High flow nasal cannula: Influence of gas type and flow rate on airway pressure and CO2 clearance in adult nasal airway replicas.

BACKGROUND: High flow nasal cannula therapy is a form of respiratory support which delivers high flow rates of heated, humidified gas to the nares via specialized cannula. Two primary mechanisms of action attributed to the therapy are the provision of positive airway pressure as well as clearance of CO2-rich exhaled gas from the upper airways. METHODS: Physiologically accurate nose-throat airway replicas were connected at the trachea to a lung simulator, where CO2 was supplied to mimic the CO2 content in exhaled gas. Cannula delivered either air, oxygen or heliox (80/20%volume helium/oxygen) to the replicas at flow rates ranging from 0 to 60 l/min. Five replicas and three cannulas were compared. Tracheal pressure and CO2 concentration were continuously measured. The lung simulator provided breaths with tidal volume of 500 ml and frequency of 18 breaths/min. Additional clearance measurements were conducted for tidal volume and breathing frequency of 750 ml and 27 breaths/min, respectively. FINDINGS: Cannula flow rate was the dominant factor governing CO2 concentration. Average CO2 concentration decreased with increasing cannula flow rate, but above 30 L/min this effect was less pronounced. Tracheal positive end-expiratory pressure increased with flow rate and was lower for heliox than for air or oxygen. A predictive correlation was developed and used to predict positive end-expiratory pressure for a given cannula size as a function of supplied flow rate and occlusion of the nares. INTERPRETATION: Compared with administration of air or oxygen, administration of heliox is expected to result in similar CO2 clearance from the upper airway, but markedly lower airway pressure.

Local photodynamic therapy for equine squamous cell carcinoma: evaluation of a novel treatment method in a murine model.

The objective of this study was to evaluate the effect of local photodynamic therapy (PDT) with verteporfin on tumor growth inhibition of squamous cell carcinoma (SCC) in a murine model. SCC was implanted in 85 nude mice by subcutaneous injection of A-431 SCC cells. Treatment groups (10 mice/group) received an intra-tumoral injection of verteporfin dissolved in dimethyl sulfoxide (DMSO) or 5% dextrose solution at a dose of 0.01 or 0.1mg/cm3. Controls received only solvent, or no injectate. All groups received identical light illumination (100J/cm2). Relative change in tumor volume (RCTV) at day 30 was compared between groups using the Wilcoxon rank sum test (P< 0.05). Local PDT with verteporfin at a dose of 0.1mg/cm3 resulted in significantly lower RCTV at day 30 compared to controls. Choice of solvent (DMSO versus D5W) did not affect the results. Local PDT may be an effective adjunctive therapy for the treatment of periocular equine SCC.

Management of bilateral uveitis in a Toxoplasma gondii-seropositive cat with histopathologic evidence of fungal panuveitis.

A 5-year-old, neutered male Domestic Short-haired cat was referred with a 5-month history of anterior uveitis and cataract in the right eye. Clinical examination confirmed anterior uveitis and immature cataract in the right eye and chorioretinitis in the left eye. Ocular ultrasound showed a retinal detachment in the right eye. Diagnostic testing revealed elevated serum titers for Toxoplasma gondii. Anterior uveitis in the right eye and chorioretinitis in the left eye progressed, resulting in blindness despite a 21-day course of clindamycin and aggressive topical medical management of uveitis. The right eye was enucleated and histopathologic evaluation of the globe revealed panuveitis and multiple organisms morphologically consistent with Histoplasma capsulatum. Systemic treatment with itraconazole was initiated. Vision returned after 3 months of treatment and complete resolution of the retinal hemorrhages with formation of a flat chorioretinal scar was noted after 6 months of therapy. Itraconazole was discontinued 7 months after starting therapy, at which time the funduscopic appearance of the chorioretinal scar had remained static for 1 month. The cat has remained visual without evidence of disease progression for 6 months following discontinuation of itraconazole.

Xenotransplantation of cryopreserved equine squamous cell carcinoma to athymic nude and SCID mice.

Cryopreserved equine ocular squamous cell carcinoma (SCC) was inoculated subcutaneously into 15 athymic nude and 15 SCID mice. Xenotransplantation resulted in tumor growth in two athymic nude mice and 1 SCID mouse. Histological appearance and immunohistochemical characterization using cytokeratin 5/6 markers and p53 markers of the tumor grown in mice was in full accord with the original equine tumors. No evidence of metastasis was noted in any mouse. This model may serve as a relevant in vivo model for studying the biology of equine ocular SCC and for the testing of new therapeutic modalities.

Effect of cyclosporine on conjunctival mucin in a canine keratoconjunctivitis sicca model.

