Treatment of oral squamous cell carcinoma with accelerated radiation therapy and concomitant carboplatin in cats

Background: Feline oral squamous cell carcinoma (SCC) carries a very poor prognosis with traditional treatments. Hypothesis/Objectives: To examine the effectiveness of adding carboplatin to a previously published accelerated radiation protocol in the treatments of oral SCC in cats. Animals: Thirty‐one cases of oral SCC in cats. Tumor sites included lingual (n = 9), mandible (n = 10), maxilla (n = 7), tonsil (n = 4), and cheek (n = 1). Methods: Prospective trial using a planned radiation protocol consisting of 14 fractions of 3.5 Gy given within a 9‐day period with the addition of carboplatin given at 90–100 mg/m² on day 1 and day 4.5. Treatments were twice daily with a 6‐hour delay between treatments. All cats presenting with oral SCC without evidence of distant metastasis were eligible. Results: Median survival for all cats was 163 days (range 53–770 days) with a mean of 319 ± 53 days with significant predictors of survival being site (P= .004) and whether there was a complete response at 30 days (P= .001). Cats with tumors of tonsil origin or cheek responded best to therapy and were long‐term survivors with a mean survival of 724 days and the median had not been reached because of continued survival of 4 cats. Conclusions and Clinical Importance: This protocol offers an aggressive yet tolerable treatment of oral SCC in cats that might offer improved survival as compared with previously reported treatments. The long‐term survival of cats with tonsillar SCC has not been reported previously.     

Quantification of plasma DNA as a prognostic indicator in canine lymphoid neoplasia

Dogs have a similar incidence of spontaneous cancers as people, and a noninvasive test to monitor disease status in dogs would be of great value. Humans with cancer often have increased levels of cell‐free circulating DNA in their plasma, which has shown promise for diagnosis, prognosis and detection of residual disease. We hypothesized that dogs with cancer have increased circulating DNA compared with healthy dogs or dogs with non‐neoplastic diseases. Plasma DNA was measured in 40 healthy dogs, 20 dogs with non‐neoplastic diseases and 80 dogs with cancer. The reference interval for plasma DNA in healthy dogs was 1–15 ng mL^?1. Dogs with lymphoma and lymphoid leukaemia had significantly higher concentrations (range: 0–91 ng mL^?1, P < 0.0001). Antigen receptor rearrangement assays suggest that plasma DNA had the same clonality as the primary lymphoid tumours. Dogs with lymphoid neoplasia and plasma DNA >25 ng mL^?1 had shorter remission times than those with < 25 ng mL^?1 (P= 0.0116). In contrast to humans, where increased plasma DNA is seen in many diseases, dogs with nonlymphoid malignancies and non‐neoplastic diseases had plasma DNA concentrations similar to healthy dogs. This study shows that a portion of dogs with lymphoid neoplasia have increased tumour‐derived plasma DNA, which serves as a negative prognostic indicator.     

Evaluation of dexamethasone as a chemoprotectant for CCNU‐induced bone marrow suppression in dogs*

In mice and people, administering corticosteroids before chemotherapy can reduce the severity of myelosuppression without reducing antitumour effects. This study investigated whether pretreatment with dexamethasone would reduce the incidence of grade 4 neutropenia in dogs receiving CCNU. Twenty‐five dogs received dexamethasone [0.1 mg kg^?1 per os (PO) every 12 h] for 5 days and on the sixth day received CCNU (90 mg m^?2 PO). Historical dogs (n = 67) received CCNU alone (90 mg m^?2 PO). Forty‐five percent of historical dogs had grade 4 neutropenia, while 64% of dogs pretreated with dexamethasone had grade 4 neutropenia (P = 0.16). Dexamethasone plasma levels were quantified by enzyme‐linked immunosorbent assay in three healthy dogs. Peak plasma concentrations after a single oral 0.1‐mg kg^?1 dose were <80 ng mL^?1, the minimum level associated with chemoprotective effects of dexamethasone in people. Pretreatment with dexamethasone did not reduce the incidence of grade 4 neutropenia in dogs receiving CCNU.     

