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Biomedical subjects

S M Griffey

Publications and source records attributed to S M Griffey.

At least 37 records · Page 2Linked to original sources
PubMed1999

Comparison of perioperative versus postoperative intratumoral administration of cisplatin for treatment of cutaneous sarcoids and squamous cell carcinomas in horses.

OBJECTIVE: To determine the benefits of reducing the interval between surgical cytoreduction and intratumoral administration of cisplatin. DESIGN: Randomized clinical study. ANIMALS: 70 horses with 89 incompletely resected T2- and T3-stage sarcoids (n = 64) and squamous cell carcinomas (25). PROCEDURE: Horses were given 4 intratumoral treatments of cisplatin at 2-week intervals. The first treatment was given at the time of, or immediately after, surgical resection for horses treated in accordance with the perioperative protocol (group 1). Horses in group 2 were treated with cisplatin after the skin healed following surgical resection in accordance with the postoperative protocol. RESULTS: A difference was not found in duration of overall local tumor control between the 2 groups. Patterns of treatment failures and interval to failure differed between the 2 groups. Length of the surgical scar was the only factor that affected prognosis; an increase in length was associated with a poorer prognosis. A detrimental effect of postoperative treatment was only found in tumors with a high tumor proliferative fraction. Local reactions were similar for the 2 treatment groups, and chronic reactions were not observed. CONCLUSIONS AND CLINICAL RELEVANCE: Intratumoral administration of cisplatin is beneficial for treatment of cutaneous tumors in horses. Tumor repopulation during the interval between surgery and intratumoral administration of cisplatin decreases treatment efficacy. These results provide evidence of rapid tumor repopulation following surgical resection without a lag period for tumors with a high proliferation index. When tumor proliferation index is not known, it may be prudent to use the perioperative protocol.

Animals↗
PubMed1999

Radiofrequency ablation of breast cancer: first report of an emerging technology.

HYPOTHESIS: Radiofrequency (RF) energy applied to breast cancers will result in cancer cell death. DESIGN: Prospective nonrandomized interventional trial. SETTING: A university hospital tertiary care center. PATIENTS: Five women with locally advanced invasive breast cancer, aged 38 to 66 years, who were undergoing surgical resection of their tumor. One patient underwent preoperative chemotherapy and radiation therapy, 3 patients received preoperative chemotherapy, and 1 had no preoperative therapy. All patients completed the study. INTERVENTIONS: While patients were under general anesthesia and just before surgical resection, a 15-gauge insulated multiple-needle electrode was inserted into the tumor under sonographic guidance. Radiofrequency energy was applied at a low power by a preset protocol for a period of up to 30 minutes. Only a portion of the tumor was treated to evaluate the zone of RF ablation and the margin between ablated and nonablated tissue. Immediately after RF ablation, the tumor was surgically resected (4 mastectomies, 1 lumpectomy). Pathologic analysis included hematoxylin-eosin staining and enzyme histochemical analysis of cell viability with nicotinamide adenine dinucleotide-diaphorase (NADH-diaphorase) staining of snap-frozen tissue to assess immediate cell death. MAIN OUTCOME MEASURE: Cancer cell death as visualized on hematoxylin-eosin-stained paraffin section and NADH-diaphorase cell viability stains. RESULTS: There was evidence of cell death in all patients. Hematoxylin-eosin staining showed complete cell death in 2 patients. In 3 patients there was a heterogeneous pattern of necrotic and normal-appearing cells within the ablated tissue. The ablated zone extended around the RF electrode for a diameter of 0.8 to 1.8 cm. NADH-diaphorase cell viability stains of the ablated tissue showed complete cell death in 4 patients. The fifth patient had a single focus of viable cells (<1 mm) partially lining a cyst. There were no perioperative complications related to RF ablation. CONCLUSIONS: Intraoperative RF ablation results in invasive breast cancer cell death. Based on this initial report of the use of RF ablation in breast cancer, this technique merits further investigation as a percutaneous minimally invasive modality for the local treatment of breast cancer.

Adult↗
PubMed1999

Lymph node uptake of interstitially delivered particulate contrast media before and after irradiation in dogs.

