Dorothy Cimino Brown

Deletion of vanilloid receptor 1-expressing primary afferent neurons for pain control

Control of cancer, neuropathic, and postoperative pain is frequently inadequate or compromised by debilitating side effects. Inhibition or removal of certain nociceptive neurons, while retaining all other sensory modalities and motor function, would represent a new therapeutic approach to control severe pain. The enriched expression of transient receptor potential cation channel, subfamily V, member 1 (TRPV1; also known as the vanilloid receptor, VR1) in nociceptive neurons of the dorsal root and trigeminal ganglia allowed us to test this concept. Administration of the potent TRPV1 agonist resiniferatoxin (RTX) to neuronal perikarya induces calcium cytotoxicity by opening the TRPV1 ion channel and selectively ablates nociceptive neurons. This treatment blocks experimental inflammatory hyperalgesia and neurogenic inflammation in rats and naturally occurring cancer and debilitating arthritic pain in dogs. Sensations of touch, proprioception, and high-threshold mechanosensitive nociception, as well as locomotor function, remained intact in both species. In separate experiments directed at postoperative pain control, subcutaneous administration of RTX transiently disrupted nociceptive nerve endings, yielding reversible analgesia. In human dorsal root ganglion cultures, RTX induced a prolonged increase in intracellular calcium in vanilloid-sensitive neurons, while leaving other, adjacent neurons unaffected. The results suggest that nociceptive neuronal or nerve terminal deletion will be effective and broadly applicable as strategies for pain management.

The effect of laparoscopic versus open ovariectomy on postsurgical activity in small dogs.

OBJECTIVE To describe a technique for laparoscopic ovariectomy (LapOVE) in small dogs, and compare the surgical time, complications, and postoperative activity of dogs undergoing LapOVE to those undergoing conventional traditional open ovariectomy (OOVE). STUDY DESIGN A randomized, controlled clinical trial. ANIMALS Intact small breed (<10 kg) female dogs (n=20). METHODS Ventral median celiotomy was performed for OOVE. A 2-midline portal technique using a 3.5 mm laparoscope port and a 6 mm instrument portal was used for LapOVE. An accelerometer was attached to the collar of each dog to record 24-hour preoperative and 48-hour postoperative activity. Total activity counts recorded before surgery were compared with total counts recorded after surgery. The percent change in counts after surgery was compared between OOVE- and LapOVE-treated dogs. RESULTS No major complications occurred and surgical time for LapOVE was significantly longer than for OOVE cases (P=.005). Dogs in the LapOVE group had a 25% decrease in total activity counts after surgery (95% confidence interval [CI]: 11-38%), whereas dogs in the OOVE group had a 62% decrease in total activity counts after surgery (95% CI: 48-76%). CONCLUSIONS Both procedures were performed with reasonable surgical times and without major complication. Postoperative activity, as measured by accelerometry, was significantly different between the 2 groups. CLINICAL RELEVANCE Laparoscopy is a safe method for ovariectomy in small dogs and results in increased postoperative activity counts when compared with an open technique.

Physiologic and antinociceptive effects of intrathecal resiniferatoxin in a canine bone cancer model