Urinary aldosterone to creatinine ratio in cats before and after suppression with salt or fludrocortisone acetate

Background: The endocrine diagnosis of primary hyperaldosteronism in cats currently is based on an increased plasma aldosterone to renin ratio, which has several disadvantages for use in veterinary practice. Objectives: To establish a reference range for the urinary aldosterone to creatinine ratio (UACR) and to determine whether oral administration of either sodium chloride or fludrocortisone acetate is effective for use in a suppression test. Animals: Forty‐two healthy cats from an animal shelter and 1 cat with primary hyperaldosteronism from a veterinary teaching hospital. Methods: Morning urine samples for determination of the basal UACR were collected from 42 healthy cats. For the suppression tests, urine samples for the UACR were collected after twice daily oral administration for 4 consecutive days of either sodium chloride, 0.25 g/kg body weight (n = 22) or fludrocortisone acetate, 0.05 mg/kg body weight (n = 15). Results: The median basal UACR was 7.2 × 10^?9 (range, 1.8–52.3 × 10^?9), with a calculated reference range of <46.5 × 10^?9. Administration of sodium chloride resulted in adequate salt loading in 10 of 22 cats, but without significant reduction in the UACR. Administration of fludrocortisone resulted in a significant decrease in the UACR (median, 78%; range, 44–97%; P < .001) in healthy cats. In the cat with an aldosterone‐producing adrenocortical carcinoma, the basal UACR and the UACR after fludrocortisone administration were 32 × 10^?9 and 36 × 10^?9, respectively. Conclusions and Clinical Importance: Using the UACR for an oral fludrocortisone suppression test may be useful for the diagnosis of primary hyperaldosteronism in cats.     

Toxicity and outcome in cats with oral squamous cell carcinoma after accelerated hypofractionated radiotherapy and concurrent systemic treatment

Recently, a multimodal approach to oral squamous cell carcinoma (SCC) in cats, combining medical treatment and accelerated radiation therapy, showed a substantial outcome improvement in a small pilot study. Herein we retrospectively review 51 cats with unresectable, histologically confirmed oral SCC and a complete initial staging work‐up: cats in group A (n = 24) received medical anti‐angiogenic treatment consisting of bleomycin, piroxicam and thalidomide, cats in group B (n = 27) received the anti‐angiogenic treatment and concurrent accelerated hypofractionated radiation therapy with 48Gy delivered in 10 fractions. Overall median progression‐free interval (PFI) was poor with 70 days (95% CI: 48;93). In the irradiated cats (group B), however, PFI was significantly longer with 179 days (95% CI: 58;301) days, vs 30 days (95% CI: 23;38) in medically only treated cats (P < .001). Overall median overall survival (OS) was 89 days (95% CI: 55;124), again significantly longer in the irradiated cats (group B) with 136 (95% CI: 40;233) vs 38 days (95% CI: 23;54) (P < .001). In 8 of the 27 (29.6%) cats in group B, however, severe toxicity (grade 3) occurred. Neither onset nor severity of toxicity could be associated with any of the tested variables, including anatomic site, tumour size, clinical stage and duration of neoadjuvant medical treatment. Given the potential severe acute effects and the impact on quality of life after chemo‐radiotherapy, owners must be clearly informed about the risks of treatment. With the overall poor outcome and high occurrence of acute toxicity, we cannot recommend the use of this accelerated radiation protocol combined with anti‐angiogenic therapy for oral SCC in cats.     

PALLIATIVE RADIATION THERAPY OUTCOMES FOR CATS WITH ORAL SQUAMOUS CELL CARCINOMA (1999–2005)

