Pharmacokinetics and clinical efficacy of cyclosporine treatment of dogs with steroid-refractory inflammatory bowel disease

The usual treatment of dogs with inflammatory bowel disease (IBD) consists of administration of immunosuppressive doses of steroids. However, some dogs are refractory to steroid treatment and pose a significant challenge to the veterinarian. Because cyclosporine A (cyA) has been shown to be effective in steroid-resistant IBD in humans, the purpose of this study was to investigate the pharmacokinetics and clinical efficacy of PO cyA treatment in dogs with steroid-refractory IBD (n = 14). All dogs were treated with cyA 5 mg/kg PO q24h for a period of 10 weeks. A clinical activity score was assigned to assess severity of clinical signs before and after treatment. The total number of infiltrating lymphocytes and T cells in duodenal biopsies were assessed before and after treatment in 9 dogs. In addition, serum concentration of cyA was measured in 8 dogs over a 24-hour period. Pharmacokinetic profiles in dogs with IBD were similar to those of healthy dogs. Improvement of clinical signs was observed in 12 of 14 dogs with IBD. Median clinical activity score after treatment with cyA was significantly reduced from a median score of 9 to a median score of 5 (P = 0.001). T cell numbers in duodenal biopsies were significantly decreased after treatment from a median +/- 95% range in the villous region of 28 (19-30) cells/10,000 microm2 before versus 7 (0-10)/10,000 microm2 after treatment, P = 0.01; and from a median +/- 95% range number in the crypt region of 15 (6-23) cells/10,000 microm2 before versus 4 (0-9)/10,000 microm2 after treatment, P = 0.02, implying T cell lysis as a possible mechanism of action. In conclusion, based on this small study, cyA appears to be an effective alternative drug in dogs with IBD that are refractory to immunosuppressive doses of steroids.     

Tolerability and efficacy of benazepril in cats with chronic kidney disease

The objective of the study was to test the effect of the angiotensin-converting enzyme inhibitor (ACEI) benazepril in cats with chronic kidney disease (CKD). A total of 192 cats with CKD with an initial plasma creatinine concentration > or = 2 mg/dL (> or = 177 micromol/L) and urine specific gravity < or = 1.025 were recruited into a double-blind, parallel-group, prospective, randomized clinical trial. Cats received daily (q24h) PO placebo (n = 96) or benazepril x HCl at a dosage of 0.5-1.0 mg/kg (n = 96) for up to 1,119 days. Most cats were fed exclusively a diet containing low amounts of phosphate, protein, and sodium. Benazepril produced a significant reduction in proteinuria, assessed by the urine protein-to-creatinine ratio (UPC, P = .005). This effect of benazepril was present in all subgroups tested, including cats with UPC <0.2, although the effect was largest in cats with higher UPCs. Plasma protein was maintained at higher concentrations with benazepril as compared with placebo during treatment in cats with initial UPC <1 (P = .038 versus P = .079 for all cats). There was no difference in renal survival time between the 2 groups when all 192 cats were compared. Mean +/- SD renal survival times were 637 +/- 480 days with benazepril and 520 +/- 323 days with placebo (P = .47). Mean +/- SD renal survival times in the 13 cats with initial UPC > or = 1 were 402 +/- 202 days with benazepril and 149 +/- 90 days with placebo (P = .27). Cats with initial UPC > or = 1 treated with benazepril had better appetite (P = .017) as compared with those treated with placebo. Benazepril was well tolerated. In conclusion, benazepril decreased proteinuria in cats with CKD.     