Background:Resiniferatoxin is a potent capsaicin analog. Intrathecal administration leads to selective, prolonged opening of the transient receptor potential V1 ion channel, which is localized mainly to C-fiber primary afferent nociceptive sensory neurons. Following work in laboratory animals, the authors explored the use of intrathecal resiniferatoxin to control spontaneous bone cancer pain in companion (pet) dogs. Methods:Normal canine population: Behavioral testing was performed to establish baseline paw withdrawal latency; subsequently, general anesthesia was induced and resiniferatoxin was administered intrathecally while hemodynamic parameters were recorded. Behavior testing was repeated for 12 days after administration of resiniferatoxin. Clinical canine population: Twenty companion dogs with bone cancer pain were recruited. The animal’s baseline level of discomfort and analgesic use were recorded. Resiniferatoxin was administered intrathecally and hemodynamic parameters were monitored while the dogs were under general anesthesia. Dogs were reevaluated up to 14 weeks after resiniferatoxin administration. Results:Normal canine population: In the first minutes after resiniferatoxin injection, there were significant (P < 0.05) increases in mean arterial blood pressure and heart rate from baseline. Two days after injection, limb withdrawal latencies increased to the point of cutoff in the dogs that received at least 1.2 &mgr;g/kg resiniferatoxin. Clinical canine population: From baseline, there were significant (P < 0.05) increases in mean arterial blood pressure and heart rate after resiniferatoxin injection. Comfort scores were significantly improved at 2, 6, 10, and 14 weeks after resiniferatoxin administration (P < 0.0001). There was decreased or discontinued use of supplemental analgesics in 67% of the dogs 2 weeks after resiniferatoxin administration. Conclusions:Intrathecal resiniferatoxin elicits transient hemodynamic effects. In controls, a profound and sustained blockade of thermal stimuli is produced in a dose-dependent fashion. Similar administration in dogs with bone cancer produces a prolonged antinociceptive response.

Proposed Definitions and Criteria for Reporting Time Frame, Outcome, and Complications For Clinical Orthopedic Studies in Veterinary Medicine

Outcome, and Complications For Clinical Orthopedic Studies in Veterinary Medicine James L. Cook, DVM, PhD, Diplomate ACVS, Richard Evans, PhD, Michael G. Conzemius, DVM, PhD, Diplomate ACVS, B. Duncan X. Lascelles, BVSc, PhD, Diplomate ECVS, Diplomate ACVS, C. Wayne McIlwraith, BVSc, PhD, Diplomate ACVS, Antonio Pozzi, DMV, MS, Diplomate ACVS, Peter Clegg, MA, VetMB, PhD, Diplomate ECVS, MRCVS, John Innes, BVSc, PhD, DSAS (Orth), MRCVS, Kurt Schulz, DVM, Diplomate ACVS, John Houlton, MA, VetMB, DVR, DSAO, MRCVS, Diplomate ECVS, Lisa Fortier, DVM, PhD, Diplomate ACVS, Alan R. Cross, DVM, Diplomate ACVS, Kei Hayashi, DVM, PhD, Diplomate ACVS, Amy Kapatkin, DVM, MS, Diplomate ACVS, Dorothy Cimino Brown, DVM, MSCE, Diplomate ACVS, and Allison Stewart, DVM, MS, Diplomate ACVS Comparative Orthopaedic Laboratory, University of Missouri, Columbia, MO, College of Veterinary Medicine, University of Illinois, Urbana, IL, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, Comparative Pain Research Laboratory, North Carolina State University,

Prediction of first onset of congestive heart failure in dogs with degenerative mitral valve disease: the PREDICT cohort study.

OBJECTIVE To identify risk factors for first-onset congestive heart failure (CHF) in dogs with degenerative mitral valve disease (DMVD). ANIMALS Eighty-two dogs with and without CHF secondary to DMVD were retrospectively assigned to a derivation cohort. Sixty-five dogs with asymptomatic DMVD were recruited into a prospective validation cohort. METHODS Variables associated with risk of CHF in dogs were identified in a derivation cohort and used to construct a predictive model, which was then prospectively tested through longitudinal examination of a validation cohort. RESULTS Logistic regression analysis of the derivation cohort yielded a predictive model that included the left atrial to aortic root dimension ratio (LA:Ao) and plasma concentration of N-terminal pro-B-type natriuretic peptide (NT-proBNP). When this model was prospectively applied to the validation cohort, it correctly predicted first-onset of CHF in 69.2% of cases. Analysis of the validation cohort revealed that plasma NT-proBNP concentration and indexed left ventricular end-diastolic diameter (LVIDd:Ao) were independent risk factors for development of first-onset CHF in dogs with DMVD (NT-proBNP ≥ 1500 pmol/L, odds ratio (OR), 5.76, 95% confidence interval (CI), 1.37-24.28, P = 0.017; LVIDd:Ao ≥ 3, OR, 6.11, 95% CI, 1.09-34.05, P = 0.039). CONCLUSIONS Measures of left heart size and plasma NT-proBNP concentration independently estimate risk of first-onset of CHF in dogs with DMVD. These parameters can contribute to the management of dogs with DMVD.