Squamous cell carcinoma (SCC) accounts for approximately 10% of all feline tumors. The purpose of this retrospective study was to describe outcomes for a group of cats with oral SCC that were treated with palliative radiation therapy. Fifty‐four cats met the inclusion criteria of nonresectable, oral SCC treated with coarse fractionated megavoltage (MeV) radiation therapy. Radiation therapy for all cats was delivered with a 6 MeV linear accelerator. Total radiation doses of 24 Gray to 40 Gray were administered in three to four fractions, once‐per‐week over 4 to 5 weeks. Concurrent chemotherapy protocols varied and were administered at the discretion of the clinician and client. Forty‐nine patients completed the planned treatment protocols. Overall mean and median survival times for cats completing the planned treatment protocols were 127 and 92 days (n = 49). Mean and median survival times of cats receiving palliative radiation therapy alone were 157 and 113 days (n = 12). Mean and median survival times of patients receiving both radiation therapy and chemotherapy were 116 and 80 days (n = 37). Patients with sublingual tumors had a median survival time of 135 days (n = 15), compared to mandibular tumors that had a median survival time of 80 days (n = 26). For the majority of patients that completed the planned treatment protocol (65%), owners reported a subjectively improved quality of life. Findings from this uncontrolled study supported the use of palliative radiation therapy for cats with nonresectable oral squamous cell carcinoma.     

Plasma homocysteine, B vitamins, and amino acid concentrations in cats with cardiomyopathy and arterial thromboembolism

Arterial thromboembolism (ATE) is a common complication of cats with cardiomyopathy (CM), but little is known about the pathophysiology of ATE. In people, high plasma concentrations of homocysteine and low B vitamin concentrations are risk factors for peripheral vascular disease. In addition, low plasma arginine concentrations have been linked to endothelial dysfunction. The purpose of this study was to compare concentrations of homocysteine, B vitamins, and amino acids in plasma of normal cats to those of cats with CM and ATE. Plasma concentrations of homocysteine, vitamin B6, vitamin B12, folate, and amino acids were measured in 29 healthy cats, 27 cats with CM alone, and 28 cats with both CM and ATE. No differences were found between groups in homocysteine or folate. Mean vitamin B12 concentration (mean +/- standard deviation) was lower in cats with ATE (866 +/- 367 pg/mL) and cats with CM (939 +/- 389 pg/mL) compared with healthy controls (1,650 +/- 700 pg/mL; P < .001). Mean vitamin B6 concentration was lower in cats with ATE (3,247 +/- 1.215 pmol/mL) and cats with CM (3,200 +/- 906 pmol/mL) compared with healthy control animals (4,380 +/- 1,302 pmol/mL; P = .005). Plasma arginine concentrations were lower in cats with ATE (75 +/- 33 nmol/mL) compared with cats with CM (106 +/- 25 nmol/mL) and healthy control animals (96 +/- 25 nmol/ mL; P < .001). Vitamin B12 concentration was significantly correlated with left atrial size. We interpret the results of this study to suggest that vitamin B12 and arginine may play a role in CM and ATE of cats.     

Pharmacokinetics of posaconazole in koalas (Phascolarctos cinereus) after intravenous and oral administration

The pharmacokinetic profile of posaconazole in clinically normal koalas (n = 8) was investigated. Single doses of posaconazole were administered intravenously (i.v.; 3 mg/kg; n = 2) or orally (p.o.; 6 mg/kg; n = 6) with serial plasma samples collected over 24 and 36 hr, respectively. Plasma concentrations of posaconazole were quantified by validated high‐performance liquid chromatography. A noncompartmental pharmacokinetic analysis of data was performed. Following i.v. administration, estimates of the median (range) of plasma clearance (CL) and steady‐state volume of distribution (V_ss) were 0.15 (0.13–0.18) L hr^?1 kg^?1 and 1.23 (0.93–1.53) L/kg, respectively. The median (range) elimination half‐life (t_1/2) after i.v. and p.o. administration was 7.90 (7.62–8.18) and 12.79 (11.22–16.24) hr, respectively. Oral bioavailability varied from 0.43 to 0.99 (median: 0.66). Following oral administration, maximum plasma concentration (C_max; median: 0.72, range: 0.55–0.93 μg/ml) was achieved in 8 (range 6–12) hr. The in vitro plasma protein binding of posaconazole incubated at 37°C was 99.25 ± 0.29%. Consideration of posaconazole pharmacokinetic/pharmacodynamic (PK/PD) targets for some yeasts such as disseminated candidiasis suggests that posaconazole could be an efficacious treatment for cryptococcosis in koalas.     

