tolerance of skin and brain to the resultant complex form of irradiation. The effect of the boron capture reaction in skin and brain has provided estimates of the influence of the microscopic dosimetry involved. Dogs irradiated with the epithermal beam alone provided valuable insight into the relative biological effectiveness (RBE) of the fast neutron component (> 10 keV) of the epithermal beam. When compared with literature values for X-rays for the occurrence of skin necrosis in dogs, an RBE of 4.5 was derived. Previous pharmacokinetic data concerning the distribution of Na2B12H11SH (BSH) to blood and brain has been used to obtain input parameters for computer models of the microvasculature of the brain. Monte Carlo computer models were used to simulate the microscopic distribution of BSH in the normal brain. The term compound factor describes the product of the microscopic boron fission fragment dose hitting the nucleus and the relative biologic effectiveness divided by the macroscopic equilibrium dose of the boron reaction in the tissue of interest. The computed compound factor for Na2B12H11SH (BSH) in normal brain was 0.37. This factor agreed very well with the value of 0.32 obtained for the brain necrosis with the dog irradiations. The compound factor for the dog's skin was experimentally derived from the dog experiments and was equal to 0.5.

Animals