Prospective Evaluation of Two Intracorporeally Sutured Prophylactic Laparoscopic Gastropexy Techniques Compared with Laparoscopic-Assisted Gastropexy in Dogs

OBJECTIVE To report technique, surgical time, complication rate, and postoperative activity in dogs undergoing 2 intracorporeally-sutured total laparoscopic gastropexy (TLG) techniques compared with a laparoscopic-assisted gastropexy (LAG) technique. STUDY DESIGN Randomized clinical trial. ANIMALS Dogs (n=30) weighing >25 kg. METHODS Dogs were randomly assigned to 1 of 3 groups. Two TLG techniques were performed using a median 3 portal technique. One of 2 suturing techniques was used to approximate corresponding incisions made in the stomach and body wall; using intracorporeal hand-suturing or a suture-assist device (Endostitch). In a 3rd group, a previously reported LAG technique was used. All dogs had an activity monitor placed for 7 days pre- and postoperatively. Linear regression analyses were performed to evaluate the association of surgical procedure on gastropexy time and the percentage change in activity counts. RESULTS Median gastropexy time was 28 minutes (range, 20-41 minutes) for LAG, 48 minutes (range, 39-61 minutes) for the hand suture TLG technique, and 56 minutes (range, 30-90 minutes) for the Endostitch TLG technique. LAG was performed faster than TLG (P<.05). LAG dogs had a greater decrease in postoperative activity than TLG dogs (P=.005); however there was no difference in surgical time or postoperative activity between TLG techniques. CONCLUSIONS TLG can be performed safely and effectively in dogs and although it takes longer, it has less impact on postoperative activity compared with LAG. CLINICAL RELEVANCE TLG techniques may have advantages over LAG as measured by a greater willingness of dogs to move around postoperatively.

Comparison of surgical site infection rates in clean and clean-contaminated wounds in dogs and cats after minimally invasive versus open surgery: 179 cases (2007–2008)

OBJECTIVE To report and compare the surgical site infection (SSI) rates for clean and clean-contaminated procedures performed by either a minimally invasive surgical or open surgical approach in a large population of dogs and cats. DESIGN Prospective case series. ANIMALS 179 patients (dogs and cats) undergoing minimally invasive abdominal or thoracic surgery. PROCEDURES Case information from all animals that underwent minimally invasive abdominal or thoracic surgery was prospectively collected and compared with an existing database of the same information collected from 379 patients undergoing laparotomy or thoracotomy via an open surgical approach. For both groups, an SSI was defined as any surgical wound in which purulent discharge was observed within 14 days after the procedure. Follow-up for all patients was obtained by direct examination or telephone interviews. RESULTS Overall SSI rate in the minimally invasive surgery (MIS) group was 1.7% and in the open surgery (OS) group was 5.5%. On univariate analysis, there was a significantly lower SSI rate in the MIS group, compared with the SSI rate for the OS group. On multivariable logistic regression analysis, this difference appeared to be a result of the fact that surgery times were longer (median, 105 vs 75 minutes) and hair was clipped ≥ 4 hours prior to surgery for more animals (23% vs 11 %) in the OS group, compared with the MIS group. CONCLUSIONS AND CLINICAL RELEVANCE MIS may be associated with a lower SSI rate, compared with OS, but confounding factors such as differences in surgery time and preoperative preparation contributed in part to this finding. As such, surgical approach cannot be categorized as an independent risk factor for SSIs in small animals until further studies are performed.