Comparison of the pharmacokinetics and thermal antinociceptive pharmacodynamics of 20 µg kg−1 buprenorphine administered sublingually or intravenously in cats

Little is known about the analgesic action of buprenorphine (BUP) in cats. Relative to man, the cat has a more alkaline oral pH, which may make this an effective route for administering BUP in this species. This study aimed to assess and compare the pharmacokinetics and pharmacodynamics of sublingual (S‐L) and IV administration of BUP. Thermal threshold (TT) was measured and blood samples were collected following IV or S‐L administration (20 µg kg^?1) of the injectable formulation. Six cats (five spayed females, one castrated male, 4.1–6.6 kg) were used. Each cat received both treatments in a randomized cross‐over study design with 1 month between experiments. Twenty‐four hours prior to each study, the lateral thorax of each of the cats was shaved, cephalic and jugular catheters placed, and oral pH measured. On the day of the study, TT was measured using a ‘thorax‐mounted’ thermal threshold‐testing device specifically developed for cats. The cats were free to move around. Skin temperature was recorded before each test, then the heater activated. When the cat responded by flinching, turning, or jumping, the stimulus was terminated and the threshold temperature was recorded. The thermal threshold cut‐off point was 55.5 °C. Three baseline thresholds were recorded before treatment with S‐L or IV (via cephalic catheter) BUP (20 µg kg^?1). Blood was withdrawn (jugular) at 1, 2, 4, 6, 10, 15, 30, 45, 60 minutes and at 2, 4, 6, 8, 12, and 24 hours post‐administration. TT was measured every 30 minutes?6 hours, 1–12 hours, and at 24 hours post‐administration. Plasma was immediately separated, stored at ?20.5 °C, and assayed within 4 months using a commercially available ¹²⁵I radioimmunoassay. Threshold data were analyzed using anova with a repeat factor of time. No adverse effects were noted. Pupils were dilated for up to 9 hours post‐BUP. Behavioral changes were calm euphoria. Measured oral pH was 9 in each cat. Pre‐treatment mean threshold (±SD) was 41.2 ± 0.9 °C in the S‐L group and 40.8 ± 0.85 °C in the IV group. There were no significant differences between the groups with respect to thresholds over time (p = 0.72). Thresholds were significantly increased from 30 to 360 minutes in both the groups (>44.615 °C). Peak plasma BUP (C_max) was lower (11 ± 6.7 ng mL^?1vs. 92.9 ± 107.9 ng mL^?1) and occurred later (T_max) (30 minutes vs. 1 minute) after S‐L compared to IV administration, respectively. BUP (20 µg kg^?1)‐administered S‐L or IV provided antinociception between 30 and 360 minutes after administration. Plasma levels did not correspond to TT.     

Epidemiological,pathological and immunohistochemical aspects of 125 cases of feline lymphoma in Southern Brazil

A retrospective study compiling cases of feline lymphoma diagnosed during 12 years (2004‐2016) in Southern Brazil was performed. A total of 125 cases of lymphoma diagnosed in cats were reviewed, and information including age, breed, sex and tumour topography were collected. FeLV and FIV immunohistochemical tests were performed, as well as immunophenotyping of lymphomas. The alimentary form represented the most common presentation (42/125), followed by mediastinal lymphoma (35/125). Out of 125 cases, 79 presented positive retroviral immunostaining in tumour tissue (52 FeLV alone, 14 FIV alone and 13 presented FIV and FeLV co‐infections), 66/125 of the cases were of T‐cell origin and 59/125 of the cases were of B‐cell origin. The median age of cats with T‐cell lymphoma was 120 months (10‐240 months), and 60 months (6‐204 months) for cats with B‐cell lymphoma. The most frequent alimentary tumour presentation was the enteropathy‐associated T‐cell lymphoma (type 1), and the major type of mediastinal tumour observed was diffuse large B‐cell lymphoma. Considering only mediastinal and alimentary lymphomas (n = 77), the prevalence of mediastinal lymphoma in FeLV‐positive cats was 2.21 times higher than the prevalence of this type of tumour in FeLV‐negative cats (P = .036). Mediastinal lymphoma was more frequently observed in younger cats, and the prevalence of mediastinal tumours in these animals was 3.06 times higher than the prevalence of this tumour form in old cats (P = .0125). The present study indicates that retroviral infections still play an important role in the development of feline lymphomas in southern Brazil.     