Efficacy of enalapril for prevention of congestive heart failure in dogs with myxomatous valve disease and asymptomatic mitral regurgitation

We evaluated the long-term effect of early angiotensin-converting enzyme (ACE) inhibition (enalapril maleate) as monotherapy to postpone or prevent congestive heart failure (CHF) in asymptomatic dogs with mitral regurgitation (MR) attributable to myxomatous valvular disease (MVD) in a prospective, randomized, double-blinded, placebo-controlled multicenter trial involving 14 centers in Scandinavia. Two hundred twenty-nine Cavalier King Charles (CKC) Spaniels with MR attributable to MVD but no signs of CHF were randomly allocated to treatment with enalapril 0.25-0.5 mg daily (n = 116) or to placebo groups (n = 113). Each dog was evaluated by physical examination, electrocardiography, and thoracic radiography at entry and every 12 months (+/-30 days). The number of dogs developing heart failure was similar in the treatment and placebo groups (n = 50 [43%] and n = 48 [42%], respectively; P = .99). The estimated means, adjusted for censored observations, for the period from initiation of therapy to heart failure were 1,150 +/- 50 days for dogs in the treatment group and 1,130 +/- 50 days for dogs in the placebo group (P = .85). When absence or presence of cardiomegaly at the entrance of the trial was considered, there were still no differences between the treatment and placebo groups (P = .98 and .51, respectively). Multivariate analysis showed that enalapril had no significant effect on the time from initiation of therapy to heart failure (P = .86). Long-term treatment with enalapril in asymptomatic dogs with MVD and MR did not delay the onset of heart failure regardless of whether or not cardiomegaly was present at initiation of the study.     

Glomerular filtration rate in dogs with leishmaniasis and chronic kidney disease

BACKGROUND: Glomerular filtration rate (GFR) measurement is an indicator of kidney function. However, its usefulness in dogs at early stages of spontaneous chronic kidney disease (CKD) of glomerular origin, where routine laboratory techniques are not sufficiently sensitive, remains unproved. HYPOTHESIS: That GFR is reduced in proteinuric nonazotemic or mildly azotemic dogs with CKD secondary to leishmaniasis. ANIMALS: Twenty-six dogs with CKD secondary to leishmaniasis and 10 healthy dogs (control group). METHODS: CBC, serum biochemistry, and urinalysis (microalbuminuria and urine protein/creatinine ratio [UPC]) were performed in all dogs. GFR was calculated by measuring exogenous creatinine clearance. Based on degree of proteinuria and serum creatinine concentration (SCr), dogs were classified as group A (control; n = 10): UPC < 0.2, SCr < 1.4 mg/dL; group B (n = 8): UPC, 0.2-0.5, SCr < 1.4 mg/dL; group C (n = 10): UPC > 0.5, SCr < 1.4 mg/dL; group D (n = 5): SCr, 1.4-2 mg/dL; group E (n = 3): SCr > 2 mg/dL. Results: GFR (mL/kg/min) was 3.9 +/- 0.29, 4.4 +/- 0.74, 4.5 +/- 1.44, 2.8 +/- 0.97, and 1.5 +/- 0.43 for groups A, B, C, D, and E, respectively. Eleven dogs (1 from group B, 3 from group C, 4 from group D, and all 3 dogs from group E) had an abnormally low GFR. Four dogs from group B and 5 dogs from group C had a GFR above the upper reference range (>4.5 mL/min/kg). CONCLUSION AND CLINICAL RELEVANCE: Some proteinuric nonazotemic or mildly azotemic dogs with leishmaniasis have low GFR, but glomerular hyperfiltration occurs in other dogs.     

Effects of long-term administration of enalapril on clinical indicators of renal function in dogs with compensated mitral regurgitation

OBJECTIVE: To determine the effect of long-term administration of enalapril on renal function in dogs with severe, compensated mitral regurgitation. DESIGN: Randomized controlled trial. ANIMALS: 139 dogs with mitral regurgitation but without overt signs of heart failure. PROCEDURE: Dogs were randomly assigned to be treated with enalapril (0.5 mg/kg [0.23 mg/lb], PO, q 24 h) or placebo, and serum creatinine and urea nitrogen concentrations were measured at regular intervals for up to 26 months. RESULTS: Adequate information on renal function was obtained from 132 dogs; follow-up time ranged from 0.5 to 26 months (median, 12 months). Mean serum creatinine and urea nitrogen concentrations were not significantly different between dogs receiving enalapril and dogs receiving the placebo at any time, nor were concentrations significantly different from baseline concentrations. Proportions of dogs that developed azotemia or that had a +/- 35% increase in serum creatinine or urea nitrogen concentration were also not significantly different between groups. Conclusions: And Clinical Relevance: Results suggest that administration of enalapril for up to 2 years did not have any demonstrable adverse effects on renal function in dogs with severe, compensated mitral regurgitation.     

