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Abstract

Objective—To determine whether epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) are expressed in periocular squamous cell carcinomas (SCCs) of horses.

Sample—Biopsy specimens of SCCs from 46 horses.

Procedures—Pathology records were searched retrospectively for biopsy specimens of periocular SCCs obtained from horses. Slides of the specimens were reviewed histologically to confirm the SCC diagnosis and stained for EGFR and HER2 by immunohistochemical methods. For both EGFR and HER2, the immunohistochemical staining intensity and percentage of stain-positive cells on the slides were determined.

Results—43 of 46 (93%) SCCs were immunoreactive for EGFR. The median score for EGFR staining intensity was 4 (range, 2 to 12), and the median number of mitotic figures was 8 mitotic figures/10 hpfs (range, 0 to 34 mitotic figures/10 hpfs). Mitotic index was not correlated with the percentage of EGFR stain–positive cells or staining intensity. Of the 43 EGFR-immunoreactive SCCs, 38 had stain present primarily in the cytoplasm and 5 had stain equally distributed between the cytoplasm and cell membranes. Thirty-five of 46 (76%) SCCs were immunoreactive for HER2. Mitotic index was not correlated with the percentage of HER2 stain–positive cells or staining intensity. Of the 35 HER2-immunoreactive SCCs, the stain was present primarily in the cytoplasm and 7 had stain equally distributed between the cytoplasm and cell membranes.

Conclusions and Clinical Relevance—Results indicated that most periocular SCCs of horses expressed EGFR and HER2, which suggested that equine periocular SCCs might respond to treatment with EGFR inhibitors.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate the outcome and describe the complications associated with use of an Ahmed gonioimplant in the treatment of glaucoma in dogs.

Design—Retrospective case series.

Animals—9 client-owned sighted dogs (median age, 9 years) with primary glaucoma.

Procedures—Medical records of dogs with primary glaucoma that underwent unilateral gonioimplant placement (in 2000 through 2008), during which a temporalis muscle fascia graft (n = 8) or porcine intestinal submucosa (1) was used to cover the implant tube as it exited the globe, were reviewed. All dogs were treated with mitomycin C in the conjunctival pocket intraoperatively and with tissue plasminogen activator immediately after surgery; 1% prednisolone acetate was applied to the implanted eye daily until failure of the implant. Medical intervention or additional surgery was performed when intraocular pressures (IOPs) were > 20 mm Hg or progressively increasing values were detected.

Results—After gonioimplant placement, IOP was controlled for a variable period in all dogs. Subsequently, IOP exceeded 20 mm Hg in 7 dogs (median postoperative interval, 326 days). Median interval to vision loss despite interventional surgery was 518 days (range, 152 to 1,220 days). Surgical intervention was necessary in 4 dogs to maintain satisfactory IOP. Implant extrusion attributable to conjunctival dehiscence or necrosis occurred in 4 dogs. At 365 days after surgery, 8 dogs retained vision, and 5 dogs retained vision throughout follow-up.

Conclusions and Clinical Relevance—In dogs with medically refractory primary glaucoma, placement of a gonioimplant appears to be effective in maintaining vision.

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in Journal of the American Veterinary Medical Association

Abstract

Objective—To determine magnitude and duration of the effect of oral administration of methazolamide at 2 dosages on intraocular pressure (IOP) in dogs in single- dose and multiple-dose trials and to determine aqueous humor flow rate (AHFR) by use of anterior segment fluorophotometry before and during treatment.

Animals—25 healthy adult Beagles.

Procedure—Baseline IOPs and AHFRs were determined on days 0 and 1, respectively. On day 2, the single-dose trial was initiated with oral administration of 25 or 50 mg of methazolamide at 7 AM to 2 groups of 10 dogs each. Five dogs served as controls. In the multiple-dose trial, the same dogs received 25 or 50 mg of methazolamide at 7 AM and at 3 and 11 PM on days 3 through 9.

