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Biomedical subjects

Richard R Dubielzig

Publications and source records attributed to Richard R Dubielzig.

At least 19 recordsLinked to original sources
PubMed2007

Use of capecitabine to prevent acute renal allograft rejection in dog erythrocyte antigen-mismatched mongrel dogs.

OBJECTIVE: To assess efficacy and toxicity of a capecitabine (CAP)-based regimen for preventing rejection of renal allografts in dog erythrocyte antigen (DEA)-mismatched mongrel dogs. STUDY DESIGN: Prospective, pilot study. ANIMALS: Eight healthy, unrelated, DEA mismatched, adult mongrel dogs. METHODS: All dogs received CAP, starting at 50 mg/m2 PO b.i.d. 4 days preoperatively, increasing to 200 mg/m2 PO b.i.d. by the day of surgery. All dogs received cyclosporine-A (CsA) and prednisolone starting 2 days preoperatively. Standard heterotopic renal transplantation with native nephrectomy was performed. After 90 days, surviving dogs were euthanatized and histopathologic examination was performed. RESULTS: Two of 8 dogs developed acute neurotoxicity leading to death or euthanasia within 5 days of surgery. For the 6 remaining dogs, there were no statistically significant changes in complete blood count or serum biochemical values. No opportunistic infections developed during the study period. Five of 6 dogs had no to minimal evidence of graft rejection. Two of 6 dogs developed superficial and pigmentary keratitis. Significant histopathologic findings in all dogs included mild lymphoplasmacytic gastroenteritis, steroid hepatopathy, and corneal epithelial thinning. One dog had moderate interstitial nephritis and pyelitis. CONCLUSIONS: In this experimental model, a CAP-CsA-prednisolone immunosuppressive regimen was effective in preventing rejection of allografts in DEA-mismatched dogs. Severe, unpredictable neurotoxicity and variable ocular toxicity significantly limit clinical applications at this time. CLINICAL RELEVANCE: A CAP-CsA-prednisolone protocol is an effective, oral immunosuppressive regimen for prevention of allograft rejection in DEA-mismatched mongrel dogs. For clinical application, identification of patients susceptible to toxic side effects would be necessary.

Administration, Oral↗
PubMed2006

Comparison of results of computed tomography and radiography with histopathologic findings in tracheobronchial lymph nodes in dogs with primary lung tumors: 14 cases (1999-2002).

OBJECTIVE: To compare results of computed tomography (CT) and radiography with histopathologic findings in tracheobronchial lymph nodes (TBLNs) in dogs with primary lung tumors. DESIGN: Retrospective case series. ANIMALS: 14 client-owned dogs. PROCEDURES: Criteria for inclusion were diagnosis of primary lung tumor, use of thoracic radiography and CT, and histologic confirmation of TBLN status. Medical records were reviewed for signalment; history; and physical examination, clinicopathologic, radiographic, CT, surgical, and histopathologic findings. RESULTS: Tracheobronchial lymphadenopathy was not identified via radiography in any dogs. Tracheobronchial lymphadenopathy was diagnosed in 5 dogs via CT. Six dogs had histologic confirmation of metastasis to TBLNs. Radiographic diagnosis yielded 6 false-negative and no false-positive results for tracheobronchial lymphadenopathy. Computed tomography yielded 1 false-negative and no false-positive results. Sensitivity of CT for correctly assessing TBLN status was 83%, and specificity was 100%. Positive predictive value was 100%, and negative predictive value was 89%. Dogs with lymphadenopathy via CT, histologic confirmation of TBLN metastasis, or primary tumors with a histologic grade > 1 had significantly shorter survival times than their counterparts. CONCLUSIONS AND CLINICAL RELEVANCE: Results of CT evaluation of TBLN status were in agreement with histopathologic findings and more accurate than use of thoracic radiography for evaluating TBLNs in dogs with primary lung tumors. Computed tomography imaging should be considered as part of the staging process to more accurately assess the TBLNs in dogs with primary lung tumors.

Animals↗
PubMed2006

Prevention of bacterial colonization of contact lenses with covalently attached selenium and effects on the rabbit cornea.