Effect of orally administered hydrocortisone on intraocular pressure in nonglaucomatous dogs

OBJECTIVE: To determine the effect of oral hydrocortisone on intraocular pressure (IOP) in ocular normotensive dogs. ANIMALS STUDIED: Seventeen ocular normotensive dogs. Procedures Dogs were randomly assigned to treatment (n = 9) and control (n = 8) groups. Dogs in the treatment group received hydrocortisone, 3.3 mg/kg PO every 8 h, and dogs in the control group received gelatin capsule placebo PO every 8 h for 5 weeks. Applanation tonometry was performed on both eyes of all dogs prior to treatment and then once weekly for 5 weeks during hydrocortisone treatment. RESULTS: No significant effect of treatment was noted for right (P = 0.1013) or left (P = 0.1157) eyes during the treatment period, nor was there significant interaction of treatment by week for the right (P = 0.9456) or left (P = 0.3577) eyes. A significant rise in IOP over the treatment period was noted in both right (P < 0.0001) and left (P = 0.0006) eyes of both groups, but was unrelated to treatment. CONCLUSION: Orally administered hydrocortisone does not significantly increase IOP in nonglaucomatous dogs when administered over a 5-week period.     

Effect of early enteral nutrition on intestinal permeability, intestinal protein loss, and outcome in dogs with severe parvoviral enteritis

A randomized, controlled clinical trial investigated the effect of early enteral nutrition (EN) on intestinal permeability, intestinal protein loss, and outcome in parvoviral enteritis. Dogs were randomized into 2 groups: 15 dogs received no food until vomiting had ceased for 12 hours (mean 50 hours after admission; NPO group), and 15 dogs received early EN by nasoesophageal tube from 12 hours after admission (EEN group). All other treatments were identical. Intestinal permeability was assessed by 6-hour urinary lactulose (L) and rhamnose (R) recoveries (%L, %R) and L/R recovery ratios. Intestinal protein loss was quantified by fecal alpha1-proteinase inhibitor concentrations (alpha1-PI). Median time to normalization of demeanor, appetite, vomiting, and diarrhea was 1 day shorter for the EEN group for each variable. Body weight increased insignificantly from admission in the NPO group (day 3: 2.5 +/- 2.8%; day 6: 4.3 +/- 2.3%; mean +/- SE), whereas the EEN group exhibited significant weight gain (day 3: 8.1 +/- 2.7%; day 6: 9.7 +/- 2.1%). Mean urinary %L was increased, %R reduced, and L/R recovery ratios increased compared to reference values throughout the study for both groups. Percent lactulose recovery decreased in the EEN group (admission: 22.6 +/- 8.0%; day 6: 17.9 +/- 2.3%) and increased in the NPO group (admission: 11.0 +/- 2.6%; day 6: 22.5 +/- 4.6%, P = .035). Fecal alpha1-PI was above reference values in both groups and declined progressively. No significant differences occurred for %R, L/R ratios, or alpha1-PI between groups. Thirteen NPO dogs and all EEN dogs survived (P = .48). The EEN group showed earlier clinical improvement and significant weight gain. The significantly decreased %L in the EEN versus NPO group might reflect improved gut barrier function, which could limit bacterial or endotoxin translocation.     

