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SUMMARY

Thirty-five heifers were allotted to 3 groups. Group 1 (control) consisted of 10 heifers that were not vaccinated and were challenge exposed by breeding to infected bulls. Group 2 (natural challenge exposure) consisted of 10 heifers that were vaccinated and challenge exposed by breeding to infected bulls. Group 3 (experimental challenge exposure) consisted of 15 heifers that were vaccinated and challenge exposed by breeding to infected bulls and by intravaginal inoculation with 107 Tritrichomonas foetus. Total immunoglobulin concentrations and specific trichomonal antibodies were determined in serum and vaginal secretions of heifers, using radial immunodiffusion and elisa procedures.

Control heifers remained infected for a mean of 10.6 weeks (range, 0 to 18 weeks), and heifers of the natural and experimental challenge-exposure groups remained infected for 3.2 and 5.0 weeks, respectively (range, 0 to 12 weeks). Total serum and cervicova- ginal mucus concentrations of IgM, IgA, IgG1, and IgG2 did not change significantly after vaccination or challenge exposure. However, elisa titers of total trichomonal antibodies increased up to 1:10,000 (range, 1:400 to 1:10,000) in serum after vaccination, and increased approximately tenfold above background in cervicovaginal mucus. In serum, the predominant trichomonal antibody isotype was IgG1, although trichomonal IgA and IgM antibodies also increased. The predominant trichomonal antibody detected in cervicovaginal mucus was IgA. Antibody titers in serum and cervicovaginal mucus of vaccinated heifers were not increased by infection. However, in control heifers, the total local trichomonal antibody response increased three- to fivefold after infection. In these heifers, specific antibodies in serum were predominantly IgGI and local (cervicovaginal) antibodies were predominantly IgA.

Free access
in American Journal of Veterinary Research

Summary

To test the efficacy of a polyvalent Tritrichomonas foetus vaccine, 130 nulliparous heifers were randomly assigned to either receive the test T foetus vaccine or to serve as nonvaccinated controls. The polyvalent test vaccine consisted of a Campylobacter fetus/Leptospira canicola-grippotyphosa-hardjo-icterohaemorrhagiae-pamona bacterine containing 5 × 107 killed T foetus/dose. The polyvalent control vaccine consisted of the aforementioned formulation without T foetus. Heifers were administered 2 doses of control or experimental vaccine at 3-week intervals. Heifers were bred to T foetus-infected bulls and their conception and pregnancy rates were determined throughout gestation. In addition, serum samples were analyzed to determine induced concentrations of antitrichomonal antibodies and vaginal secretions were sampled to determine T foetus infection rates in control and vaccinated animals. One week after each of the 15-day breeding periods, 60% (6 of 10) of tested vaccinates and 80% (8 of 10) of tested control animals were T foetus culture-positive. The mean duration of infection of vaccinates was 3.8 weeks (± 7.5 days), compared with 5.4 weeks (± 7.5 days) of infection for control heifers. All vaccinates developed increased immunofluorescence and serum neutralizing antibody titers following the first immunization, and had additional increases of at least fourfold in response to the second injection. In contrast, no consistent increase in immunofluorescence or serum neutralizing antibodies was observed in control animals.

Conception rates were 89.2% for vaccinates and 85.9% for control animals 30 days after breeding and 80 to 90% of these remained pregnant 60 days after breeding. However, within the next 4 months, the pregnancy rate of control heifers decreased to 30% for those that had conceived. During the same 4-month period, more than 60% of vaccinated heifers remained pregnant. Significantly, 62.5% of heifers vaccinated against T foetus produced calves, whereas only 31.5% of control heifers produced calves. These findings indicate that the polyvalent test vaccine induced an immune response that was effective in lowering the rate of T foetus infection, decreasing the duration of infection, and reducing losses in calf production attributable to early fetal death and abortion caused by T foetus infection.

Free access
in American Journal of Veterinary Research

Abstract

Objective—To compare long-term survival and quality of life data in dogs with clinical signs associated with a congenital portosystemic shunt (CPSS) that underwent medical or surgical treatment.

Design—Prospective cohort study.

Animals—124 client-owned dogs with CPSS.

