Journal of Veterinary Internal Medicine最新文献

Background: Effective treatments for dogs with advanced stage mast cell tumors (MCT) remain a pressing need. A micellar formulation of paclitaxel (paclitaxel [micellar]) has shown promise in early-phase studies.

Hypothesis/objectives: The objective was to demonstrate greater activity for paclitaxel (micellar) compared with lomustine. The null hypothesis was μ(p) = μ(L) (ie, proportion of responders for the paclitaxel [micellar] and lomustine groups, respectively).

Animals: Two hundred and fifty-two dogs with advanced stage nonresectable grade 2 or 3 MCT.

Methods: Prospective multicenter randomized double-blind positive-controlled clinical trial. The primary endpoint was confirmed overall response rate (CORR) at 14 weeks. A secondary endpoint, biologic observed response rate (BORR), also was calculated. Safety was assessed by the characterization and grading of adverse events (AE).

Results: Overall CORR (7% versus 1%; P = .048) and BORR (23% versus 10%; P = .012) were greater for paclitaxel (micellar) compared with lomustine. Paclitaxel (micellar)-treated dogs were 6.5 times more likely to have a confirmed response and 3.1 times more likely to experience a biologic observed response. The majority of AE with paclitaxel (micellar) were transient and clinically manageable. Twenty-seven dogs (33%) receiving lomustine were discontinued because of hepatopathy compared with 3 dogs (2%) receiving paclitaxel (micellar) (P < .0001; odds ratio 26.7).

Conclusions and clinical importance: Paclitaxel (micellar)'s activity and safety profile are superior to lomustine. The addition of an active and novel taxane to the veterinary armamentarium could fill a substantial need and, as its mechanism of action and AE profile do not overlap with currently available TKI, its availability could lead to effective combination protocols.

Background: Many Crotalaria plant species contain hepatotoxic pyrrolizidine alkaloids (such as monocrotaline) that can cause acute and chronic poisoning in cattle and other animals.

Hypothesis: Peanut oil, atropine sulfate, and antidiarrheal agents are used to treat acute monocrotaline poisoning. The effect of sesame on acute monocrotaline poisoning has never been investigated.

Animals: Fifty male Sprague-Dawley rats were used for toxicity studies.

Methods: Experiment 1: Group I, control. Groups II-IV were given monocrotaline (205.2 mg/kg) and euthanized 6, 12, and 24 hours later. Experiment 2: Group I, control. Group II monocrotaline alone (205.2 mg/kg). Groups III-VI were given monocrotaline (205.2 mg/kg) and 1 hour later, Groups III and IV were given sesame oil (1 and 2 mL/kg) and Groups V and VI were given peanut oil (1 and 2 mL/kg).

Results: Monocrotaline significantly decreased (P < .05) serum amylase activity, but, over time, increased (P < .05) pancreatic and lung injury. AST and ALT activity and liver injury peaked at 24 hours. Sesame oil and peanut oil (P < .05) inhibited the changes in all tested parameters in acute monocrotaline poisoning. Although peanut oil inhibited acute monocrotaline poisoning, it induced steatosis, but sesame oil did not.

Conclusion and clinical importance: We hypothesize that early pancreatic and lung injury and late liver injury contribute to acute monocrotaline poisoning and that sesame oil is more efficacious than peanut oil against acute monocrotaline poisoning in rats. However, additional studies are needed to confirm that these oils have the same effects in cattle and other animals.

Background: Systemic hypertension and proteinuria are frequent complications in dogs with Cushing's syndrome and do not always resolve after treatment of hypercortisolism. Therefore, dogs with Cushing's syndrome may be at risk for renal dysfunction before and after treatment.

Hypothesis/objectives: To assess renal function in dogs with ACTH-dependent hyperadrenocorticism (ADHAC) before and after treatment.

Animals: A total of 19 dogs with ADHAC and 12 control dogs.