Efficacy of omeprazole for the prevention of exercise-induced gastritis in racing Alaskan sled dogs

Exercise-induced gastritis and gastric ulcers are common in humans and horses, and recently have been described in racing sled dogs. The cause of exercise-induced gastric disease is not completely understood in any species, but pharmacologic suppression of acid secretion is an effective treatment in humans and horses. Thus, we tested the hypothesis that omeprazole, a proton-pump inhibitor shown to reduce gastric acid secretion in dogs, would reduce the severity of exercise-induced gastric disease. Three teams of 16 dogs each competing in the 2002 Iditarod Sled Dog Race were recruited for participation. Within each team, dogs were randomly assigned to either treatment (20 mg omeprazole PO q24h) or placebo. Treatments were administered until either completion of the race or withdrawal of an individual dog from competition. Gastric endoscopy was performed in all dogs 24 hours after completion or withdrawal, and the gastric mucosa was scored by using a subjective severity score (0 = normal, 3 = numerous bleeding ulcers). Treatment with omeprazole significantly reduced mean gastricseverity score compared to placebo (omeprazole: 0.65 +/- 0.17, placebo: 1.09 +/- 0.18; P = .028), but also was associated with increased frequency of diarrhea during the race (omeprazole 54%, placebo 21%; P = .017). Examination of our data suggests that omeprazole may be an effective treatment for exercise-induced gastric disease in racing sled dogs. However, further investigation regarding the cause and clinical relevance of diarrhea associated with omeprazole treatment must be conducted before omeprazole can be recommended for routine prophylactic treatment in these athletes.     

Controlled Clinical Evaluation of Enalapril in Dogs With Heart Failure: Results of the Cooperative Veterinary Enalapril Study Group The COVE Study Group

The clinical efficacy and safety of enalapril were evaluated in dogs with moderate or severe heart failure. This study was conducted at 19 centers and included 211 clientowned dogs with heart failure caused by mitral regurgitation (MR) due to acquired valvular disease or dilated cardiomyopathy (DCM). Dogs of various breeds, ages, and weights were included in the study. Replicates of 2 dogs each were formed, using separate allocation schedules for dogs with MR or DCM. One dog within each replicate received placebo tablets (vehicle tablets without enalapril) PO sid or bid, and the other dog received enalapril tablets at approximately 0.5 mg/kg sid or bid, based on individual need. In addition to the experimental drug, all dogs, except 1 in the placebo group, received furosemide; 73.3% of the dogs in the placebo group and 78.3% of those in the enala pril group received digoxin. Doses of enalapril or placebo were administered for approximately 28 days. In the placebo group, 68.6% of the dogs completed the study compared with 84.9% in the enalapril group; the difference between groups was significant ( P = .01). Significantly ( P = .01) more dogs in the placebo group compared with the enalapril group died or were removed from the study because of progression of heart failure. On day 28, all 14 clinical variables measured improved significantly ( P = .01) in the enalapril group compared with the placebo group. Five dogs (3 from the placebo group and 2 from the enalapril group) had to be removed from the study as a result of azotemia.     

Effect of pimobendan on case fatality rate in Doberman Pinschers with congestive heart failure caused by dilated cardiomyopathy

BACKGROUND: Despite traditional therapy of a diuretic, angiotensin converting enzyme inhibitor, digoxin, or a combination of these drugs, survival of dogs with dilated cardiomyopathy (DCM) is low. Pimobendan, an inodilator, has both inotropic and balanced peripheral vasodilatory properties. HYPOTHESIS: Pimobendan when added to conventional therapy will improve morbidity and reduce case fatality rate in Doberman Pinschers with congestive heart failure (CHF) caused by DCM. ANIMALS: Sixteen Doberman Pinschers in CHF caused by DCM. METHODS: A prospective randomized, double-blind, placebo-controlled study with treatment failure as the primary and quality of life (QoL) indices as secondary outcome variables. Therapy consisted of furosemide (per os [PO] as required) and benazepril hydrochloride (0.5 mg/kg PO q12h) and dogs were randomized in pairs and by sex to receive pimobendan (0.25 mg/kg PO q12h) or placebo (1 tablet PO q12h). RESULTS: Pimobendan-treated dogs had a significant improvement in time to treatment failure (pimobendan median, 130.5 days; placebo median, 14 days; P= .002; risk ratio = 0.35, P= .003, lower 5% confidence limit = 0.13, upper 95% confidence limit = 0.71). Number and rate of dogs reaching treatment failure in the placebo group precluded the analysis of QoL. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan should be used as a first-line therapeutic in Doberman Pinschers for the treatment of CHF caused by DCM.     