PURPOSE: Although silicone hydrogel materials have produced many corneal health benefits to patients wearing contact lenses, bacteria that cause acute red eye or corneal ulcers are still a concern. A coating that inhibits bacterial colonization while not adversely affecting the cornea should improve the safety of contact lens wear. A covalent selenium (Se) coating on contact lenses was evaluated for safety using rabbits and prevention of bacterial colonization of the contact lenses in vitro. METHODS: Contact lenses coated with Se were worn on an extended-wear schedule for up to 2 months by 10 New Zealand White rabbits. Corneal health was evaluated with slit-lamp biomicroscopy, pachymetry, electron microscopy, and histology. Lenses worn by the rabbits were analyzed for protein and lipid deposits. In addition, the ability of Se to block bacterial colonization was tested in vitro by incubating lenses in a Pseudomonas aeruginosa broth followed by scanning electron microscopy of the contact lens surface. RESULTS: The covalent Se coating decreased bacterial colonization in vitro while not adversely affecting the corneal health of rabbits in vivo. The Se coating produced no noticeable negative effects as observed with slit-lamp biomicroscopy, pachymetry, electron microscopy, and histology. The Se coating did not affect protein or lipid deposition on the contact lenses. CONCLUSION: The data from this pilot study suggest that a Se coating on contact lenses might reduce acute red eye and bacterial ulceration because of an inhibition of bacterial colonization. In addition, our safety tests suggest that this positive effect can be produced without an adverse effect on corneal health.

Animals↗
PubMed2005

Putative aqueous humor misdirection syndrome as a cause of glaucoma in cats: 32 cases (1997-2003).

OBJECTIVE: To characterize the clinical and morphologic aspects of aqueous humor misdirection syndrome (AHMS) in cats and provide a hypothesis regarding its pathogenesis on the basis of detailed analysis of affected cats. DESIGN: Retrospective study. ANIMALS: 32 cats (40 eyes). PROCEDURE: Medical records of cats in which AHMS was diagnosed from July 1997 to August 2003 were reviewed. In certain cats, results of additional diagnostic testing were also obtained, including A-scan, B-scan, and high-resolution ultrasonography; streak retinoscopy; video keratometry; and infrared neutralizing videoretinoscopy as well as results of analysis of flash-frozen sections and histologic examination of enucleated globes. RESULTS: Cats had a uniformly shallow anterior chamber, intact lens zonules, and a narrowed approach to an open iridocorneal angle. Mean age of affected cats was 11.7 years (range, 4 to 16 years), and female cats were significantly more often affected than male cats. Clinical signs included mydriasis, decreased pupillary light reflex, decreased menace response, and blindness. Glaucomatous changes to the optic nerve, incipient cataracts, and eventual blindness were seen. Intraocular pressure was > or = 20 mm Hg (range, 12 to 58 mm Hg) in 32 of 40 eyes. Ultrasonography and histologic examination revealed a thickened anterior vitreal face interposed between the lens and ciliary body, partial ciliary cleft collapse, and cavitated vitreal regions. Various treatment modalities were used. CONCLUSIONS AND CLINICAL RELEVANCE: AHMS affects older cats, especially females, and may result in glaucoma, vision loss, and signs of ocular pain. Topical administration of carbonic anhydrase inhibitors decreased intraocular pressure.

Age Factors↗
PubMed2005

Systemic administration of an attenuated, tumor-targeting Salmonella typhimurium to dogs with spontaneous neoplasia: phase I evaluation.

PURPOSE: Genetically modified bacteria are a potentially powerful anticancer therapy due to their tumor targeting capacity, inherent antitumor activity, and ability to serve as efficient vectors for gene delivery. This study sought to characterize the acute and short-term toxicities and tumor colonization rates of a genetically modified Salmonella typhimurium (VNP20009) in dogs with spontaneous tumors, in the context of a phase I dose escalation trial. EXPERIMENTAL DESIGN: Forty-one pet dogs with a variety of malignant tumors received weekly or biweekly i.v. infusions of VNP20009, at doses ranging from 1.5 x 10(5) to 1 x 10(8) cfu/kg. Vital signs and clinicopathologic variables were monitored regularly. Incisional biopsies were obtained before and 1 week following the first infusion for histopathology and bacterial culture. RESULTS: The nominal maximum tolerated dose was 3 x 10(7) cfu/kg, with refractory fever and vomiting being the dose-limiting toxicities. One treatment-related acute death occurred. Bacteria were cultured from tumor tissue in 42% of cases. Thirty-five patients were evaluable for antitumor response. Major antitumor responses were seen in 15% (4 complete response and 2 partial response), and disease stabilization for at least 6 weeks in 10%. CONCLUSIONS: Administration of VNP20009 at doses with acceptable toxicity results in detectable bacterial colonization of tumor tissue and significant antitumor activity in tumor-bearing dogs.