PURPOSE: To test the hypothesis that beneficial effects of Cyclosporin A (CsA; Sandimmune; Sandoz, Basel, Switzerland) in treating keratoconjunctivitis sicca (KCS) include an effect on the mucin-producing conjunctival goblet cells independent of CsA's effect on lacrimation. METHODS: Keratoconjunctivitis sicca was induced bilaterally in six dogs after removal of orbital and nictitans lacrimal glands. Two weeks after induction of KCS, either 2% CsA or vehicle was applied twice daily to each surgically altered eye until 6 weeks after KCS induction. Eyes of three control dogs without surgically altered eyes were treated twice daily with vehicle only. Incisional biopsy specimens of ventral fornix conjunctiva were collected before gland removal (baseline) and at 2, 4, and 6 weeks after KCS induction. At each sampling time, eyes were photographed, and color images were subsequently graded for degree of conjunctivitis and characteristics of ocular discharge. Intracellular mucin stores in conjunctival epithelia were estimated using computer-assisted morphometry of biopsy specimen cross sections, and clinical and morphometric findings were correlated. RESULTS: Lacrimal gland removal resulted in induction of KCS in dogs by 2 weeks, with mean Schirmer tear test (STT) values of 5 mm/min or less occurring in surgically altered eyes compared with STT values of 22.5 mm/min before surgery and 22.9 mm/min in unaltered control eyes at 2 weeks. In surgically altered eyes, STTs remained low during the 6-week study, independent of topical treatment. Intracellular mucin stores were quantified from conjunctival samples collected from each eye at baseline and 2, 4, and 6 weeks. At 4 and 6 weeks (after 2 and 4 weeks of topical treatment), intraepithelial mucin quantities were significantly greater (P: < 0.05) in CsA-treated KCS eyes (14.4 and 13.1 microm(2)/microm, respectively) compared with pretreatment KCS (7.4 microm(2)/microm) eyes and vehicle-treated KCS eyes (7.3 and 8.5 microm(2)/microm, respectively). KCS eyes treated with CsA had lower conjunctivitis and ocular discharge scores than did vehicle-treated KCS eyes. CONCLUSIONS: Topical 2% CsA restored in vivo conjunctival mucin stores to control levels over a 4-week period, determined by computer-assisted morphometry of sequential conjunctival biopsy specimens from eyes of dogs with surgically induced KCS. Degree of conjunctivitis and severity of mucus discharge were decreased in KCS eyes treated with CsA. Because lacrimal tissues were removed from animals in this study, conjunctival responses occurred independent of lacrimogenic effect(s). These results indicate that restoration of conjunctival goblet cell mucin production, i.e., the balance between synthesis and secretion of mucin glycoproteins, may play an important role in the beneficial effect of CsA in treating KCS.

Cyclosporine has a direct effect on the differentiation of a mucin-secreting cell line.

Cyclosporine is a potent immunosuppressant used in the treatment of ulcerative colitis and keratoconjunctivitis sicca. Neither the etiologies of these diseases nor the mechanism by which cyclosporine exerts its therapeutic effect is well understood. Since both diseases are linked by a common decrease in mucin-filled goblet cells, this study tests a hypothesis that cyclosporine acts directly on goblet cells to promote their differentiation and production of secretory mucins. The HT29-18N2 human colon adenocarcinoma cell line, which is capable of forming monolayers of well-differentiated goblet cells, was used as a model system. Cyclosporine induced a dose-dependent increase in intracellular mucin stores. A 2-week exposure to 1 microM cyclosporine resulted in an average increase in mucin volume of 94%. This increase resulted from both a higher percentage of cells with mucin stores and an increased volume of mucin per cell. PSC-833, a nonimmunosuppressive analog of cyclosporine, also increased mucin production. The intracellular accumulation of mucin was not a result of reduced secretion, since the time required for the release of pulse-radiolabeled glycoproteins was similar for both control and cyclosporine-treated monolayers. The effect of cyclosporine was not mediated by the drug's previously documented abilities to decrease cellular proliferation rates, inhibit calmodulin, antagonize prolactin receptor binding, or modulate prostaglandin production.

Equine conjunctival pseudotumors.

Five horses presented with unilateral pink, smooth, nonulcerated conjunctival masses with histologic features characteristic of inflammatory pseudotumors, i.e. proliferative inflammatory lesions clinically resembling true neoplasia. Although causes for the inflammatory lesions were not determined, based on the presence histologically of mononuclear (predominantly lymphocytic) inflammatory cell infiltrates and the absence of infectious agents, parasites or foreign bodies, an immune-mediated pathogenesis was suspected. Affected horses ranged from 5 to 8 years of age with no apparent breed or sex predilection. Conjunctival lesions were nodular in two cases and relatively flat and more diffuse in three cases. Third eyelid lesions were present in three cases and two affected eyes had corneal involvement. Based on findings from these five cases, the prognosis for equine conjunctival pseudotumors appears to be good when lesions are treated by partial or complete surgical excision, local administration of anti-inflammatory agents, or a combination of surgery and anti-inflammatory therapy.