Results—Intraocular pressures varied diurnally with highest IOPs in the morning. In the single-dose trial, IOP decreased significantly at 3 to 6 hours after treatment and then increased significantly at later time points, compared with baseline values. In the multipledose trial, dogs in both treatment groups had significantly lower IOPs during the treatment period at 10 AM and 1 PM but not at 6 and 9 PM, compared with baseline values. In both treatment groups morning IOPs had returned to baseline values by the first day after treatment. Evening IOPs were significantly increased by 2 to 3 days after treatment, compared with baseline values. The AHFRs in both treatment groups were significantly lower than pretreatment AHFRs.

Conclusions and Clinical Relevance—Oral administration of methazolamide decreases IOPs and AHFRs in clinically normal dogs, with effectiveness diminishing in the evening. (Am J Vet Res 2003;64:183–187)

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in American Journal of Veterinary Research

Abstract

OBJECTIVE To evaluate the tear film osmolality and electrolyte composition in healthy horses.

ANIMALS 15 healthy adult horses.

PROCEDURES Each horse was manually restrained, and an ophthalmic examination, which included slit-lamp biomicroscopy, indirect ophthalmoscopy, and a Schirmer tear test, was performed. Tear samples were collected from both eyes with microcapillary tubes 3 times at 5-minute intervals. The tear samples for each horse were pooled, and the osmolality and electrolyte concentrations were measured. The mean (SD) was calculated for each variable to establish preliminary guidelines for tear film osmolality and electrolyte composition in healthy horses.

RESULTS The mean (SD) tear film osmolality was 283.51 (9.33) mmol/kg, and the mean (SD) sodium, potassium, magnesium, and calcium concentrations were 134.75 (10), 16.3 (5.77), 3.48 (1.97), and 1.06 (0.42) mmol/L, respectively. The sodium concentration in the tear film was similar to that in serum, whereas the potassium concentration in the tear film was approximately 4.75 times that of serum.

CONCLUSIONS AND CLINICAL RELEVANCE Results provided preliminary guidelines with which tear samples obtained from horses with keratopathies can be compared. Measurement of tear film osmolality in these horses was easy and noninvasive. The tear film concentration of divalent cations was greater than expected and was higher than the divalent cation concentrations in the tear films of rabbits and humans. These data may be clinically useful for the diagnosis and monitoring of hyperosmolar ocular surface disease in horses.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the effects of topically applied 2% delta-9-tetrahydrocannabinol (THC) ophthalmic solution on aqueous humor flow rate (AHFR) and intraocular pressure (IOP) in clinically normal dogs.

Animals—21 clinically normal dogs.

Procedures—A randomized longitudinal crossover design was used. Following acquisition of baseline IOP (morning and evening) and AHFR (afternoon only) data, dogs were randomly assigned to 2 treatment groups and received 1 drop of either 2% THC solution or a control treatment (olive oil vehicle) to 1 randomly selected eye every 12 hours for 9 doses. The IOPs and AHFRs were reassessed after the final treatment. Following a washout period of ≥ 7 days, dogs were administered the alternate treatment in the same eye, and measurements were repeated.

Results—Mean ± SD IOPs in the morning were 15.86 ± 2.48 mm Hg at baseline, 12.54 ± 3.18 mm Hg after THC treatment, and 13.88 ± 3.28 mm Hg after control treatment. Mean ± SD IOPs in the evening were 13.69 ± 3.36 mm Hg at baseline, 11.69 ± 3.94 mm Hg after THC treatment, and 12.13 ± 2.99 mm Hg after control treatment. Mean IOPs were significantly decreased from baseline after administration of THC solution but not the control treatment. Changes in IOP varied substantially among individual dogs. Mean ± SD AHFRs were not significantly different from baseline for either treatment.

Conclusions and Clinical Relevance—Topical application of 2% THC ophthalmic solution resulted in moderate reduction of mean IOP in clinically normal dogs. Further research is needed to determine efficacy in dogs with glaucoma.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine aqueous humor flow rate in clinically normal dogs, using fluorophotometry.

Animals—20 clinically normal Beagles.

