Michael G. Davidson

Guidelines for the Identification, Evaluation, and Management of Systemic Hypertension in Dogs and Cats

Consensus Statements of the American College of Veterinary Internal Medicine (ACVIM) provide veterinarians with guidelines regarding the pathophysiology, diagnosis, or treatment of animal diseases. The foundation of the Consensus Statement is evidence-based medicine, but if such evidence is conflicting or lacking, the panel provides interpretive recommendations on the basis of their collective expertise. The Consensus Statement is intended to be a guide for veterinarians, but it is not a statement of standard of care or a substitute for clinical judgment. Topics of statements and panel members to draft the statements are selected by the Board of Regents with input from the general membership. A draft prepared and input from Diplomates is solicited at the ACVIM Forum and via the ACVIM Web site and incorporated in a final version. This Consensus Statement was approved by the Board of Regents of the ACVIM before publication.

Clinicopathological abnormalities and treatment response in 24 dogs seroreactive to Bartonella vinsonii (berkhoffii) antigens.

Bartonella vinsonii (B. vinsonii) subspecies berkhoffii is a recently recognized cause of endocarditis, myocarditis, and granulomatous disease in dogs. In an effort to elucidate other potential disease manifestations, the case records of 24 dogs that were seroreactive to B. vinsonii (berkhoffii) antigens were studied retrospectively. Diagnoses included immune-mediated hemolytic anemia, neutrophilic or granulomatous meningoencephalitis, neutrophilic polyarthritis, cutaneous vasculitis, and uveitis. Repeated B. vinsonii (berkhoffii) antibody titers became negative after treatment. This study indicates that a diverse spectrum of disease manifestations and clinicopathological abnormalities can be detected in dogs that are seroreactive to B. vinsonii (berkhoffii) antigens.

Efficacy of Doxycycline, Azithromycin, or Trovafloxacin for Treatment of Experimental Rocky Mountain Spotted Fever in Dogs

ABSTRACT Dogs were experimentally inoculated with Rickettsia rickettsii (canine origin) in order to compare the efficacies of azithromycin and trovafloxacin to that of the current antibiotic standard, doxycycline, for the treatment of Rocky Mountain spotted fever. Clinicopathologic parameters, isolation of rickettsiae in tissue culture, and PCR amplification of rickettsial DNA were used to evaluate the response to therapy or duration of illness (untreated infection control group) in the four groups. Concentrations of the three antibiotics in plasma and blood cells were measured by high-performance liquid chromatography. Doxycycline and trovafloxacin treatments resulted in more-rapid defervescence, whereas all three antibiotics caused rapid improvement in attitudinal scores, blood platelet numbers, and the albumin/total-protein ratio. Based upon detection of retinal vascular lesions by fluorescein angiography, trovafloxacin and doxycycline substantially decreased rickettsia-induced vascular injury to the eye, whereas the number of ocular lesions in the azithromycin group did not differ from that in the infection control group. As assessed by tissue culture isolation, doxycycline resulted in the earliest apparent clearance of viable circulating rickettsiae; however, rickettsial DNA could still be detected in the blood of some dogs from all four groups on day 21 postinfection, despite our inability to isolate viable rickettsiae at that point. As administered in this study, trovafloxacin was as efficacious as doxycycline but azithromycin proved less efficacious, possibly due to the short duration of administration.

The lens influences aqueous humor levels of transforming growth factor-β2

Abstract · Background: Transforming growth factor-beta 2 (TGF-β2) is a pluripotent cytokine which has been suggested to play a number of roles in ocular physiologic and pathologic states. Intraocular fluid (IOF) levels of TGF-β2 are quite high. Although the sources of ocular TGF-β are not completely defined, the retinal pigment epithelium, the epithelium of the ciliary body and trabecular meshwork cells all secrete it. In this study we utilized canine lens and rabbit ciliary pigmented epithelial cell cultures to quantitate the in vitro secretion of TGF-β2. In addition, the effects of aphakia or the presence of cataractous lenses on IOF TGF-β2 levels were determined. · Methods: Lens and ciliary body epithelial cell culture supernatants and aqueous humors were assayed for total TGF-β2 levels by ELISA and bioassay. · Results: TGF-β2 accumulated in the media bathing lens epithelial cell cultures (0.7 ± 0.03 ng/ml at day 2) and ciliary pigmented epithelial cell cultures (0.8 ± 0.06 ng/ml at day 2) in a time-dependent manner. Surprisingly, aqueous humor from aphakic rabbit eyes contained significantly higher levels of TGF-β2 than their contralateral phakic controls. Furthermore, aqueous humor from canine eyes with cataracts also contained significantly higher levels of TGF-β2 than normal eyes. · Conclusions: These results suggest that the lens secretes TGF-β2 and that the presence and status of the lens may influence IOF TGF-β2 levels.