RATIONALE AND OBJECTIVES: The authors' purpose was to assess the effects of ionizing radiation on the uptake and distribution of interstitially delivered particulate contrast medium in normal lymph nodes in dogs. MATERIALS AND METHODS: Two milliliters of an iodinated nanoparticle suspension (NC 67722 Sterile Suspension, 76 mg of iodine per milliliter) was injected subcutaneously or submucosally into nine normal adult beagle dogs. Targeted lymph node groups were evaluated with computed tomography (CT). Region-of-interest analysis was used to estimate volume, attenuation, and iodine concentration of the opacified nodes and nonopacified contralateral nodes on CT images obtained before and 24 hours after the injection. All right-sided and some left-sided lymph nodes were irradiated with 50 Gy in 25 fractions of 2 Gy per day, beginning 28-35 days after the CT examination. Contrast medium administration and quantitative CT imaging were performed again 3 months after irradiation. RESULTS: Contrast material uptake resulted in a twofold increase in node volume before irradiation (P < .0001). Mean attenuation of contrast-enhanced nodes increased to 230-330 HU from a precontrast enhancement value of 36.5 HU. After irradiation, opacified node volumes decreased to approximately 25%-50% of their preirradiation volumes (P < .02). Contrast material uptake decreased 10%-15% after irradiation but was not significantly less than preirradiation uptake. Qualitatively, no substantial difference in contrast material distribution existed between irradiated and nonirradiated nodes. CONCLUSION: An elective irradiation dose decreased lymph node size, but the imaging characteristics of opacification were not otherwise appreciably altered 3 months after irradiation.

Analysis of Variance↗
PubMed1999

Proliferation indices in spontaneous canine lung cancer: proliferating cell nuclear antigen (PCNA), Ki-67 (MIB1) and mitotic counts.

Proliferation indices were measured for specimens from 55 spontaneous canine lung tumours, collected by surgical biopsy from clinical patients and archived in paraffin wax blocks. These indices were then related to the mitotic index and histological type of the tumour. Proliferating cell nuclear antigen (PCNA) and Ki-67 (MIB1) proteins were detected immunohistochemically with a biotin-streptavidin amplified detection system on a representative tissue section from each tumour. Five adjacent, non-overlapping fields were selected at random, and 200 cells per field were examined in each section. For PCNA, cells were classified subjectively into negative, weak or strong reactivity groups, based on nuclear staining. MIB1 cells were classified as negative or positive, based on nuclear staining. Mitotic figures were counted in anti-PCNA-labelled and anti-MIB1-labelled sections, in the same tumour areas as those in which indices were established. Mitotic counts were also done on haematoxylin and eosin-stained tissue sections. Linear regression analysis showed that all PCNA, MIB1 and mitotic indices had highly significant positive correlations (P<0.0001) with each other. Adenosquamous and squamous cell carcinomas differed from other histological tumour types in having significantly higher proliferation indices. These data suggest that growth rates for lung tumours in the dog vary according to histological type. On the basis of differences in proliferation indices and the distribution of immunoreactivity between histological subtypes in this study, it would seem that immunohistochemical detection of PCNA and MIB/1 reactivity and analysis of mitotic figures in routinely processed tissues may be useful in the diagnosis of lung tumours. 1999 W.B. Saunders and Company Ltd.

Adenocarcinoma↗
PubMed1999

Topographic distribution of bcl-2 protein in feline tissues in health and neoplasia.

The bcl-2 family of genes encodes proteins that influence apoptosis. In the present immunohistochemical study, the topographic distribution of bcl-2 protein was examined in healthy feline fetal, neonatal, and adult tissues, a feline renal cell line, and feline tumors obtained from a veterinary hospital. The topographic distribution of bcl-2 in healthy tissues was similar to that described in human tissues. In lymphoid tissues, follicular mantle cells strongly expressed bcl-2. In complex and differentiating epithelium, bcl-2 expression was detected in stem cell and proliferation zones. Bcl-2 expression was also detected in lower crypts of the intestine and in skin basal layers. The feline Crandell kidney cells expressed bcl-2 diffusely throughout the cytoplasm. Of 180 tumors examined, bcl-2 was expressed almost uniformly in cutaneous basal cell tumors, thyroid adenomas, and mammary carcinomas and in 50% of the lymphomas examined. Bcl-2 may play a role in blocking apoptotic cell death in a broad range of normal feline tissues, whereas dysregulated bcl-2 may extend the life of certain tumors or render certain tumors resistant to therapy because most chemotherapeutic and radiotherapeutic agents eliminate tumor cells by triggering apoptosis.