Efficacy of mepyramine maleate treatment in dogs with angioedema

Twenty-seven dogs with angioedema, were enrolled in this clinical study. The cases were randomly assigned to the treatment group (n=15) and untreated placebo control group (n=12). It was concluded that mepyramine maleate has the potential to be helpful for dogs with angioedema.     

Effects of carvedilol treatment in dogs with chronic mitral valvular disease

BACKGROUND: Stimulation of the sympathetic nervous system occurs during the development of heart failure in dogs with chronic mitral valvular disease (CMVD). HYPOTHESIS: The use of beta-blockers to modulate the activation of the sympathetic nervous system would be useful in dogs with CMVD. ANIMALS: Group A included 13 dogs who received the conventional treatment (digoxin, benazepril, a reduced sodium diet, and codeine, and a diuretic when indicated), and group B included 12 dogs who received the protocol above plus carvedilol (0.3 mg/kg q12h). METHODS: Blinded, placebo, controlled study. RESULTS: The main echodopplercardiographic variables, heart rate, biochemical data, functional classification (FC) (New York Heart Association) and quality of life score (functional evaluation of cardiac health questionnaire) were assessed at baseline (TO) and after 3 months (T1). Only group B showed improvement in score of quality of life (13.8 +/- 8.8 versus 6.0 +/- 6.3; P < .001), in FC (2.4 - 0.9 versus 1.8 +/- 0.7; P = .032) and a reduction in systolic blood pressure (151.2 +/- 18.3 versus 124.5 +/- 23.4; P = .021). Two deaths from group A and 1 from B were related to CMVD. CONCLUSION: The studied dose of carvedilol in this group did not improve the sympathetic activation and echocardiographic variables over 3 months of chronic oral treatment. However, the results suggested a beneficial effect on the quality of life score, functional classification, and a reduction on systolic blood pressure.     

Effects of meloxicam on severity of lameness and other clinical signs of osteoarthritis in dogs

OBJECTIVE: To evaluate effects of meloxicam on severity of lameness and other clinical signs in dogs with osteoarthritis (OA). DESIGN: Randomized, controlled, multicenter clinical trial. ANIMALS: 217 client-owned dogs with clinical and radiographic signs of OA. PROCEDURE: Dogs were randomly assigned to be treated with meloxicam (n = 105; 0.2 mg/kg [0.09 mg/lb], SC, once on day 1, then 0.1 mg/kg [0.045 mg/lb], PO, q 24 h, for 13 days) or a placebo (n = 112). A general clinical score was assigned by investigators on days 1 (ie, prior to initiation of treatment), 8, and 15 on the basis of severity of lameness, extent of weight bearing, and severity of signs during palpation of the affected joint. Owners and investigators provided overall evaluations on days 8 and 15. RESULTS: Dogs treated with meloxicam had significantly greater improvements in general clinical scores, compared with baseline scores, on days 8 and 15 than did dogs treated with placebo. On days 8 and 15, percentages of dogs treated with meloxicam in which owners and investigators considered treatment to be successful were significantly higher than percentages of control dogs in which treatment was considered to be successful. No abnormalities in hematologic and serum biochemical test results were detected. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that compared with administration of a placebo, administration of meloxicam for 14 days significantly improved the clinical condition of dogs with OA without causing adverse effects.     