Animals↗
PubMed2005

Spontaneous uveal amelanotic melanoma in transgenic Tyr-RAS+ Ink4a/Arf-/- mice.

OBJECTIVE: To characterize a murine model of spontaneous amelanotic melanoma arising in the uvea of transgenic mice bearing a targeted deletion of the Ink4a/Arf tumor suppressor locus (exons 2 and 3) and expressing human H-ras controlled by the human tyrosinase promoter. METHODS: Ocular lesions developed in 20 (15.7%) of 127 male albino Tyr-RAS+ Ink4a/Arf-/- transgenic FVB/N mice within 6 months, and were evaluated histologically and ultrastructurally. RESULTS: Uveal melanomas were locally invasive but confined to the eye, with no evidence of metastasis. Tumor cells exhibited epithelioid and spindle-shaped morphological features and closely resembled the human counterpart. Melan-A, S100 and neuron-specific enolase expression were detected immunohistochemically. Melanosomal structures were detected using electron microscopy. The retinal pigment epithelium was intact above small melanomas, and electron microscopy of the tumors failed to show the presence of basement membrane formation or desmosomes. CONCLUSION: Spontaneous uveal malignant melanomas occurring in male Tyr-RAS+ Ink4a/Arf-/- transgenic mice arise within the choroid or ciliary body and share histopathological features characteristic of human uveal melanoma. CLINICAL RELEVANCE: Uveal melanoma research has benefited from xenograft models, but engineered mouse models of spontaneous uveal amelanotic melanoma will undoubtedly further our understanding of the genetic underpinning for this disease.

Animals↗
PubMed2005

Bilateral maxillary periodontal ligament hamartoma in a dog.

A 12.5-year-old dog was presented for severe periodontal disease and bilateral maxillary enlargement. Radiographs of the maxilla showedgeneralized root resorption, ankylosis, and rarefaction of bone with focal radiodense areas. Surgical tooth extraction of multiple maxillary teeth and bilateral incisional biopsies of the periodontal tissue and maxilla in the region of the maxillary fourth premolars were performed. Histopathologic examination showed features typical of fully differentiated periodontal ligament with abundant cementum/alveolar lining bone and sparce odontogenic epithelial cell rests. Histopathology in conjunction with radiographic and clinical signs suggested a diagnosis of bilateral periodontal ligament hamartoma. Examination 3-months postoperatively indicated uncomplicated healing of the extraction and biopsy sites with no resolution of the maxillary enlargement.

Animals↗
PubMed2004

James Wardrop and equine recurrent uveitis.

James Wardrop should be remembered not only as one of the founders of ocular pathology but also for his contributions to the field of comparative ophthalmology. He described a "specific inflammation" that veterinarians today know as equine recurrent uveitis. As described by Wardrop in the 19th century, this condition is known today to eventually lead to blindness.

Animals↗
PubMed2004

Evaluation of glutamate loss from damaged retinal cells of dogs with primary glaucoma.

OBJECTIVE: To determine whether retinal damage in dogs with primary glaucoma (PG) is consistent with ischemia-induced glutamate toxicosis. SAMPLE POPULATION: Retinal tissue sections from 25 dogs with PG and 12 normotensive control dogs. PROCEDURE: Retinal sections from control and glaucomatous dogs were stained for morphometric and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) analyses to determine whether retinal damage was consistent with glutamate toxicosis. Immunohistochemical analysis was performed to detect ischemia-like loss of glutamate from neurons in damaged areas. RESULTS: In severely damaged glaucomatous retinas, all neurosensory layers had focal regions that were thin or disrupted. There was less thinning of the outer nuclear layer (ONL) and inner nuclear layer (INL) in moderately damaged retinas than in severely damaged retinas. Acute signs of damage in the INL included cells with dark, condensed chromatin and lightly stained cytoplasm interspersed with a few TUNEL-positive cells, which was consistent with glutamate toxicosis. Glutamate immunoreactivity was reduced in thin areas and in damaged cells of the INL and ONL, which was consistent with glutamate release in damaged areas. Glutamate immunoreactivity was increased in putative Müller cells in damaged areas, which also was consistent with glutamate release. CONCLUSIONS AND CLINICAL RELEVANCE: Retinal damage in dogs with PG differs in intensity in focal areas. Damage in affected regions resembles damage induced by glutamate. Glutamate is lost from damaged neurons and accumulates in Müller cells, which is consistent with increased glutamate release contributing to the damage. Glutamate antagonists may protect INL cells in dogs with glaucoma.