Animals↗
PubMed1999

Preclinical study in cats of the pro-photosensitizer 5-aminolevulinic acid.

OBJECTIVE: To determine whether feline cells were able to convert 5-aminolevulinic acid (ALA) to protoporphyrin IX (PpIX) in vivo and in vitro, whether i.v. administration of ALA to healthy cats resulted in adverse effects, and whether PpIX accumulated in a squamous cell carcinoma (SCC) of a cat. ANIMALS: 4 healthy adult cats and 1 adult cat with a cutaneous SCC. PROCEDURE: In vitro production of PpIX was determined by incubating Crandell feline kidney cells with ALA. Effects of ALA administration and in vivo production of PpIX were determined by administering ALA (100, 200, or 400 mg/kg of body weight) to healthy cats and collecting skin biopsy specimens for up to 24 hours after drug administration. Blood samples were collected for CBC and serum biochemical analyses, and necropsies were performed. Accumulation of PpIX in a SCC was determined by treating a cat with a facial SCC with ALA and collecting specimens of the tumor and adjacent grossly normal skin. RESULTS: Incubation of ALA with feline cells resulted in time- and dose-dependent cytoplasmic accumulation of PpIX in vitro. After i.v. ALA administration, PpIX was detected in all tissues examined, with the highest fluorescence intensity in epithelia and in squamous cell carcinoma. The tumor-to-skin fluorescence intensity ratio was 5. All cats developed hepatotoxicoses. CONCLUSIONS AND CLINICAL RELEVANCE: Results from this limited number of cats suggest that ALA may be a useful photosensitizer in cats, but that doses > 100 mg/kg, i.v., may not be safe.

Aminolevulinic Acid↗
PubMed1998

K-ras mutations in 239PuO2 canine lung neoplasms.

Single-strand conformational polymorphism (SSCP) analysis and direct sequencing methods were used to examine lung tumors derived from a cohort of beagle dogs with inhalational exposures to 239PuO2. These exposures were done at Pacific Northwest Laboratories where 18-month-old beagle dogs were given 239PuO2 by single-dose inhalation and allowed to live out their life-spans. Formalin-fixed paraffin-embedded blocks of tissues from 25 dogs exposed to 239PuO2 by aerosol inhalation which later developed lung tumors were available for this study. Two of 25 tumors had mutations within exon 1 of K-ras detected by SSCP analysis. Both mutations were GGT to GAT transitions at codon 12 confirmed by direct sequencing experiments. One was an adenocarcinoma from the medium-high exposure group and the other was a broncheolo-alveolar carcinoma from the medium-low exposure group. The rate of K-ras mutations in plutonium-induced lung tumors described herein (8%) was greater than previously described in canine plutonium-induced lung tumors (0%), but was less than that which we have described in spontaneous canine lung cancer (16%), less than that reported for human spontaneous non-small cell lung cancer (13-36%) and less than that described in rats with spontaneous lung cancer (40%) or lung tumors following 239Pu inhalation exposure (46%).

Administration, Inhalation↗
PubMed1998

Amelogenin expression in canine oral tissues and lesions.

Amelogenins are major enamel proteins within the enamel extracellular matrix. The expression of amelogenin was confirmed in neonatal tissues of the canine jaw. The sequence of a portion of canine amelogenin cDNA, within exons 5 and 6, was determined and found to be closely homologous to sequences reported in the cow, pig, mouse and human being. Two acanthomatous epulides collected from clinically affected dogs showed amelogenin expression, whereas 22 other canine oral lesions, including six additional acanthomatous epulides, did not show amelogenin expression. Examination of structural proteins may allow precise identification of the histogenesis of the odontogenic neoplasms, which are often difficult to distinguish by means of morphological criteria alone.