Conjunctival malignant melanoma in a horse.

A case of malignant melanoma originating from the conjunctiva of a horse is reported. The tumor exhibited locally aggressive behavior as evidenced clinically by recurrence following two treatment episodes including surgical excision on each occasion and one application of cryotherapy. The orbit was subsequently exenterated and histologically malignant conjunctival melanoma was confirmed. Histopathologic features included variable pigmentation with amelanotic sites demonstrating marked cellular and nuclear pleomorphism with high numbers of mitotic figures. Cords of neoplastic cells invaded the sclera and cornea. Following exenteration, the horse exhibited no recurrence of the tumor for five years before being lost to follow-up. To our knowledge, this is the first report of primary malignant conjunctival melanoma in a horse.

Congenital ocular anomalies and ventricular septal defect in a dromedary camel (Camelus dromedarius).

A 5-wk-old female dromedary camel (Camelus dromedarius) was clinically diagnosed with bilateral corneal dermoids, incomplete congenital cataracts, a left persistent hyaloid artery (PHA), and a ventricular septal defect (VSD). The corneal dermoids were removed by lamellar keratectomy, and vision improved in the left eye. Thirteen months after dermoid surgery, the calf was presented for enlargement of the right eye. Glaucoma was confirmed in the right eye, and corneal fibrosis and cataract were noted in the left eye. Persistence of the VSD was confirmed by cardiac ultrasonography. The calf was euthanized, and necropsy findings confirmed VSD. Histopathologic examination revealed bilateral corneal thinning and fibrosis, cataracts with retrolental fibroplasia, and retinal dysplasia. Additional changes in the right globe were anterior segment dysgenesis, ruptured lens capsule, chronic phacoclastic uveitis, and retinal separation. The PHA was confirmed in the left eye.

Detection of feline herpesvirus 1 DNA in corneas of cats with eosinophilic keratitis or corneal sequestration.

OBJECTIVE: To determine whether feline herpesvirus 1 (FHV-1) DNA is in the corneas of clinically normal cats and cats with eosinophilic keratitis or corneal sequestration. SAMPLE POPULATION: Corneal biopsy specimens obtained from cats referred for treatment of corneal sequestration or eosinophilic keratitis. PROCEDURE: Corneal scraping or keratectomy specimens collected from clinically normal cats, cats with eosinophilic keratitis, and cats with corneal sequestration were evaluated for FHV-1 DNA by use of polymerase chain reaction (PCR). DNA was extracted from the tissue, and 1 microgram was assayed for FHV-1 by use of a single-round (40 cycles) PCR assay with primers directed at a 322-bp region of the thymidine kinase gene. Polymerase chain reaction positivity for clinically normal and affected cats of various breeds was compared by chi 2 analysis at alpha = 0.05. RESULTS: The FHV-1 DNA was detected in 5.9% (1/17) of corneas from clinically normal cats, in 55.1% (86/156) of corneal sequestra, and in 76.3% (45/59) of scraping specimens from cats with eosinophilic keratitis. Prevalence was significantly (P < 0.001) greater for cats with corneal sequestration or eosinophilic keratitis than for clinically normal cats. For cats with corneal sequestration, prevalence of FHV-1 DNA was significantly lower in Persian and Himalayan, compared with domestic shorthair and longhair breeds. CONCLUSION: Data strongly imply involvement of FHV-1 in the pathogenesis of eosinophilic keratitis and corneal sequestration. In Persian and Himalayan breeds, however, other nonviral factors also appear to be involved. CLINICAL RELEVANCE: Feline herpesvirus 1 must be considered when treating cats with corneal sequestration or eosinophilic keratitis.

Presumed lipid retinopathy in a diabetic dog.

An eight-year-old neutered male diabetic Cardigan Welsh Corgi was presented for bilateral mature cataracts. Phacoemulsification and intraocular lens implantation were performed routinely, and recovery was uneventful for several months except for lipemic aqueous flare which gradually resolved during the postoperative period. Five months following surgery the owner presented the dog for decreased vision. White retinal deposits were visualized ophthalmoscopically. Serum analysis revealed that the dog was concurrently markedly hyperlipemic. The patient's diet was changed from a high- to a low-fat diet, following which diabetes control improved, hyperlipemia resolved, and the retinal deposits decreased markedly in size. The retinal deposits seen ophthalmoscopically are presumed to be lipid based upon their association with marked hyperlipemia, and the concurrent resolution of hyperlipemia and the fundic lesions.

Surgery of the adnexa.