Methods: Renal function was assessed before and at 1, 3, 6, and 12 months after treatment. Twelve dogs were treated with trilostane and 7 dogs by transsphenoidal hypophysectomy. Routine renal markers were measured and urinary albumin (uALB), immunoglobulin G (uIgG), and retinol-binding protein (uRBP) were assessed by ELISA. Urinary N-acetyl-β-D-glucosaminidase (uNAG) was determined colorimetrically. All urinary markers were indexed to urinary creatinine concentration (c). Plasma clearance of creatinine (Cl(creat)), exo-iohexol (Cl(exo)), and endo-iohexol (Cl(endo)) was used to measure glomerular filtration rate (GFR). Data were analyzed using a general linear model.

Results: Serum creatinine and urea concentrations increased post-treatment, but remained within reference ranges. Plasma Cl(creat) and Cl(endo) were significantly lower post-treatment, whereas Cl(exo) was not different. Urinary protein-to-creatinine ratio (UPC), uALB/c, uIgG/c, and uRBP/c were decreased post-treatment, but at 12 months 5/13 dogs remained proteinuric. Urinary NAG/c did not change significantly.

Conclusions and clinical importance: A decrease in GFR and persistent proteinuria post-treatment may warrant the clinician's attention. Future research including renal histopathology of dogs with persistent proteinuria or low GFR is needed to further assess renal outcome.

Background: Heparin therapy is difficult to monitor due to variation in animal response. While laboratory measurements of activated partial thromboplasin time (aPTT) and Anti-Xa activity (AXA) accurately describe heparin effect, their availability is limited.

Hypothesis: Sonoclot analysis would be as sensitive as AXA and aPTT to monitor effects of unfractionated heparin (UFH) in healthy adult dogs.

Animals: Six adult mixed-breed dogs.

Methods: A prospective study design was employed. On day 1, baseline samples were collected (CBC, PT, aPTT, and Sonoclot), and UFH (300 U/kg SC) was administered to 6 dogs following an IV loading dose of 50 U/kg. Sonoclot and aPTT were performed hourly for 12 hours. AXA was assayed at hours 3, 6, 9, and 12. UFH (300 U/kg q8 h SC) was administered at 12 hours, and subsequently (q8 h) for 2 additional days. On day 4, a final dose of UFH was administered, and a sampling protocol identical to day 1 was performed.

Results: Sonoclot activated clotting time (ACT) and clot rate (CR) correlated with AXA (R = 0.69, R = 0.65, respectively, P < .001), although to a lesser degree than aPTT (R = 0.75, P < .001). Linear regression using ACT and CR as covariates indicated a stronger correlation with AXA (R = 0.73, P < .001). ACT values strongly correlated with aPTT (R = 0.87, P < .001).

Conclusions and clinical importance: Administration of UFH to healthy dogs results in progressive changes in Sonoclot values. AXA was correlated with a combination of ACT and CR and with aPTT. Sonoclot may play a role in monitoring UFH therapy; however, prospective studies evaluating its utility in clinical cases are warranted.

Background: Blood samples banked for up to 1 month are typically used to perform pretransfusion testing in humans and small animals, but this has not been validated using blood from horses.

Hypothesis: Compatibility of equine blood samples is repeatable using fresh samples, and reproducible using donor blood samples stored for up to 4 weeks.

Animals: Six healthy adult horses.

Methods: Randomized, blinded experimental study. Immunologic compatibility of the blood of all horses was assessed using a major and minor saline agglutination and hemolysin crossmatch using blood samples refrigerated for 0-4 weeks and fresh blood from the same horses. Crossmatch results were scored and then compared to identify changes of compatibility in each of the 4 tests. In addition, repeatability of the crossmatch technique itself was assessed by performing 6 iterations of this procedure in immediate succession with fresh blood from 3 horses.

Results: No significant difference in crossmatch results was found using fresh blood (P = .39-1.00). Reproducibility was poor using blood stored for 1-4 weeks, especially in tests using stored erythrocytes (major antigen crossmatches), with significant differences from baseline at all weeks (P < .05); 13 of these differences were positive, indicating poorer compatibility.