Analysis of Variance↗
PubMed2003

Primary ocular osteosarcoma in a dog.

An adult male Rottweiler presented to the veterinary medical teaching hospital at Purdue University with a 1-month history of hyphema. On physical examination conjunctivitis, episcleral hyperemia, corneal edema, hyphema, mild glaucoma and loss of vision were observed in the left eye. No other abnormalities were found. The left globe was surgically removed because of the high likelihood of neoplasia and it was fixed in 10% buffered formalin and submitted for pathology. A histologic diagnosis of primary osteosarcoma of the eye was made. Radiographic evaluation did not reveal any evidence of other tumors or pulmonary metastasis. This is the fourth canine case of primary intraocular osteosarcoma to be documented.

Animals↗
PubMed2003

A study of the morphology of canine eyes enucleated or eviscerated due to complications following phacoemulsification.

This study was undertaken to describe the histopathologic abnormalities observed in canine eyes enucleated or eviscerated due to complications following phacoemulsification; to correlate these findings with the clinical abnormalities reported, and to suggest, if apparent, likely causes and effects of these abnormalities. Sixty-six canine globes or evisceration samples received for histopathologic interpretation over a 10-year period (1990-2000) were studied. All globes and evisceration samples were obtained from clinical patients examined by board-certified ophthalmologists. Hematoxylin and eosin (H&E) and alcian blue/periodic acid Schiff (PAS) stained sections were examined by light microscopy in every case. A tissue Gram stain was used when indicated. Clinical information obtained from the pathology submission form was reviewed in all cases, and obtained from questionnaires completed and returned by an ophthalmologist for 51 cases (77%). The most frequent histopathologic diagnoses were glaucoma (76%) and retinal detachment (64%). The most frequently reported clinical abnormalities in this series were glaucoma (86%) and uveitis (82%). Five problem areas were identified that appear to make a significant contribution to the failure of canine cataract surgery and merit further investigation: pre-iridal fibrovascular membranes; lens fiber regrowth; lens epithelial membranes; endophthalmitis, and the health of the corneal surgical incision.

Animals↗
PubMed2002

Morphologic features of degeneration and cell death in the neurosensory retina in dogs with primary angle-closure glaucoma.

OBJECTIVE: To investigate cellular death in the neurosensory portion of the retina during the first 7 days after onset of clinical signs of overt primary angleclosure glaucoma (PACG) in dogs. SAMPLE POPULATION: 14 globes from dogs with PACG and 2 normotensive globes from dogs with PACG in the opposite eye. PROCEDURES: Retinas were examined via light microscopy and terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick end-labeling. RESULTS: Necrosis of ganglion cells and segmental degeneration of the nerve fiber layer rapidly progressed to scattered full-thickness retinal attenuation and disorganization. Apoptosis was detectable within 1 day after onset of PACG and was prominent by 3 days. Necrosis of ganglion cells was significantly greater in retinas affected for < or = 1 day, compared with retinas affected for > 1 day. In contrast, apoptosis in the ganglion cell layer was significantly greater in retinas affected for > 1 day, compared with retinas affected for < or = 1 day. End-stage retinal atrophy was seen by day 7. CONCLUSIONS AND CLINICAL RELEVANCE: The presence of necrotic ganglion cells within 1 day after onset of clinical signs suggests a narrow window of opportunity to initiate effective therapy in overt PACG. Photoreceptor death is an important and striking aspect of neurosensory retinal degeneration after acute onset of PACG.