Assessment of predictive molecular variables in feline oral squamous cell carcinoma treated with stereotactic radiation therapy

This study evaluated molecular characteristics that are potentially prognostic in cats with oral squamous cell carcinoma (SCC) that underwent stereotactic radiation therapy (SRT). Survival time (ST) and progression‐free interval (PFI) were correlated with mitotic index, histopathological grades, Ki67 and epidermal growth factor receptor expressions, tumour microvascular density (MVD), and tumour oxygen tension (pO₂). Median ST and PFI were 106 and 87 days, respectively (n = 20). Overall response rate was 38.5% with rapid improvement of clinical symptoms in many cases. Patients with higher MVD or more keratinized SCC had significantly shorter ST or PFI than patients with lower MVD or less keratinized SCC (P = 0.041 and 0.049, respectively). Females had significantly longer PFI and ST than males (P ≤ 0.016). Acute toxicities were minimal. However, treatment‐related complications such as fractured mandible impacted quality of life. In conclusion, SRT alone should be considered as a palliative treatment. MVD and degree of keratinization may be useful prognostic markers.     

Intravenous regional anesthesia in isoflurane anesthetized cats: lidocaine plasma concentrations and cardiovascular effects

Objective To determine if intravenous regional anesthesia (IVRA) can be used in cats without resulting in excessive plasma lidocaine concentrations or adverse cardiovascular effects. Study design Prospective, blinded crossover study. Animals Seven healthy male young adult cats weighing 3.96 ± 0.63 kg. Methods At 2.3% end‐tidal isoflurane concentration, lidocaine (L) 3 mg kg^?1 (1%) or saline (S) was injected in a distal cephalic venous catheter after application of two tourniquets to that forelimb which remained in place for 20 minutes. Heart and respiratory rates, arterial blood pressures and ECG were recorded every 5 minutes during tourniquet application and for 20 minutes following tourniquet removal. Lidocaine plasma concentrations were measured 5 minutes after injection and 0.5, 1, 2, 4, 8, 20 and 40 minutes after tourniquet removal. End tidal isoflurane concentrations were reduced to 1.5–2.0% to elicit a response to toe pinch (RTP) in the contralateral leg. The study was repeated similarly in the contralateral leg and RTP was graded for 40 minutes. Response was also tested in the leg previously injected, the differences between the two scores determined and those differences compared between the L and S treatments. The data were analyzed using anova for repeated measures comparing values to baseline. Significance was set at p < 0.005 using the Bonferroni method for multiple comparisons. Results There were no significant differences in physiologic parameters at either isoflurane concentration. Differences in RTP were significantly larger in the lidocaine treatment. The highest mean lidocaine concentrations were measured 0.5 minutes after tourniquet removal after both injections and were 2.79 ± 1.05 and 3.10 ± 1.11 µg mL^?1. The highest individual plasma concentration was 6.46 µg mL^?1. Conclusion No adverse hemodynamic effects were evident after IVRA lidocaine in any cat. The lidocaine dose studied inhibited a RTP until 20 minutes after tourniquet removal. Lidocaine concentrations varied and were measurable prior to tourniquet removal. Clinical relevance IVRA may be a suitable technique for cats undergoing surgery of the distal limbs.     

Determination of carcinoembryonic antigen and cancer antigen (CA 15‐3) in bitches with tumours on mammary gland: preliminary report

The aim of this work was to determine levels of carcinoembryonic antigen (CEA) and cancer antigen (CA 15‐3) in the blood serum of 45 bitches. A modified procedure was used to determine the CEA and CA 15‐3 markers with the human kits using the radioimmunoassay method. Samples collected from extirpated tumour of mammary glands were histologically processed and classified as per WHO guidelines. The average age of animals with tumour was 10.00 ± 2.2 years; for healthy bitches average age was 4.2 ± 3.2 years. Values of CEA and CA 15‐3 were considered positive, if they exceeded 0.23 ng mL^?1 and 7 IU mL^?1, respectively. Average levels of CEA in the tumour group were 0.25 ± 0.06 versus 0.20 ± 0.03 in healthy bitches (P = 0.0001). The average CA 15‐3 value in bitches with tumour was 8.58 ± 1.27 versus 5.14 ± 1.34 in healthy animals (P < 0.0001).     