Conclusions and clinical importance: Equine blood crossmatching is repeatable using fresh blood, although decreased apparent compatibility after storage makes exclusion of compatible donors more likely than mistaken administration of incompatible blood. These data suggest that fresh samples should be collected from potential donors before crossmatching equine blood.

Background: The clinical manifestations of acute kidney injury (AKI) range from mild to fatal in cats; however, prognosis factors have been rarely studied.

Hypothesis/objectives: To find the clinical factors significantly correlated with the outcome among cats with AKI and to develop a simple prognostic index.

Animals: Seventy cats with AKI were recruited.

Methods: Demographic and clinicopathological data obtained from 70 cats with AKI were retrospectively collected. Student's t-test or Mann-Whitney U-test and Pearson chi-square test or Fisher's exact were applied to determine the factors associated with survival in cats with AKI. Using logistic regression, the statistically significant factors associated with prognosis were identified and a new prediction model was generated.

Results: The overall case fatality rate was 64% (45/70). The results showed that nonsurviving cats had significantly lower levels of PCV, WBC, RBC, LDH and albumin, a lower albumin/globulin ratio, lower blood glucose, and a reduced body temperature, as well as being older. Serum urea and creatinine concentrations were not statistically significant as prognostic factors, but a decrease in these 2 variables in 3 days was significantly related to a reduction in death. A summary prognostic index including body temperature and LDH and albumin concentrations had area under the receiver-operating characteristic curve (AUROC) for predicting death of 0.86 (P < .05) and a cut-off value of 0.82, a sensitivity of 77% and a specificity of 90%.

Conclusions: The prognosis in cats with AKI is quite different from that found for human and dogs.

Background: In human patients with interstitial cystitis, intravesical instillation of alkalinized lidocaine sometimes is associated with sustained amelioration of symptoms beyond the acute treatment phase. Interstitial cystitis shares many features in common with feline idiopathic cystitis.

Objective: To evaluate whether intravesical instillation of alkalinized lidocaine decreases recurrence of urethral obstruction and severity of clinical signs in cats with obstructive idiopathic LUTD.

Animals: Twenty-six cats with obstructive idiopathic LUTD. Twelve cats in case group (treatment with alkalinized lidocaine) and 14 control cats (treatment with placebo or standard treatment).

Methods: Cats were randomly assigned to treatment (2 or 4 mg/kg lidocaine and sodium bicarbonate) or placebo groups (0.2 mL/kg saline solution and sodium bicarbonate). The intravesical instillation was done once a day for 3 days. Some cats underwent standard treatment only (indwelling urinary catheter for 3 days without intravesical instillations). A 2-week, 1-month, and 2-month follow-up after treatment was made using a questionnaire. The recurrence rate and amelioration scores of clinical signs were assessed and compared.

Results: Recurrence of urethral obstruction was 58% (7/12) in the case group and 57% (8/14) in the control group. Amelioration scores were similar between the 2 groups.

Conclusion and clinical importance: Intravesical administration of lidocaine for up to 3 consecutive days had no apparent beneficial effect on decreasing recurrence rate and severity of clinical signs in cats with obstructive idiopathic LUTD.

Background: Uncomplicated urinary tract infections (UTI) in dogs usually are treated with antimicrobial drugs for 10-14 days. Shorter duration antimicrobial regimens have been evaluated in human patients.

Hypothesis: A high dose short duration (HDSD) enrofloxacin protocol administered to dogs with uncomplicated UTI will not be inferior to a 14-day treatment regimen with amoxicillin-clavulanic acid.

Animals: Client-owned adult, otherwise healthy dogs with aerobic bacterial urine culture yielding ≥ 10(3) CFU/mL of bacteria after cystocentesis.

Methods: Prospective, multicenter, controlled, randomized blinded clinical trial. Enrolled dogs were randomized to group 1 (enrofloxacin 18-20 mg/kg PO q24h for 3 days) or group 2 (amoxicillin-clavulanic acid 13.75-25 mg/kg PO q12h for 14 days). Urine cultures were obtained at days 0, 10, and 21. Microbiologic and clinical cure rates were evaluated 7 days after antimicrobial treatment was discontinued. Lower urinary tract signs and adverse events also were recorded.