Procedure—A study was performed on 5 dogs to establish an optimal protocol for fluorophotometric determination of aqueous humor flow rate. This protocol then was used to measure aqueous humor flow rate in 15 dogs. Corneas were loaded with fluorescein by topical application, and corneal and aqueous humor fluorescein concentrations were measured 5, 6.5, and 8 hours after application. Concentration-versus- time plots were generated, and slopes and ratios of the fluorescein concentration in the cornea and aqueous humor from these graphs were used to calculate flow rates. Calculations were performed by use of automated software provided with the fluorophotometer and by manual computation, and the 2 calculation methods were compared.

Results—The protocol established for the 5 dogs resulted in semilogarithmic and parallel decay of corneal and aqueous humor concentrations. Manually calculated mean ± SD aqueous humor flow rates for left, right, and both eyes were 5.58 ± 2.42, 4.86 ± 2.49, and 5.22 ± 1.87 μl/min, respectively, whereas corresponding flow rates calculated by use of the automated software were 4.54 ± 3.08, 4.54 ± 3.10, and 4.54 ± 2.57 μl/min, respectively. Values for the left eye were significantly different between the 2 computation methods.

Conclusions and Clinical Relevance—Aqueous humor flow rates can be determined in dogs, using fluorophotometry. This technique can be used to assess pathologic states and medical and surgical treatments that alter aqueous humor dynamics. (Am J Vet Res 2001;62:853–858)

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in American Journal of Veterinary Research

Abstract

Objective—To evaluate effects of topical application of a 2% solution of dorzolamide on intraocular pressure (IOP) and aqueous humor flow rate in clinically normal dogs.

Animals—15 Beagles.

Procedure—The IOP was measured in both eyes of all dogs for 3 days to determine baseline values. In a single-dose study, 50 μl of dorzolamide or control solution was applied in both eyes at 7:00 AM, and IOP was measured 7 times/d. In a multiple-dose study, dorzolamide or control solution was applied to both eyes 3 times/d for 6 days, and IOP was measured 4 times/d during treatment and for 5 days after cessation of treatment. Aqueous humor flow rate was measured for all dogs fluorophotometrically prior to treatment and during the multiple-dose study.

Results—In the single-dose study, dorzolamide significantly decreased IOP from 30 minutes to 6 hours after treatment. Mean decrease in IOP during this time span was 3.1 mm Hg (18.2%). Maximal decrease was detected 6 hours after treatment (3.8 mm Hg, 22.5%). In the multiple-dose study, dorzolamide decreased IOP at all time points, and maximal decrease was detected 3 hours after treatment (4.1 mm Hg, 24.3%). Mean aqueous humor flow rate decreased from 5.9 to 3.4 μl/min (43%) after treatment in the dorzolamide group.

Conclusions and Clinical Relevance—Topical application of a 2% solution of dorzolamide significantly decreases IOP and aqueous humor flow rate in clinically normal dogs. Therefore, topical administration of dorzolamide should be considered for the medical management of dogs with glaucoma. (Am J Vet Res 2001;62:859–863)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine effects of commonly used ophthalmic antibiotics on cellular morphologic characteristics and migration of canine corneal epithelium in cell culture.

Sample Population—Corneal epithelial cells harvested from corneas of 12 euthanatized dogs and propagated in cell culture.

Procedure—Cells were treated with various antibiotics after a defect was created in the monolayer. Cellular morphologic characteristics and closure of the defect were compared between antibiotic-treated and control cells.

Results—Cells treated with ciprofloxacin and cefazolin had the greatest degree of rounding, shrinkage, and detachment from plates. Cells treated with neomycin-polymyxin B-gramicidin and gentamicin sulfate had rounding and shrinkage but with less detachment. Cells treated with tobramycin and chloramphenicol grew similarly to control cells. On the basis of comparisons of defect circumference between control cells and cells exposed to antibiotics, tobramycin affected cellular migration the least.