Ameloblastoma↗
PubMed1998

Rapid detection of K-ras gene mutations in canine lung cancer using single-strand conformational polymorphism analysis.

A total of 126 spontaneous lung tumors from pet dogs were examined for K-ras mutations within exon 1 and exon 2 using a non-radioisotope single-strand conformational polymorphism analysis (SSCP) detection method on PCR products. Mutations were confirmed by direct DNA sequencing. Tumors were classified as adenomas (9), bronchioloalveolar carcinomas (59), adenocarcinomas (30), adenosquamous carcinomas (16), squamous cell carcinomas (3) and anaplastic carcinomas (9). Nineteen mutations were detected in the malignant tumors: 18 occurred in exon 1 codon 12 and one in exon 2 codon 61. No mutations were present in the adenomas. The most common mutation was a G-->A transition (11/19) in the second position of codon 12. Based on this study, K-ras mutations occur in canine non-small cell lung carcinomas. The frequency and type of mutation more closely matches tumors from human non-smokers with K-ras mutations than smokers. With the application of screening techniques such as SSCP, large numbers of dog tumors can be examined to provide a large animal model for comparative studies of carcinogenesis.

Animals↗
PubMed1998

Meal patterns associated with the age-related decline in food intake in the Fischer 344 rat.

We previously reported that aging Fischer 344 (F344) rats display a spontaneous, rapid loss in body weight associated with decreased food intake near the end of life. Here, we describe the specific changes in feeding patterns underlying this reduced intake. Nine male F344 rats, aged 25 mo, were monitored continuously until 7 days after the onset of spontaneous rapid weight loss (i.e., senescence). Regardless of age at death (25.5-32.5 mo), all senescent rats demonstrated a similar pattern of decreased food intake. They ate significantly smaller meals (g/meal) of shorter duration during spontaneous rapid weight loss compared with their period of weight stability (presenescence). However, no differences occurred in the number of meals eaten per day. Rapid weight loss had no effect on the rats' selection of preferred diets. Serum levels of the hormone leptin were not higher in the senescent vs. age-matched presenescent rats, nor was the incidence of common disease different in senescent animals. Moreover, the area of the pituitary-hypothalamus interface, measured to identify possible hypothalamic compression, was similar in the senescent rats and an age-matched, presenescent control group despite significantly greater pituitary size in the former. Our data show that simultaneous with rapid spontaneous weight loss, aging rats demonstrate significant changes in feeding patterns suggestive of earlier satiation. These feeding alterations do not result from loss of ability to select for palatable food, elevated serum leptin levels, specific pathology, or hypothalamic compression.

Aging↗
PubMed1998

Computer-assisted image analysis of intratumoral vessel density in mammary tumors from dogs.

OBJECTIVE: To determine whether intratumoral microvessel density can be used to distinguish benign from malignant mammary tumors in dogs and to predict the outcome of surgical treatment for small volume (< 3-cm diameter) tumors. SAMPLE POPULATION: Tissue sections from 58 mammary tumors (42 malignant and 16 benign) from dogs. PROCEDURE: Mammary tumors were stained by immunohistochemistry for factor VIII-related antigen. Computer-assisted image analysis was used to determine intratumoral vessel density in immunostained areas. Total vascular density (TVD), calculated from 3 non-overlapping fields, was analyzed for correlation with patient or tumor histomorphologic characteristics, and results obtained by surgical treatment of small volume tumors. RESULTS: Mean TVD of malignant tumors was significantly greater than that of benign tumors. Total vascular density was not correlated with patient age, sex, reproductive status, clinical tumor stage, or histologic type. For small volume (< 3-cm diameter) malignant tumors, mean TVD was higher in tumors that recurred after surgery than in tumors that did not recur; however, TVD was not predictive of time to recurrence. CONCLUSION AND CLINICAL IMPLICATIONS: Immunohistochemistry and computer-assisted image analysis allowed objective quantitation of intratumoral microvessel density in formalin-fixed, paraffin-embedded tissue sections. Tumors with high TVD were more likely to recur after surgical treatment than tumors with low TVD suggesting that TVD measurements can be used by the clinician, in addition to histologic type and clinical stage, to predict prognosis after surgical treatment. These data also provide rationale for use of antiangiogenesis strategies for treatment of malignant mammary tumors in dogs.