Elevated Interleukin-10-to-Interleukin-12 Ratio in Feline Immunodeficiency Virus-Infected Cats Predicts Loss of Type 1 Immunity to Toxoplasma gondii

Similar to human immunodeficiency virus, feline immunodeficiency virus (FIV) induces immunodeficiency and enhanced susceptibility to secondary pathogens. To explore cytokine alterations in lentivirus immunodeficiency, constitutive mRNA expression was measured in lymph nodes of healthy and FIV-infected cats before and after challenge with Toxoplasma gondii. Cytokine mRNA expression was similar in control and FIV-infected cats during the first 10 weeks after infection. At 16 weeks, interferon (IFN)-gamma, tumor necrosis factor-alpha, and interleukin (IL)-10 mRNA were increased in FIV-infected cats. Challenge with T. gondii induced an increase in IL-2, IFN-gamma, and IL-12 in the lymph nodes of control cats, whereas IFN-gamma and IL-10 but not IL-2 or IL-12 increased in the lymph nodes of FIV-T. gondii coinfected cats. These results indicate that FIV immunodeficiency may derive from a failure to generate an IL-12-dependent type 1 response and that an elevated level of IL-10 mRNA expression is a predictor of lentivirus immunodeficiency.

Effect of surgical technique on in vitro posterior capsule opacification

Purpose: To compare the effect of different cataract extraction surgical techniques on residual lens epithelial cell (LEC) density and cell regrowth rates using an in vitro model of posterior capsule opacification (PCO). Setting: Comparative Ophthalmology Research Laboratories, North Carolina State University, Raleigh, North Carolina, USA. Methods: Lens capsule explants were prepared from freshly enucleated canine globes after extracapsular cataract extraction (ECCE), phacoemulsification, or phacoemulsification followed by capsule vacuuming. Initial cell density on the capsule and cell proliferation were determined by phase contrast microscopy. The effects of the surgical technique on time to confluent growth of the cells across the posterior lens capsule were determined. Results: Residual cell density on the remaining anterior capsule immediately after lens removal was 31.6% ± 19.3%, 16.1% ± 8.9%, and 7.7% ± 5.7% in the ECCE, phacoemulsification, and phacoemulsification/capsule‐vacuuming groups, respectively. Time to confluence (range 5.0 to 6.3 days) was not significantly different among the 3 groups when the lens capsules were cultured in serum‐supplemented media. The confluence rate was significantly longer (by approximately 5 to 7 days) in the phacoemulsification/capsule‐vacuuming group than in the other 2 groups when the capsules were cultured in serum‐free media. Conclusions: Phacoemulsification with and without anterior and equatorial capsular vacuuming led to less initial LEC density in the capsular bag than ECCE. However, because cell proliferation rates among the 3 groups were only marginally affected, near 100% removal of LEC at the time of cataract extraction may be necessary to prevent PCO.

Efficacy of chloramphenicol, enrofloxacin, and tetracycline for treatment of experimental Rocky Mountain spotted fever in dogs.

Dogs were experimentally inoculated with Rickettsia rickettsii to characterize the comparative efficacies of chloramphenicol, enrofloxacin, and tetracycline for the treatment of Rocky Mountain spotted fever (RMSF). All three antibiotics were equally effective in abrogating the clinical, hematologic, and vascular indicators of rickettsial infection. Antibiotic treatment for 24 h was sufficient to decrease the rickettsemia to levels below detection by Vero cell culture. Early treatment with all three antibiotics resulted in a similar decrease in antibody titer, but acute and convalescent serum samples taken at appropriate times would have still facilitated an accurate diagnosis of RMSF in all but one dog, which did not seroconvert. We conclude that chloramphenicol, enrofloxacin, and tetracycline are equally efficacious for treating experimental canine RMSF.