Use of an activity monitor to detect response to treatment in dogs with osteoarthritis

OBJECTIVE To determine whether an activity monitor (AM) could be used to detect changes in activity in dogs with osteoarthritis treated with carprofen or a placebo. DESIGN Randomized controlled trial. ANIMALS 70 dogs with no clinically important abnormalities other than osteoarthritis for which they were not currently being treated. PROCEDURES Dogs wore an AM continuously for 21 days. On days 8 through 21, the dogs were treated with carprofen (n = 35) or a placebo (35). Total activity counts for days 1 through 7 (baseline) were compared with total activity counts for days 15 through 21 (endpoint). The change in total activity count from baseline to endpoint was assessed within each treatment group as well as between groups. Linear regression analysis was performed to test for an association between treatment and percentage change in activity counts while controlling for other variables. RESULTS For placebo-treated dogs, median baseline total activity count was not significantly different from median endpoint total activity count (1,378,408 vs 1,310,112, respectively). For dogs receiving carprofen, there was a significant increase in median activity count from baseline to endpoint (1,276,427 vs 1,374,133). When age and baseline activity counts were controlled for, dogs in the carpofen-treated group had a 20% increase in activity counts, compared with placebo-treated dogs (95% confidence interval, 10% to 26%). CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that the AM used in the present study may be a valid outcome assessment tool for documenting improved activity associated with treatment in dogs with osteoarthritis.

Comparison of Force Plate Gait Analysis and Owner Assessment of Pain Using the Canine Brief Pain Inventory in Dogs with Osteoarthritis

BACKGROUND Lameness assessment using force plate gait analysis (FPGA) and owner assessment of chronic pain using the Canine Brief Pain Inventory (CBPI) are valid and reliable methods of evaluating canine osteoarthritis. There are no studies comparing these 2 outcome measures. OBJECTIVE Evaluate the relationship between CBPI pain severity (PS) and interference (PI) scores with the vertical forces of FPGA as efficacy measures in canine osteoarthritis. ANIMALS Sixty-eight client-owned dogs with osteoarthritis (50 hind limb and 18 forelimb). METHODS Double-blind, randomized. Owners completed the CBPI, and dogs underwent FPGA on days 0 and 14. Dogs received carprofen or placebo on days 1 through 14. The change in PS and PI scores from day 0 to 14 were compared to the change in peak vertical force (PVF) and vertical impulse (VI). RESULTS PS and PI scores significantly decreased in carprofen- compared with placebo-treated dogs (P = .002 and P = .03, respectively). PVF and VI significantly increased in carprofen- compared with placebo-treated dogs (P = .006 and P = .02, respectively). There was no correlation or concordance between the PS or PI score changes and change in PVF or VI. CONCLUSIONS AND CLINICAL IMPORTANCE In these dogs with hind limb or forelimb osteoarthritis, owner assessment of chronic pain using the CBPI and assessment of lameness using FPGA detected significant improvement in dogs treated with carprofen. The lack of correlation or concordance between the change in owner scores and vertical forces suggests that owners were focused on behaviors other than lameness when making efficacy evaluations in their dogs.

Gall bladder mucoceles and their association with endocrinopathies in dogs: a retrospective case-control study

OBJECTIVE To investigate the relationship between endocrinopathies and diagnosis of gall bladder mucocele in dogs via a retrospective case-control study. METHODS Records of 78 dogs with a surgical or ultrasonographic diagnosis of gall bladder mucocele were examined for the presence or absence of hyperadrenocorticism, hypothyroidism and diabetes mellitus. Two age- and breed-matched controls for each gall bladder mucocele dog (156 total control dogs) were examined for the same concurrent diseases. A matched case-control analysis was performed using conditional logistic regression. RESULTS The odds of mucocele in dogs with hyperadrenocorticism were 29 times that of dogs without hyperadrenocorticism (P=0.001; 95 per cent CI 3.8, 219.9). No difference was found between dogs with and without diabetes mellitus. Although a significant association was found between gall bladder mucocele and hypothyroidism, potential observation bias was also identifi ed. CLINICAL SIGNIFICANCE Hyperadrenocorticoid dogs that were presented for acute illness with laboratory evidence of hepatobiliary disease should undergo evaluation for the presence of a biliary mucocele. Dogs diagnosed with a gall bladder mucocele should be screened for concurrent hyperadrenocorticism if clinical suspicion exists.