Angiography↗
PubMed1997

Combination leflunomide and cyclosporine prevents rejection of functional whole limb allografts in the rat.

Whole rear limbs were transplanted from Brown Norway or Lewis rat donors to Lewis rat recipients (n=6 per group). One group of allograft recipients was treated with leflunomide (10 mg/kg/24 hr/orally) and cyclosporine (5 mg/kg24 hr/orally) starting 2 days before to surgery. Treatment continued for 60 days or until graft rejection. Untreated allografts were rejected over 6-8 days. After isograft transplantation, weight bearing began by day 17-25 after surgery. Sensory function was restored by 50 days after surgery. All allografts in the drug-treated group survived the 60-day period; survival in this group was significantly longer (P=0.0001) than the untreated controls. Weight bearing began by day 30, but was incomplete in two rats at 60 days. Peroneal nerve function was present in half the rats at 60 days after surgery. Leflunomide combined with cyclosporine prevented whole limb allograft rejection across a major histocompatibility barrier.

Animals↗
PubMed1997

Diabetic ketosis and ketoacidosis in cats: 42 cases (1980-1995).

OBJECTIVE: To determine clinical signs, clinicopathologic abnormalities, prevalence of concurrent disease, treatment, complications of treatment, and outcome in cats with diabetic ketosis (DK) or diabetic ketoacidosis (DKA). DESIGN: Retrospective study. ANIMALS: 42 cats with DK or DKA. PROCEDURE: Medical records of diabetic cats with ketonuria were reviewed. RESULTS: In 26 cats, diabetes was newly diagnosed; in 16, diabetes had been diagnosed previously and cats had been treated with insulin (n = 14) or sulfonylurea drugs (2). Common clinical findings were lethargy, anorexia, polyuria, polydipsia, and weight loss. Common laboratory findings were hyperglycemia, hyponatremia, hypochloremia, hypokalemia, hypocalcemia, hypophosphatemia, low total CO2 content, hyperosmolality, high serum alanine transaminase activity, azotemia, glycosuria, and ketonuria. Concurrent disorders were identified in 39 cats and included hepatic lipidosis, cholangiohepatitis, pancreatitis, chronic renal failure, urinary tract infection, and neoplasia. Treatment of DK and DKA included administration of regular crystalline (34 cats), NPH (6), or ultralente (2) insulin, intravenous (38) or subcutaneous (4) administration of fluids, and enterall parenteral or administration of antibiotics (42). Complications during treatment included abnormalities in serum electrolyte concentrations (27 cats), hemolytic anemia (4), hypoglycemia (3), and neurologic abnormalities unrelated to hypoglycemia (2). Eleven cats died or were euthanatized during the initial hospitalization period for treatment of DK or DKA. Azotemia, metabolic acidosis, and hyperosmolality were more severe in cats that died than in cats that survived. Differences in regard to treatment or complications were not apparent between cats that died and cats that survived. The 31 cats that survived were discharged 1 to 16 days (median, 5 days) after initiation of insulin treatment. Diabetic ketosis or ketoacidosis recurred in 13 (42%) of these cats. CLINICAL IMPLICATIONS: A thorough diagnostic evaluation should be performed on cats with DK or DKA to identify concurrent disorders, formulate an appropriate treatment plan, and provide prognostic information to the owner.

Alanine Transaminase↗
PubMed1997

The atopic dog: a model for food allergy.

The renewed interest in food allergy and its investigation has been hampered by the lack of an appropriate animal model with similar comparative aspects of form and function relative to humans. Therefore we have been characterizing an inbred colony of high immunoglobulin E-producing dogs that were immunized subcutaneously with food antigen extracts in alum and that developed clinical manifestations of food allergy after oral challenges with food antigen. These dogs had appreciably high IgE antibody titer to specific food antigens, as measured by an enzyme-labeled immunodot assay. Skin test results for the food antigens were consistently positive, as evidenced by a wheal-and-flare reaction. Gastroscopic food sensitivity was tested through an endoscope by injecting allergenic food extracts into the gastric mucosa after intravenous injection of Evans blue dye. Mucosal changes included swelling and erythema, some petechiae and blue patching, and in some instances generalized gastric erythema and hyperperistalsis. Examination of immediate-reaction biopsy specimens revealed edema and few inflammatory cells. Examination of late-reaction biopsy specimens revealed increased eosinophil and mononuclear cell infiltrations typical of late-phase allergic inflammatory responses. Direct mucosal challenge with food extracts confirmed the clinical and immunologic evidence of food allergy in these immunized dogs and suggests the usefulness of the atopic dog as a model for food allergy. This model might also be useful in detecting hidden food allergies in unexplained inflammatory gastrointestinal tract diseases.