Ex vivo canine lens capsular sac explants.

Abstract Background: Lens capsular sac explants from human cadaver eyes were used to investigate posterior capsular opacification (PCO). The purpose of this study was to characterize a similar model using canine tissue and to determine whether transferrin (Tf), transforming growth factor β-2 (TGF-β2), and insulin-like growth factor-1 (IGF-1) are secreted by lens epithelial cells (LEC) of these ex vivo sacs. Methods: The lens from canine eyes was removed by extracapsular cataract extraction, the lens sac dissected free, pinned to a petri dish, and cultured in either serum-supplemented or serum-free medium. Morphologic characteristics and growth rate to confluence on the posterior capsule were studied by phase-contrast microscopy. Vimentin, alpha smooth muscle actin, and panTGF-β expression by LEC were determined by immunohistochemistry. Tf, TGF-β2, and IGF-1 levels were measured by ELISA in the supernatant of sacs cultured in serum-free medium. Results: The mean time to confluence of LEC onto the posterior capsule was 5.4±1.1 days (n=22) and 14.7±3.7 days (n=14) for sacs in serum-supplemented and serum-free medium, respectively. Following development of confluence, explants displayed opacification and light scatter from cellular proliferation and capsular contraction. Confluent LEC expressed vimentin, alpha smooth muscle actin, and TGF-β2, and both Tf and TGF-β2 were secreted into the culture supernatant. Conclusion: Canine lens sac explants have characteristics virtually identical to those of human origin, and appear to be a useful alternative tissue source for this model when human cadaver eyes are unavailable. Tf and TGFβ-2, but not IGF-1, are secreted by LEC in explanted lens sacs and may influence the proliferation and metaplasia of LEC during the development of PCO.

The intracapsular extraction of displaced lenses in dogs: a retrospective study of 57 cases (1984-1990).

Records of 48 dogs (57 eyes) that underwent intracapsular lens extraction (ICLE) of displaced lenses were reviewed. Preoperatively, 73% (19/26 eyes) of eyes with anterior luxations had secondary glaucoma compared to 43% (10/23 eyes) with subluxations and 38% (3/8 eyes) with posterior luxations. Forty-one of 57 eyes (72%) had vision and intraocular pressure (IOP) less than 30 mm Hg four to six weeks after surgery. This percentage declined to 61% (22/36 eyes) in three months and 53% (8/15 eyes) in 12 months. Eyes with glaucoma before ICLE had a lower success rate (66%) than eyes without (82%). Since secondary glaucoma was the most common cause of failure, this study suggests that removal of a subluxated lens or a posteriorly luxated lens should be recommended before the lens moves into the anterior chamber.

Regulated over-expression of DNA polymerase β mediates early onset cataract in mice

Base excision repair (BER) is a tightly coordinated mechanism for repair of DNA base damage (via alkylation and oxidation) and base loss. From E. coli to yeast to human cells, subtle alterations in expression of BER proteins lead to mutagenic or genome instability phenotypes. DNA polymerase beta (beta-pol), the major BER polymerase, has been found to be over-expressed in human tumor tissues and more recently it has been shown that over-expression of beta-pol results in a mutator and genome instability phenotype. These previous reports imply that beta-pol over-expression is deleterious and suggests that such an imbalance may cause an overall functional deficiency in the BER pathway. In the present study, we have developed a bicistronic tetracycline-responsive transgenic system to over-express beta-pol in mice. We find that over-expression of beta-pol in the lens epithelium results in the early onset of severe cortical cataract, with cataractogenesis beginning within 4 days after birth. In utero and post-natal suppression of transgenic Flag-beta-pol expression by doxycycline administration completely prevents cataract formation through adulthood, yet cataract is subsequently observed following removal of doxycycline and re-expression of the transgene. Cataract development accompanies increased expression of cyclooxygenase-2 in the lenticular fibers of the lens, implicating oxidative stress in the development of this cataractous phenotype. Although the mechanism for the transgene mediated cataractogenesis is not clear at this time, it is nevertheless intriguing that increased expression of beta-pol leads to such a phenotype. These results suggest that either a beta-pol expression imbalance negatively affects overall fidelity and/or BER capacity or that beta-pol has a role in lens epithelial cell differentiation.