Effects of renal impairment on the disposition of orally administered enalapril, benazepril, and their active metabolites

The pharmacokinetics of benazepril, enalapril, and their active metabolites (benazeprilat and enalaprilat) were compared after a single administration of each product by the oral route at the recommended dosage (0.5 mg/kg for both drugs) in the dog before and after moderate experimental renal impairment. Ten dogs were randomly assigned to 2 groups of 5 animals in a 2-period crossover design for angiotensin-converting enzyme inhibitor administration. Renal failure was surgically induced by right nephrectomy and electrocoagulation of the remaining kidney. Renal mass reduction induced a significant decrease (P < .001) in glomerular filtration rate (GFR) (1.7 +/- 0.3 versus 3.3 +/- 0.7 mL/kg/minute). No significant differences before and after surgery were observed for enalapril and benazepril kinetics. The area under the curve (AUC) for enalaprilat increased after surgery from 23.6 +/- 14.7 to 42.4 +/- 20.9 micrograms.minute/mL (P < .01). Mean peak plasma concentration (Cmax) was increased in the impaired dogs (59.1 +/- 23.3 versus 43.9 +/- 32.9 ng/mL), but this variation was not significant (P > .05). Renal failure had no significant effect on AUC for benazeprilat (13.8 +/- 9.8 versus 14.9 +/- 5.0 micrograms.minute/mL) (P > .05), but Cmax decreased significantly (from 55.0 +/- 26.4 to 31.9 +/- 17.7 ng/mL) (P < .05). Multiple regression analysis showed that both GFR and AUC for enalapril were highly significant variables that explained the variation in AUC for enalaprilat (R2 = .86, P < .001) but not for benazeprilat (R2 = .12, P > .05). The results of this study indicate that exposure to enalaprilat, but not to benazeprilat, is increased in dogs with subclinical renal impairment.     

Cardiopulmonary effects of medetomidine, oxymorphone, or butorphanol in selegiline-treated dogs

OBJECTIVES: To determine if chronic selegiline HCl administration affects the cardiopulmonary response to medetomidine, oxymorphone, or butorphanol in dogs. STUDY DESIGN: Prospective randomized experimental study. ANIMALS: Twenty-eight adult, random source, hound dogs weighing 21-33 kg. METHODS: Dogs were assigned to the following treatment groups: selegiline + medetomidine (MED; n = 6); placebo + MED (n = 6), selegiline + oxymorphone (OXY; n = 6); placebo + OXY (n = 6); selegiline + butorphanol (BUT; n = 7) or placebo + BUT (n = 6). Nine dogs were treated with two of the three pre-medicants. Dogs were treated with selegiline (1 mg kg(-1) PO, q 24 hours) or placebo for at least 44 days prior to pre-medicant administration. On the day of the experiment, arterial blood for blood gas analysis, blood pressure measurements, ECG, cardiac ultrasound (mM-mode, 2-D, and continuous wave Doppler), and behavioral observations were obtained by blinded observers. An IV injection of MED (750 micro g m(-2)), OXY (0.1 mg kg(-1)) or BUT (0.4 mg kg(-1)) was given. Cardiopulmonary and behavioral data were collected at 1, 2, 5, 15, 30, and 60 minutes after injection. RESULTS: Selegiline did not modify responses to any of the pre-medicant drugs. Medetomidine caused a significant decrease in heart rate (HR), cardiac output (CO), and fractional shortening (FS). Mean arterial pressure (MAP), systemic vascular resistance (SVR), and central venous pressure (CVP) were increased. Level of consciousness and resistance to restraint were both decreased. Oxymorphone did not affect MAP, CO, CVP, or SVR, but RR and PaCO(2) were increased. Level of consciousness and resistance to restraint were decreased. BUT decreased heart rate at 1 and 5 minutes. All other cardiovascular parameters were unchanged. BUT administration was associated with decreased arterial pH and increased PaCO(2). BUT decreased level of consciousness and resistance to restraint. CONCLUSIONS AND CLINICAL RELEVANCE: Although pre-medicants themselves altered cardiopulmonary and behavioral function, selegiline did not affect the response to medetomidine, oxymorphone, or butorphanol in this group of normal dogs.     