Results: There were 35 dogs in group 1 and 33 in group 2. The microbiologic cure rate was 77.1 and 81.2% for groups 1 and 2, respectively. The clinical cure rate was 88.6 and 87.9% for groups 1 and 2, respectively. Cure rates between groups did not differ according to the selected margin of noninferiority.

Conclusions and clinical importance: HDSD enrofloxacin treatment was not inferior to a conventional amoxicillin-clavulanic acid protocol for the treatment of uncomplicated bacterial UTI in dogs. Further research is warranted to determine if this protocol will positively impact owner compliance and decrease the emergence of antimicrobial resistance.

Background: The pathophysiology of thrombus formation in canine IMHA and other diseases remains unclear. Antiphospholipid antibodies (aPL) are an important cause of thrombosis in humans and might cause thrombosis in dogs.

Hypothesis: Dogs with IMHA, spontaneous thrombosis, and hyperadrenocorticism will have increased levels of aPL and lupus anticoagulants (LA), compared with healthy and sick dogs.

Animals: Thre aPL were measured in healthy controls (n = 40-45); sick dogs without thrombosis (n = 86); IMHA (n = 37); spontaneous thrombosis (ST, n = 11); and hyperadrenocorticism (n = 17). Four groups of dogs were also tested for the presence of LA: healthy controls (n = 40); sick dogs without thrombosis (n = 13); IMHA (n = 13); and ST (n = 5).

Methods: Prospective cohort study. Dogs were tested for aPL by an ELISA and for LA by the dilute Russell's Viper venom time (dRVVT). Median values were compared by Kruskal-Wallis (aPL) or ANOVA (LA), and an odds ratio for development of thrombosis in dogs positive for aPL was calculated.

Results: aPL are uncommon in healthy dogs. A total of 13/86 sick dogs without thrombosis, 7/37 dogs with IMHA, 1/11 dogs with ST, and 3/17 dogs with HAC were positive for protein binding-dependent aPL. There was no significant difference in the number of dogs positive for aPL for any of the study groups, and there was no increased risk for thrombosis in dogs positive for aPL. No dogs had LA.

Conclusions: Our preliminary research does not support a strong role for aPL for the development of thrombosis in dogs with IMHA and other thrombotic diseases, although future studies are warranted.

Background: Diagnosis of pituitary-dependent hyperadrenocorticism (PDH) in cats is challenging because there is no specific diagnostic test.

Hypothesis/objective: The determination of plasma ACTH precursor (POMC and pro-ACTH) concentration might facilitate the diagnosis of PDH in cats. The aim of the study was to evaluate prospectively the plasma concentrations of ACTH precursors in a small cohort of cats with PDH and to estimate the value of this approach for diagnosis.

Animals: Four groups of cats were included: group 1 (cats with PDH), group 2 (cats with diabetes mellitus but not hyperadrenocorticism (HAC)), group 3 (cats with diabetes mellitus and confirmed acromegaly but not HAC), and group 4 (healthy cats).

Methods: PDH diagnosis was based on clinical data, low-dose dexamethasone suppression test (LDDST), and adrenal and pituitary gland computed tomography (CT) scan. For groups 2, 3, and 4, hyperadrenocorticism was excluded by LDDST or urine cortisol:creatinine ratio (UCCR). An immunoluminometric assay was used to determine plasma concentrations of ACTH precursors in the 4 groups of cats.

Results: Group 1 contained 9 cats (enlarged pituitary gland in 7/9). Plasma ACTH precursor concentrations ranged from <53 to >1010 pmol/L with 8/9 concentrations ≥ 229 pmol/L. Groups 2, 3, and 4 included 13, 7, and 13 cats, respectively. Plasma ACTH precursor concentrations ranged from <53 to 96 pmol/L in group 2, <53 to 72 pmol/L in group 3, and <53 to 99 pmol/L in group 4.

Conclusion and clinical importance: High plasma concentration of ACTH precursors in cats (>100 pmol/L) is highly suggestive of PDH.