Procedures—Dogs received medical or surgical treatment without regard to signalment, clinical signs, or clinicopathologic results. Survival data were analyzed with a Cox regression model. Quality of life information, obtained from owner questionnaires, included frequency of CPSS-associated clinical signs (from which a clinical score was derived), whether owners considered their dog normal, and (for surgically treated dogs) any ongoing medical treatment for CPSS. A Mann-Whitney U test was used to compare mean clinical score data between surgically and medically managed dogs during predetermined follow-up intervals.

Results—97 dogs underwent surgical treatment; 27 were managed medically. Median follow-up time for all dogs was 1,936 days. Forty-five dogs (24 medically managed and 21 surgically managed) died or were euthanized during the follow-up period. Survival rate was significantly improved in dogs that underwent surgical treatment (hazard ratio, 8.11; 95% CI, 4.20 to 15.66) than in those treated medically for CPSS. Neither age at diagnosis nor shunt type affected survival rate. Frequency of clinical signs was lower in surgically versus medically managed dogs for all follow-up intervals, with a significant difference between groups at 4 to 7 years after study entry.

Conclusions and Clinical Relevance—Surgical treatment of CPSS in dogs resulted in significantly improved survival rate and lower frequency of ongoing clinical signs, compared with medical management. Age at diagnosis did not affect survival rate and should not influence treatment choice.

Full access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To compare survival of dogs with a congenital portosystemic shunt (CPSS) that received medical or surgical treatment.

Design—Prospective cohort study.

Animals—126 client-owned dogs with a single CPSS.

Procedures—Dogs were examined at 1 of 3 referral clinics, and a single CPSS was diagnosed in each. Dogs received medical or surgical treatment without regard to signalment, clinical signs, or results of hematologic or biochemical analysis. Survival data were analyzed via a Cox regression model.

Results—During a median follow-up period of 579 days, 18 of 126 dogs died as a result of CPSS. Dogs treated via surgical intervention survived significantly longer than did those treated medically. Hazard ratio for medical versus surgical treatment of CPSS (for the treatment-only model) was 2.9 (95% confidence interval, 1.1 to 7.2). Age at CPSS diagnosis did not affect survival.

Conclusions and Clinical Relevance—Both medical and surgical treatment can be used to achieve long-term survival of dogs with CPSS, although results of statistical analysis supported the widely held belief that surgery is preferable to medical treatment. However, the study population consisted of dogs at referral clinics, which suggested that efficacy of medical treatment may have been underestimated. Although surgical intervention was associated with a better chance of long-term survival, medical management provided an acceptable first-line option. Age at examination did not affect survival, which implied that early surgical intervention was not essential. Dogs with CPSS that do not achieve acceptable resolution with medical treatment can subsequently be treated surgically.

Full access
in Journal of the American Veterinary Medical Association

Abstract

OBJECTIVE

To establish the pharmacokinetics of the cyclin-dependent kinase-9 inhibitor flavopiridol in equine middle carpal joints, using an extended-release poly lactic-co-glycolic acid (PLGA) microparticle formulation.

ANIMALS

4 healthy horses without evidence of forelimb lameness.

METHODS

A 6-week longitudinal pharmacokinetic study was conducted in 2 phases (6 weeks each) in 4 healthy horses. The PLGA microparticles containing 122 μg flavopiridol in 3 mL saline were administered by intra-articular injection into 1 middle carpal joint, with empty PLGA microparticles injected into the contralateral joint as a control. Synovial fluid and plasma were collected at time points out to 6 weeks, and drug concentrations in synovial fluid and plasma were determined using validated protocols. Synovial fluid total protein and total nucleated cell count and differential, CBC, serum biochemistry, and lameness exams were performed at each of the time points.

RESULTS

Synovial fluid flavopiridol averaged 19 nM at week 1, gradually reduced to 1.4 nM by 4 weeks, and was generally below the detection limit at 5 and 6 weeks. There was no detectable flavopiridol in the plasma samples, and no adverse effects were observed at any time point.

CLINICAL RELEVANCE

Intra-articular injection of PLGA microparticle-encapsulated flavopiridol was well tolerated in horses, with detectable levels of flavopiridol in the synovial fluid out to 4 weeks with negligible systemic exposure. Flavopiridol is a cyclin-dependent kinase-9 inhibitor with potent anti-inflammatory and analgesic activity. The extended-release microparticle formulation promotes intra-articular retention of the drug and it may be an alternative to other intra-articular medications for treatment of equine joint disease.

Open access
in American Journal of Veterinary Research