Review of the functional anatomy of ocular adnexal tissues is followed by presentation of surgical procedures aimed at correcting conditions of the eyelids, conjunctiva, and third eyelids of small animals. Procedures used effectively by the primary author are described in detail including instances where combination procedures may be indicated. Some newer, recently described techniques are also briefly discussed. Illustrations of applied anatomy and multiple surgical techniques are provided by illustrator and coauthor Dr. Gheorghe Constantinescu. References are given to encourage readers to further explore alternative techniques focusing on the surgical correction of adnexal diseases of dogs and cats.

Eyelid and nasolacrimal disease.

An understanding of normal structure and function of the equine eyelid is essential to make an accurate diagnosis and appropriately treat equine eyelid diseases. Entropion, eyelid trauma, neoplasia, and nasolacrimal disorders are reviewed. Methods of diagnosis and treatment are presented.

Immunotherapy of periocular squamous cell carcinoma with metastasis in a pony.

A 5-year-old Pony of America mare was referred for evaluation of inflamed upper and lower right eyelids. Squamous cell carcinoma of the eyelids and ulcerative keratitis secondary to self-trauma were diagnosed. Initial treatment of the eyelid neoplasia with 2 applications of cryotherapy failed to resolve the lesions, and immunotherapy with bacillus of Calmette-Guerin (BCG) was instituted. Multiple injections of BCG over a 17-week period resulted in progressive shrinkage of the tumor mass, but regional metastasis to the ipsilateral submandibular lymph node occurred. Six months later, ocular neoplastic lesions were not evident, and the lymph node had regressed in size. Eighteen months after the diagnosis of metastatic disease, signs of recurrence were not noticed in either the primary or secondary tumor sites. Squamous cell carcinoma of the equine eyelid historically carries a poor prognosis for resolution. Immunotherapy for equine ocular squamous cell carcinoma should be considered as a treatment alternative to cryosurgery, radiotherapy, hyperthermy, and CO2 laser ablation, especially in cases involving the eyelid.

Comparison of serum and plasma taurine values in Bengal tigers with values in taurine-sufficient and -deficient domestic cats.

A white Bengal tiger was determined to have a central retinal lesion and a central visual defect. Because of the known association between feline central retinal degeneration (CRD) and taurine deficiency in domestic cats, plasma concentrations of taurine were measured in this tiger. Serum concentrations of taurine, methionine, and cystine also were measured in white Bengal tigers, orange Bengal tigers, taurine-sufficient domestic cats, and taurine-deprived and tissue-taurine-depleted visually impaired cats with CRD. Hepatic and brain enzymes responsible for taurine synthesis were identified in tissue specimens from an orange Bengal tiger. Serum taurine concentrations were lower in white vs orange tigers, but were not as low as those in cats with CRD. Thus, we concluded that taurine depletion did not account for the central retinal lesion in the white Bengal tiger.

Hemorrhage from the cosmetic otoplasty of Doberman Pinschers with von Willebrand's disease.

The hemorrhagic tendencies of 23 Doberman Pinscher pups were observed during cosmetic otoplasty and were ranked by a +1 to +4 grading system (+1 = least hemorrhage, and +4 = most hemorrhage). A second estimate of the hemostatic competencies of these dogs was made by counting the gauze sponges used in the otoplasties. Factor VIII-related antigen concentrations and coagglutinin cofactor concentrations were measured in plasma samples from blood drawn not more than 30 hours before the surgical procedures were done. The factor VIII-related antigen concentrations were between 9% and 147% of the concentration in a normal plasma pool, and the coagglutinin cofactor concentrations were between 1% and 165%, indicating that some of these dogs had von Willebrand's disease. The hemorrhagic tendencies of 12 pups were graded +1. This group had a mean antigen concentration of 75% (min-max, 38% to 147%) and a mean coagglutinin cofactor concentration of 89% (min-max, 42% to 165%). These were significantly greater than the antigen and cofactor concentrations of the grades +2 (n = 5), +3 (n = 3), or +4 (n = 3) dogs. Significant differences were not found when antigen concentrations of the grade +2 dogs (mean, 16%; min-max, 11% to 22%), grade +3 dogs (mean, 13%; 12% to 16%), and grade +4 dogs (mean, 11%; 9% to 12%) were compared with each other, nor were significant differences seen among the coagglutinin cofactor concentrations of the grade +2 dogs (mean, 7%; min-max, 1% to 11%), grade +3 dogs (mean, 6%, 4% to 8%), and grade +4 dogs (mean, 5%; 2% to 9%).(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrasonographic demonstration of popliteal cysts in rheumatoid arthritis. A noninvasive technique.

Ultrasound scanning techniques detected popliteal cysts in 14 of 24 knees affected with rheumatoid arthritis and associated with an anterior effusion. Serial scans demonstrated the persistence of cysts when effusion was not controlled by intraarticular steroid and lidocaine, and regression of cyst following control of effusion with anterior synovectomy. As the technique is noninvasive, painless, and reproducible, ultrasound scanning should be the technique of choice for the detection and assessment of popliteal cysts.