Serum 25‐hydroxyvitamin D concentrations in dogs – correlation with health and cancer risk

25‐hydroxyvitamin D (25(OH)D) is important in bone health as well as many diseases including cancer. Supplementation may increase responsiveness of cancer cells to chemotherapy. Serum 25(OH)D, intact parathyroid hormone (iPTH) and canine C‐reactive protein (c‐CRP) were measured in healthy dogs and dogs with haemoabdomen. Regression analysis determined optimal 25(OH)D concentrations. In healthy dogs (n = 282), mean iPTH concentrations correlated inversely (r² = 0.88, P < 0.001) to 25(OH)D concentrations. Variation in both iPTH and c‐CRP plateaued at 25(OH)D concentrations of 100–120 ng mL^?1. Haemoabdomen dogs (n = 63, 43 malignant and 20 benign) had 25(OH)D concentrations ranging from 19.4 to >150 ng mL^?1. Relative risk of cancer increased with decreasing 25(OH)D concentrations [RR = 3.9 for 25(OH)D below 40 ng mL^?1 (P = 0.0001)]. Serum 25(OH)D concentrations in dogs vary widely, and are influenced by dietary VitD content. Serum vitD measurement can identify dogs for which supplementation may improve health and response to cancer therapy.     

Pharmacokinetics of the novel COX‐2 selective inhibitor vitacoxib in cats: The effects of feeding and dose

The purpose of this study was to determine the pharmacokinetics and dose‐scaling model of vitacoxib in either fed or fasted cats following either oral or intravenous administration. The concentration of the drug was quantified by UPLC‐MS/MS on plasma samples. Relevant parameters were described using noncompartmental analysis (WinNonlin 6.4 software). Vitacoxib is relatively slowly absorbed and eliminated after oral administration (2 mg/kg body weight), with a T_max of approximately 4.7 hr. The feeding state of the cat was a statistically significant covariate for both area under the concentration versus time curve (AUC) and mean absorption time (MAT_fed). The absolute bioavailability (F) of vitacoxib (2 mg/kg body weight) after oral administration (fed) was 72.5%, which is higher than that in fasted cats (F = 50.6%). Following intravenous administration (2 mg/kg body weight), Vd (ml/kg) was 1,264.34 ± 343.63 ml/kg and Cl (ml kg^?1 hr^?1) was 95.22 ± 23.53 ml kg^?1 hr^?1. Plasma concentrations scaled linearly with dose, with C_max (ng/ml) of 352.30 ± 63.42, 750.26 ± 435.54, and 936.97 ± 231.27 ng/ml after doses of 1, 2, and 4 mg/kg body weight, respectively. No significant undesirable behavioral effects were noted throughout the duration of the study.     

RESEARCH PAPER: Incidence of elevation of cardiac troponin I prior to and following routine general anaesthesia in dogs

ObjectiveTo estimate the incidence of raised cTnI after general anaesthesia in dogs and to explore major risk factors influencing this.Study designProspective clinical study.AnimalsA total of 107 (ASA physical status 1?2) dogs, 63% male and 37% female, median age 5 years (range 0.3–13.4), median weight 24.4 kg (range 4.2–66.5 kg) undergoing anaesthesia for clinical purposes.MethodsVenous blood samples were taken within 24 hours prior to induction and 24 hours after the termination of anaesthesia. Serum concentrations of cardiac troponin I were measured using a chemiluminescent enzyme immunometric assay with a lower level of detection of 0.20 ng mL^?1 (below this level <0.20 ng mL^?1). Continuous data were assessed graphically for normality and paired and unpaired data compared with the Wilcoxon signed ranks and Mann–Whitney U‐tests respectively. Categorical data were compared with the Chi squared or Fisher’s exact test as appropriate (p < 0.05).ResultsOf the 107 dogs recruited, 100 had pre‐ and post‐anaesthetic cTnI measured. The median pre‐anaesthesia cTnI was ‘<0.20’ ng mL^?1 (range ‘<0.20’–0.43 ng mL^?1) and the median increase from pre‐anaesthesia level was 0.00 ng mL^?1 (range ?0.12 to 0.61 ng mL^?1). Fourteen dogs had increased cTnI after anaesthesia relative to pre‐anaesthesia (14%, 95% CI 7.2–20.8%, range of increase 0.03–0.61 ng mL^?1). Six animals had cTnI levels that decreased (range 0.02–0.12 ng mL^?1). Older dogs were more likely to have increased cTnI prior to anaesthesia (OR = 5.32, 95% CI 1.35–21.0, p = 0.007) and dogs 8 years and over were 3.6 times as likely to have an increased cTnI after anaesthesia (95% CI 1.1–12.4, p = 0.028).Conclusion and clinical relevanceIncreased cTnI after anaesthesia relative to pre‐anaesthesia levels was observed in a number of apparently healthy dogs undergoing routine anaesthesia.     