Comparison of platelet count recovery with use of vincristine and prednisone or prednisone alone for treatment for severe immune-mediated thrombocytopenia in dogs

OBJECTIVE: To evaluate the effect of prednisone alone, compared with a combination of prednisone and vincristine, on platelet counts in bleeding dogs with severe primary immune-mediated thrombocytopenia (IMT). DESIGN: Prospective case study. ANIMALS: 24 dogs with severe primary IMT PROCEDURE: All dogs received immunosuppressive doses of prednisone (1.5 to 2 mg/kg [0.7 to 0.9 mg/lb] of body weight, PO, q 12 h). In addition, 12 dogs received a single dose of vincristine (0.02 mg/kg [0.01 mg/lb], IV). Platelet count, transfusion requirement, and outcome were monitored. A response was defined as an increase in platelet count to > or = 40,000/microl. Dogs in the prednisone group that failed to respond received 1 dose of vincristine on day 7. RESULTS: Dogs that received prednisone and vincristine had a significantly faster increase in platelet count to > or = 40,000 platelets/microl than dogs that received prednisone alone (mean +/- SD, 4.9 +/- 1.1 vs 6.8 +/- 4.5 days, respectively). A similarly rapid response was observed in dogs that received vincristine on day 7 after treatment with prednisone alone failed. Furthermore, duration of hospitalization was reduced in the vincristine group, compared with the prednisone group (5.4 +/- 0.3 vs 7.3 +/- 0.5 days, respectively). No adverse effects attributable to vincristine were observed in any dog. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of combined vincristine and prednisone is associated with more rapid increase in platelet numbers and shortened duration of hospitalization in dogs with IMT, compared with use of prednisone alone. Early use of vincristine seems warranted in dogs with severe primary IMT.     

Serum concentrations of thyroxine and 3,5,3'-triiodothyronine before and after intravenous or intramuscular thyrotropin administration in dogs

Response to thyrotropin (TSH) was evaluated in 2 groups of mixed-breed dogs. Thyrotropin (5 IU) was administered IV to dogs in group 1 (n = 15) and IM to dogs in group 2 (n = 15). Venous blood samples were collected immediately before administration of TSH and at 2-hour intervals for 12 hours thereafter. In group 1, the maximum mean concentration (+/- SD) of thyroxine (T4; 7.76 +/- 2.60 micrograms/dl) and 3,5,3'-triiodothyroxine (T3; 1.56 +/- 0.51 ng/ml) was attained at postinjection hours (PIH) 8 and 6, respectively. However, the mean concentration of T4 at PIH 6 (7.21 +/- 2.39 micrograms/dl) was not different (P greater than 0.05) from the mean concentration at PIH 8. The maximum mean concentration of T4 (10.10 +/- 3.50 micrograms/dl) and T3 (2.22 +/- 1.24 ng/ml) in group 2 was attained at PIH 12 and 10, respectively. Because dogs given TSH by the IM route manifested pain during injection, had variable serum concentrations of T3 after TSH administration, and may require 5 IU to achieve maximal increases in serum T4 concentrations, IV administration of TSH is recommended. The optimal sampling time to observe maximal increases in T3 and T4 after IV administration of TSH was 6 hours. Repeat IV administration of TSH may cause anaphylaxis and, therefore, is not recommended.     

Effect of S-adenosylmethionine tablets on the reduction of age-related mental decline in dogs: a double-blinded, placebo-controlled trial

Oral S-adenosylmethionine (SAMe) tosylate supplementation (Novifit tablets, Virbac) was evaluated as a dietary aid for the management of age-related mental impairment in dogs. Thirty-six dogs older than 8 years that had displayed signs of cognitive dysfunction for at least 1 month were selected for the study. The dogs were administered 18 mg/kg SAMe tosylate (n=17) or identical placebo tablets (n=19) for 2 months. Concurrent behavioral treatment was forbidden. A 14-item standardized questionnaire evaluated behavior and locomotion difficulties. Compared with the placebo group, SAMe-treated dogs showed greater improvement in activity (41.7% versus 2.6% after 4 weeks, P<.0003; 57.1% versus 9.0% after 8 weeks, P<.003) and awareness (33.3% versus 17.9% after 4 weeks, P<.05; 59.5% versus 21.4% after 8 weeks, P<.01). The aggregate mental impairment score was reduced by more than 50% in 41.2% and 15.8% of dogs treated with SAMe and placebo, respectively, at week 8. SAMe tosylate tablets proved safe and effective in improving signs of age-related mental decline in dogs.     