Animals↗
PubMedDate not supplied

Canine lobular orbital adenoma: a report of 15 cases with distinctive features.

OBJECTIVE: To describe a unique orbital neoplasm in dogs, of lacrimal or salivary gland origin. ANIMALS STUDIED: Fifteen dogs with lesions consistent with a diagnosis of lobular adenomas involving the orbit were identified from the Comparative Ophthalmic Pathology Laboratory of Wisconsin from 1994 to 2001. RESULTS: The neoplasm occurred in nine females and six males. Affected dogs ranged in age from 7 to 17 years (mean = 9.7 years). Follow-up information was available for 13 of the 15 cases. The clinical presentation included swollen/hyperemic eyelids (4/15), third eyelid protrusion (3/15), conjunctival mass (6/15), exophthalmos (4/15), resistance to retropulsion (2/15), or strabismus (1/15). In 13 cases the masses were composed of nodular, friable tissue and they were solid in two cases. Histologically, the tissue was found in encapsulated lobules resembling well differentiated lacrimal or salivary glands but completely lacking ducts. Granular PAS-positive material was found within the cytoplasm. There was recurrence in 10 of the 13 cases available for follow-up. Of those cases in which enucleation or exenteration was performed (3/15), there was recurrence of disease in one case. In three cases the dogs were euthanized before recurrence at 3 months, 5 months and 3 years post surgery. None of the deaths was related to the tumor. CONCLUSION: In the 15 cases reviewed, lobular adenomas of the orbit presented clinically and histologically as a benign neoplasm of lacrimal or salivary gland origin. Recurrence was likely unless the mass was completely excised, at times requiring orbital exenteration.

Adenoma↗
PubMedDate not supplied

A morphologic study of intravitreal membranes associated with intraocular hemorrhage in the dog.

Abstract We aimed to characterize intravitreal membranes in dogs and determine, if possible, associated predisposing conditions. Five globes in which intravitreal membranes were identified were evaluated. These originated from four Labrador Retrievers or Labrador-cross dogs and a Springer Spaniel. The ages of the dogs ranged from 4 to 11 years. Standard histology and immunohistochemical procedures for factor VIII-related antigen, smooth muscle actin (SMA), vimentin and glial fibrillary acidic protein (GFAP) were performed. Intravitreal membranes varied from loosely to highly organized. The extent of organization corresponded with increasing immunoreactivity for vimentin and GFAP, indicating their predominantly glial origin. They were never immunopositive for smooth muscle actin, nor were they vascularized. In all cases, they were associated with intravitreal hemorrhage. Additional common findings included epiretinal membranes, retinal neovascularization, preiridal fibrovascular membranes and glaucoma. Intravitreal membranes may be a sequelae of intravitreal hemorrhage. This in turn, may arise from new vessels associated with epiretinal or preiridial membranes, or hemorrhage associated with optic disc cupping or retinal neovascularization. All of these phenomena may accompany glaucoma.

Animals↗
PubMedDate not supplied

Light-microscopy evaluation of zonular fiber morphology in dogs with glaucoma: secondary to lens displacement.

Lens displacement resulting in secondary glaucoma is common in terrier breeds. This study was carried out to evaluate whether light microscopy was useful in detecting abnormal patterns in zonular fiber protein. Eyes from 63 dogs with glaucoma secondary to lens displacement were evaluated for the presence of abnormal zonular fiber morphology using the following stains: hematoxylin and eosin, periodic acid Schiff (PAS), Masson's trichrome and Verhoeff's elastin stains. Two distinct forms of abnormal zonular fiber morphology were recognized and designated as zonular fiber dysplasia (ZFD) and zonular fiber collagenization (ZFC). ZFD protein morphology was characterized by being tightly adherent to the nonpigmented ciliary body epithelium, exhibiting a distinct lamellar and cross-hatched pattern and staining strongly positive with PAS and trichrome stains, and staining negative with elastin stains. ZFD was predominant in terrier breeds (18 of 29) and Shar-Pei dogs (4 of 29). ZFC abnormality was characterized by excessive zonular fiber that was not tightly adherent to the ciliary body epithelium and staining positive with PAS, trichrome (blue for collagen) and elastin stains. Only 7 of 19 dogs with ZFC changes were terrier breeds, and there was no pattern in the breeds affected. Fifteen of the 63 dogs used in the study had normal appearing zonular fibers. The staining pattern in these dogs matched normal controls by staining positive with PAS and Verhoeff's elastin stains and had only minimal positive staining with Masson's trichrome stain. Results suggest that light microscopy is useful in detecting breed-related changes in zonular fiber morphology in cases of glaucoma secondary to lens displacement. These changes may correlate with the presence of abnormal zonular fiber proteins and might be important in the pathogenesis of primary lens displacement in terrier and Shar-Pei dogs.