Expression of vascular endothelial growth factor in canine oral malignant melanoma

Serum, plasma and tissue expression of vascular endothelial growth factor (VEGF) was measured in 20 dogs previously diagnosed histologically with oral melanoma. The concentrations of VEGF in serum and plasma were significantly higher in dogs with melanoma than in a control population (P ≤ 0.002). Concentrations of VEGF in the serum and plasma of dogs with melanoma were highly correlated (r = 0.867). Ninety‐five per cent of melanoma tissues expressed VEGF. Two staining patterns were detected: diffuse and granular cytoplasmic staining. High blood concentrations of VEGF were correlated to a shorter survival time in dogs receiving definitive therapy (P = 0.002). Survival times were significantly longer in dogs receiving definitive therapy versus palliative therapy (median 496 versus 97 days, P = 0.007). Blood concentrations of VEGF were associated with stage (P < 0.05). Dogs with oral melanoma have increased serum, plasma and tissue concentrations of VEGF. Increased expression of VEGF may be a reasonable target for future therapy of canine oral melanoma.     

Effects of intravenous lidocaine on the minimum alveolar concentration of isoflurane in cats

Lidocaine has been reported to decrease the minimum alveolar concentration (MAC) of inhalation anesthetics in several species and has been used clinically to reduce the requirements for other anesthetic drugs. This study examined the effects of intravenous lidocaine on isoflurane MAC in cats. Six cats were studied. In experiment 1, the MAC of isoflurane was determined. An intravenous bolus of lidocaine 2 mg kg^–1 was then administrated and venous plasma lidocaine concentrations measured to determine pharmacokinetic values. In experiment 2, lidocaine was administered to achieve target plasma concentrations between 1 and 11 μg mL^–1 and the MAC of isoflurane was determined in triplicate at each lidocaine plasma concentration, using the tail‐clamp method. End‐tidal isoflurane concentration was determined using a calibrated infrared analyzer. Systolic blood pressure (Doppler), SpO2 and end‐tidal PCO2 (calibrated Raman spectrometer) were measured prior to each MAC determination. Body temperature was maintained between 38.5 and 39.5 °C by supplying external heat as needed. MAC values at the different lidocaine plasma concentrations were analyzed by a repeated measures ANOVA , using the Huynh–Feldt correction. The MAC of isoflurane in these cats was 2.21 ± 0.17. For the target concentrations of 1, 3, 5, 7, 9, and 11 μg mL^–1, the actual lidocaine plasma concentrations was 1.06 ± 0.12, 2.83 ±0.39, 4.93 ± 0.64, 6.86 ± 0.97, 8.86 ± 2.10, and 9.84 ± 1.34 μg mL^–1, respectively. At these target concentrations, the MAC of isoflurane was 2.14 ± 0.14, 1.88 ± 0.18, 1.66 ± 0.16, 1.47 ±0.13, 1.33 ± 0.23, and 1.06 ± 0.19%, respectively. Lidocaine, at target plasma concentrations of 1, 3, 5, 7, 9, and 11 μg mL^–1, linearly decreased isoflurane MAC by –6 to 6, 7 to 28, 19 to 35, 28 to 45, 29 to 53, and 44 to 59%, respectively. Lidocaine significantly dose‐dependently and linearly decreases the requirements for isoflurane in cats. No ceiling effect was observed within the range of plasma concentrations studied.     