Animals↗
PubMed1996

Central diabetes insipidus in dogs: 20 cases (1986-1995).

OBJECTIVE: To assess clinical signs, biochemical findings, results of modified water deprivation and other diagnostic tests, response to treatment, and survival time in dogs with central diabetes insipidus (CDI). DESIGN: Retrospective study. ANIMALS: 20 dogs with CDI. PROCEDURE: Signalment, history, physical examination, results of diagnostic tests, response to treatment, and survival time were extracted from the medical record of each dog and supplemented with information obtained from owners via telephone. RESULTS: Isosthenuria or hyposthenuria was a consistent finding. Seven dogs with complete CDI and 13 dogs with partial CDI were identified on the basis of results of a modified water deprivation test. Dogs treated with desmopressin acetate responded well to treatment. Seven dogs were alive 18 to 72 months (median, 36 months) after diagnosis, and 10 dogs died or were euthanatized 1 week to 2 years (median, 2 months) after diagnosis. Seven of 10 dogs that died developed neurologic signs after diagnosis of CDI. Computed tomography revealed a mass in the region of the pituitary gland in 5 of 7 dogs. Necropsy of 6 dogs, including 2 dogs on which computed tomography had been performed, revealed neoplasia in the pituitary gland. CLINICAL IMPLICATIONS: Onset of neurologic signs after diagnosis of CDI in middle- to old-aged dogs indicates that CDI may not be a benign disease that is treated easily. Brain imaging is recommended after diagnosis of CDI in middle- to old-aged dogs. Also, because many dogs are isosthenuric on initial examination, CDI cannot be ruled out as a cause of polyuria and polydipsia on the basis of lack of hyposthenuria.

Animals↗
PubMed1996

Analysis of the equine tumor suppressor gene p53 in the normal horse and in eight cutaneous squamous cell carcinomas.

Wild type equine p53 was amplified between exons 2 and 9 by the polymerase chain reaction using primers designed from conserved regions in other species. An 828 base pair region, corresponding to codons 25-313 of human p53, was sequenced in both directions. Human and equine amino acid sequences were 87% homologous in this region and 96% homologous in conserved domains II-V. Of eight equine cutaneous or mucocutaneous squamous cell carcinomas directly sequenced from exons 5-8, two had p53 point mutations resulting in single amino acid substitutions.

Amino Acid Sequence↗
PubMed1996

Effects of leflunomide and cyclosporine on myocutaneous allograft survival in the rat.

The immunosuppressive effects of leflunomide and cyclosporine were evaluated in a rat neurovascularized myocutaneous allograft model. Inbred Brown-Norway and Lewis rats were served as donors and recipients, respectively. All recipients were observed for 60 days or until allograft rejection occurred. All isograft controls (Lewis to Lewis, n=6) survived uneventfully. All control allografts (n=6) were rejected within 6 days. Allograft recipients (n=6) administered leflunomide (10 mg/kg/24 hr) rejected their allografts in 28.50+/-6.12 days, and allograft recipients (n=6), administered cyclosporine (5 mg/kg/24 hr) rejected their allografts in 24.33+/-10.48 days. When allograft recipients were administered a combination of leflunomide and cyclosporine (10 mg/kg/24 hr and 5 mg/kg/24 hr, respectively), all allografts survived to 60 days with only partial rejection of the skin of one graft. The neuromuscular function of the allografts of the rats receiving combination therapy was comparable to that of the isografts. The combination of leflunomide and cyclosporine controlled myocutaneous allorejection despite a strong immunological challenge.

Animals↗