Conclusion and Clinical Relevance—Effects of ciprofloxacin and cefazolin on morphologic characteristics of canine corneal epithelial cells in vitro should be taken into consideration before using these antibiotics for first-line of treatment for noninfected ulcers. Of the antibiotics tested that have a primarily gramnegative spectrum of coverage, gentamicin inhibited corneal epithelial cell migration and had greater cytopathologic effects than tobramycin did. For antibiotics with a gram-positive coverage, chloramphenicol had no cytopathologic effects on cells in comparison to cefazolin, which caused most of the cells to shrink and detach from the plate. Polymyxin B-neomycingramicidin was midrange in its effects on cellular morphologic characteristics and migration. (Am J Vet Res 2001;62:xxx–xxx)

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in American Journal of Veterinary Research

Abstract

Objective—To determine ocular tissue drug concentrations after topical ocular administration of 0.3% ciprofloxacin and 0.5% moxifloxacin in ophthalmologically normal horses.

Animals—24 ophthalmologically normal adult horses.

Procedures—0.3% ciprofloxacin and 0.5% moxifloxacin solutions (0.1 mL) were applied to the ventral conjunctival fornix of 1 eye in each horse as follows: group 1 (n = 8) at 0, 2, 4, and 6 hours; group 2 (8) at 0, 2, 4, 6, and 10 hours; and group 3 (8) at 0, 2, 4, 6, 10, and 14 hours. Tears, cornea, and aqueous humor (AH) were collected at 8, 14, and 18 hours for groups 1, 2, and 3, respectively. Drug concentrations were determined via high-performance liquid chromatography.

Results—Median (25th to 75th percentile) concentrations of ciprofloxacin for groups 1, 2, and 3 in tears (μg/mL) were 53.7 (25.5 to 88.8), 48.5 (19.7 to 74.7), and 24.4 (15.4 to 67.1), respectively; in corneal tissue (μg/g) were 0.95 (0.60 to 1.02), 0.37 (0.32 to 0.47), and 0.48 (0.34 to 0.95), respectively; and in AH were lower than the limit of quantification in all groups. Concentrations of moxifloxacin for groups 1, 2, and 3 in tears (μg/mL) were 188.7 (44.5 to 669.2), 107.4 (41.7 to 296.5), and 178.1 (70.1 to 400.6), respectively; in corneal tissue (μg/g) were 1.84 (1.44 to 2.11), 0.78 (0.55 to 0.98), and 0.77 (0.65 to 0.97), respectively; and in AH (μg/mL) were 0.06 (0.04 to 0.08), 0.03 (0.02 to 0.05), and 0.02 (0.01 to 0.04), respectively. Corneal moxifloxacin concentrations were significantly higher in group 1 than groups 2 and 3.

Conclusions and Clinical Relevance—After topical ocular administration, fluoroquinolones can reach therapeutic concentrations in tears and corneal tissue of horses, even when there is an intact epithelium.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To compare prevalence of organisms and histologic changes in eyes from dogs with blastomycosis that were either untreated or undergoing treatment with itraconazole.

Design—Retrospective study.

Animals—36 dogs with endophthalmitis associated with blastomycosis.

Procedure—Signalment, results of ophthalmic examination, and duration of treatment with itraconazole were extracted from medical records. Histologic sections from eyes were examined for prevalence and viability (ie, budding) of fungal organisms. A scoring system was devised to assess the degree of inflammation.

Results—Clinically, all eyes were blind and had signs of severe endophthalmitis. Histologically, the type and degree of inflammation and prevalence of Blastomyces dermatitidis were not significantly different between dogs treated with itraconazole and untreated dogs or among groups of dogs treated for different time periods (4 to 14, 15 to 28, or 29 to 72 days). Replication of the organisms in vascular tissues as well as avascular spaces in the eyes was similar in treated and untreated dogs. Lens rupture was seen in 12 of 29 (41%) eyes.

Conclusions and Clinical Relevance—Persistence of inflammation in eyes of dogs with naturally occurring blastomycosis is likely attributable to the continued presence of B dermatitidis, regardless of the duration of treatment with itraconazole. Lens capsule rupture, a common and previously unreported histologic finding, may contribute to cataract formation and continued inflammation. (J Am Vet Med Assoc 2004; 224:1317–1322)

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in Journal of the American Veterinary Medical Association