Utility of measuring plasma N-terminal pro-brain natriuretic peptide in detecting hypertrophic cardiomyopathy and differentiating grades of severity in cats

Background: Cats with hypertrophic cardiomyopathy (HCM) often have no clinical signs or subtle signs. Measurement of N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) has been demonstrated in people to be highly specific for heart disease and also correlates with severity of HCM. NT‐proBNP may also be valuable in detecting and grading HCM in cats, but results to date have been equivocal. Objectives: The aims of this study were to evaluate NT‐proBNP as a screening test for diagnosis of HCM in cats and determine an appropriate cut‐off value and to determine if NT‐proBNP concentrations correlated with severity of HCM in cats. Methods: Plasma NT‐proBNP concentrations were measured in 201 cats using an ELISA designed for use in cats. Cats were classified using echocardiography as clinically healthy controls (n=99) or cats with equivocal (n=9), mild (n=15), moderate (n=17), or severe (n=61) HCM. Results: NT‐proBNP concentrations (median; 25th–75th interquartile percentiles) in mildly (216.1; 87.6–392.5 pmol/L), moderately (282.7; 131.9–466.6 pmol/L), and severely (839.5; 655.3–1046.4 pmol/L) affected cats were significantly higher than those in healthy controls (18.9; 3.4–62.4 pmol/L). Concentrations in severely affected cats were significantly higher than in cats from other HCM groups. There was no significant difference between mild and moderate HCM. Cut‐off values >49 pmol/L had a sensitivity of 97.8% and specificity of 66.7%; >100 pmol/L had a sensitivity of 92.4% and specificity of 93.9%; and >150 pmol/L had a sensitivity of 88% and a specificity of 100%. Conclusions: NT‐proBNP with a cut‐off value of >100 pmol/L was useful in detecting even mild HCM. Cats with increased NT‐proBNP concentrations should be examined by echocardiography.     

Pharmacokinetics of single-dose oral pregabalin administration in normal dogs

ObjectiveTo describe the pharmacokinetics of pregabalin in normal dogs after a single oral dose.Study designProspective experiment.AnimalsSix adult Labrador/Greyhound dogs (four females and two males) aged 2.6 (2.6–5.6) years old (median and range) weighing 33.4 (26.8–42.1) kg.MethodsAfter jugular vein catheterization, the dogs received a single oral dose of pregabalin (～4 mg kg^?1). Blood samples were collected at: 0 (before drug administration), 15 and 30 minutes and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 36 hours after drug administration. Plasma pregabalin concentration was measured by HPLC. Noncompartmental analysis was used to estimate pharmacokinetic variables.ResultsNo adverse effects were observed. The median (range) pharmacokinetic parameters were: Area under the curve from time 0 to 36 hours = 81.8 (56.5–92.1) μg hour mL^?1; absorption half-life = 0.38 (0.25–1.11) hours; elimination half-life = 6.90 (6.21–7.40) hours; time over 2.8 μg mL^?1 (the presumed minimal effective concentration) = 11.11 (6.97–14.47) hours; maximal plasma concentration (C_max) = 7.15 (4.6–7.9) μg mL^?1; time for C_max to occur = 1.5 (1.0–4.0) hours. Assuming an 8-hour dosing interval, predicted minimal, average, and maximal steady state plasma concentrations were 6.5 (4.8–8.1), 8.8 (7.3–10.9), and 13.0 (8.8–15.2) μg mL^?1. The corresponding values assuming a 12-hour interval were 3.8 (2.4–4.8), 6.8 (4.9–7.9), and 10.1 (6.6–11.6) μg mL^?1.Conclusions and clinical relevancePregabalin 4 mg kg^?1 PO produces plasma concentrations within the extrapolated therapeutic range from humans for sufficient time to suggest that a twice daily dosing regime would be adequate. Further study of the drug's safety and efficacy for the treatment of neuropathic pain and seizures in dogs is warranted.