Animals↗
PubMedDate not supplied

Canine ocular onchocerciasis in the United States: two new cases and a review of the literature.

Since 1991, 53 cases of canine ocular onchocerciasis have been reported in the literature worldwide, 43 of these were from Greece, five from Hungary, and five from the western United States. Information on the histopathologic features of canine ocular onchocerciasis is limited. We describe the histopathologic features of canine ocular onchocerciasis in two dogs from California that presented clinically with firm episcleral nodules and uveitis unilaterally. Pertinent literature and pathogenesis are reviewed; recognizable clinical features and treatment are discussed. The cases presented were diagnosed via histopathology of the enucleated globes and episcleral granulomas at the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW). Positive identification of adult Onchocerca within episcleral granulomas was made based on light-microscopy features. Histopathologic examination of both globes revealed episcleral parasites surrounded by granulomas containing few to moderate numbers of eosinophils. Other sequelae, in both cases, included lymphoplasmacytic uveitis, preiridal fibrovascular membranes, peripheral anterior synechiae, retinal degeneration, and optic nerve head cupping. Both male and female worms were present, as were in utero microfilariae in both cases. Worms in both cases were tentatively identified as Onchocerca lienalis. Ocular onchocerciasis should be a differential consideration in cases of canine conjunctival nodules or periorbital swelling, particularly in dogs from the western United States.

Animals↗
PubMedDate not supplied

Canine goniodysgenesis-related glaucoma: a morphologic review of 100 cases looking at inflammation and pigment dispersion.

PURPOSE: To investigate the role of pigment dispersion and inflammation in the pathogenesis of goniodysgenesis-related glaucoma (GDRG). PROCEDURES: Cases of GDRG were selected when the duration of the disease was specified and there was not any confounding pathology. Cases were grouped into < or = 7-day (acute), and > 7-day (chronic) durations, based on the time required to effect end-stage retinal damage. Acute cases were further divided into < 4-day and 4-7-day groups to assess peracute changes. Slides were evaluated for four individual signs of pigment dispersion: segmental loss of posterior iris pigment epithelium, clumping of posterior iris pigment epithelium, pigmented cells in the trabecular meshwork or anterior chamber and preferential settling of pigmented cells in the ventral aspect of the iridocorneal angle. Slides were also evaluated for the presence of neutrophils and/or lymphoplasmacytic cells in the trabecular meshwork (TM). Differences between groups were analyzed statistically. RESULTS: Of 100 cases evaluated, 34 were < or = 7-days (acute) (14 < 4-day and 20 4-7-day) and 66 were > 7-days (chronic) in duration. Of all globes examined, 96% had at least one sign of pigment dispersion, with no significant difference between groups. Two or more signs of pigment dispersion were present in 76% of all globes. The 4-7-day group was significantly more likely than the < 4-day group to have at least two signs. The difference was not significant between < or = 7- and > 7-day groups. Neutrophils were present in the TM of 86% of < 4-day and 50% of 4-7-day cases. Cases in the < or = 7-day group were significantly more [corrected] likely than > 7-day cases to have neutrophils in the TM, with 65% and 17% [corrected] positive cases, respectively. Lymphoplasmacytic inflammation was present in 53% of all cases, with no significant difference between groups. Cases in the < or = 7-day group were significantly more likely than > 7-day cases to have both types of inflammation. CONCLUSIONS: Our results indicate that both acute inflammation and pigment dispersion may be key factors in the pathogenesis of GDRG. Pigment dispersion is prevalent at all time points and increases during the first 7 days. The finding of iris pigment epithelial loss supports the theory that pupillary block associated with iris-lens touching may be important in the pathogenesis of GDRG.

Animals↗