Clinical evaluation of pimecrolimus eye drops for treatment of canine keratoconjunctivitis sicca: a comparison with cyclosporine A

The aim of this study was to evaluate the efficacy of pimecrolimus oil-based eye drops in alleviating the clinical signs of keratoconjunctivitis sicca (KCS) in dogs and to compare the efficacy with that of cyclosporine A (CsA) ointment. An open-label, multicenter study enrolling 44 dogs previously untreated with CsA was conducted. Dogs were randomly assigned to a treatment group and medicated twice daily for 8 weeks. After that time the mean increase (+/-SEM) in the Schirmer tear test was 9.2+/-1.6 mm/min in the pimecrolimus group and 5.8+/-1.1 mm/min in the CsA group (P=0.085). The improvement in clinical signs of inflammation in eyes treated with pimecrolimus was significantly greater than in eyes treated with CsA (P=0.02). The results show that 1% pimecrolimus oily eye drops are as safe as and more effective than CsA ointment in controlling KCS in dogs.     

Investigation of diagnostic importance of platelet closure times measured by Platelet Function Analyzer--PFA 100 in dogs with endotoxemia

This study was performed to evaluate the diagnostic importance of the platelet closure times measured by the Platelet Function Analyzer (PFA-100) in dogs with endotoxemia. E. coli endotoxin was given intravenously once, at the dose of 0.02 mg/kg or 1 mg/kg in groups I (n=9) and II (n=8), respectively. Normal saline (0.1 ml/kg) was injected in group III (n=8).The dogs were monitored for 48 h, and venous blood samples were collected prior to (baseline) and at intervals of 0.5, 1, 2, 4, 6, 8, 12, 24 and 48 h subsequent to the treatments. The white blood cell (WBC), platelet counts, and hematocrit (Hct) values were recorded. Platelet closure times were determined, using collagen/epinephrine (CEPI) and collagen/adenosine diphosphate (CADP) cartridges. Within 0.5 h after the endotoxin application baseline WBC and platelet counts (mean +/-SD) decreased significantly (p<0.001) to 2000 +/- 500 and 1850 +/- 200 cells/microl or 69.000 +/- 12.500 and 27.000 +/- 6.400 cells/microl in groups I and II, respectively. Platelet counts remained low during the first 1-48 h, but the WBC count was high at the 8th-48th h, in groups I and II, compared with baselines (p<0.001). After the application of the endotoxin, Hct values increased from baseline values of 37 +/- 3 or 39 +/- 2% to 48 +/- 2 or 51 +/- 3%, within 1 h (p<0.001), in groups I and II, respectively. Hct values in group II were notably higher (p<0.001) than those of group I, during the 2nd-48th h. Hematological parameters and closure times did not differ significantly throughout the study in group III. Baseline closure time ranged from 79 +/- 5 seconds (s) to 86 +/- 5 s for CADP and 144 +/- 13 s to 159 +/- 14 s for CEPI in all dogs (n=25). At 0.5 h after the endotoxin, the closure times of CADP as well as CEPI declined to 62 +/- 6 s and 76 +/- 8 s in group I (p<0.001) and 57 +/- 5 s and 75 +/- 6 s in group II (p<0.001). Afterwards, closure time prolonged to the levels of 280 +/- 8 s (CADP) and 294 +/- 5 s (CEPI) by 48 h (p<0.001) in group II, but returned to the baseline limit in group I. In conclusion, our results show that the shortened closure times may serve as a very early diagnostic sign of endotoxemia, prolonged closure times however may be used as an index for the severity of endotoxemia.