Renal Allograft Survival in Outbred Mongrel Dogs Using Rabbit Anti-Dog Thymocyte Serum in Combination With Immunosuppressive Drug Therapy With or Without Donor Bone Marrow

Therapeutic renal transplantation in dogs is currently being investigated as a treatment for end-stage renal disease. This pilot study examines the effect of donor bone marrow (DBM) infusion and antithymocyte serum (ATS) in combination with immunosuppressive drug therapy in prolonging renal allograft survival in dogs. Seven normal outbred mongrel dogs received an unmatched renal allograft. All dogs received rabbit anti-dog thymocyte serum (RADTS), prednisone (Pr), cyclosporine-A (CsA) and azathioprine (Aza). In addition, three dogs (group 1 test) received DBM and four dogs (group 2 control) did not receive DBM. Serum CsA levels were measured throughout the study. Immunosuppressive therapy was gradually reduced with Pr, CsA, and Aza withdrawn at 200,450, and 680 days, respectively. Allograft rejection was treated with prednisolone sodium succinate. One dog in group 1 and one in group 2 died as a result of infectious canine rhinotracheitis and rejection early in the study. Renal allograft torsion occurred in one group 1 dog. The remaining four dogs survived the 2 years of the study. The dogs in group 2 (three dogs) all rejected the renal allograft after total drug withdrawal, the surviving dog in group 1 did not. This study demonstrates that RADTS, Pr, CsA, and Aza in combination can prolong renal allograft survival in mongrel dogs, whereas DBM may enhance the unresponsive state.     

An evaluation of combined immunosuppression with MNA 715 and microemulsified cyclosporine on renal allograft rejection in mismatched mongrel dogs

OBJECTIVE: To evaluate a combination of MNA 715 and microemulsifed cyclosporine for the prevention of renal allograft rejection in mismatched mongrel dogs. STUDY DESIGN: Randomized, experimental study. ANIMALS: Fourteen female mismatched mongrel dogs. METHODS: Heterotopic renal transplantation and bilateral nephrectomy were performed in each dog. Dogs were randomly assigned to receive either MNA 715 and cyclosporine (n = 8) or cyclosporine alone (n = 6). Dogs were killed at 100 days after transplantation or when plasma creatinine exceeded 7 mg/dL. RESULTS: In the cyclosporine and MNA 715 group: 4 dogs survived to 100 days with normal plasma creatinine concentrations; 2 dogs with intestinal intussusceptions were killed at 5 and 8 days, 1 dog with a wound infection and sepsis was killed at 14 days, and 1 dog with a serum creatinine concentration >7 mg/dL was killed at 51 days postoperatively. In the cyclosporine-alone group: 3 dogs with acute rejection were killed at 6 to 9 days and 3 dogs survived to 100 days. In dogs treated with cyclosporine and MNA 715, survival to histologically confirmed acute rejection was significantly longer (P =.044) and the degree of mononuclear cell infiltration was significantly reduced (P =.040), compared with dogs treated with cyclosporine alone. CONCLUSIONS: MNA 715 combined with cyclosporine prolonged allograft survival and reduced the severity of histologic rejection in a clinically relevant renal transplant model. CLINICAL RELEVANCE: An immunosuppressive regimen consisting of MNA715 and microemulsified cyclosporine may be effective in preventing allograft rejection in canine renal transplant patients.     

Prednisone treatment alters the serum amylase and lipase activities in normal dogs without causing pancreatitis.

In order to test the hypothesis that treatment with glucocorticoids causes pancreatitis in dogs, 18 mongrel dogs were divided into three groups of six individuals, each group receiving prednisone at different doses orally or intramuscularly for two weeks. Two groups consisting of six dogs each served as controls. Treatment for two weeks with oral prednisone at 1.2 mg/kg body weight or at 4 mg/kg body weight daily decreased the serum amylase activities, but increased the serum lipase activities. Postmortem examinations revealed microscopic evidence of mild pancreatitis in only one dog given prednisone, that clinically appeared normal. It was concluded that daily doses of 4 mg prednisone/kg body weight or less given orally or intramuscularly for two weeks do not cause pancreatitis in dogs.     

Renal allograft histopathology in dog leukocyte antigen mismatched dogs after renal transplantation

OBJECTIVE: To evaluate allograft histopathology in dog leukocyte antigen (DLA)-mismatched dogs undergoing renal transplantation, with transient immunosuppression. STUDY DESIGN: Prospective study. ANIMALS: Ten healthy adult mongrel dogs. METHODS: Reciprocal renal transplantation and bilateral nephrectomy were performed. Immune conditioning consisted of nonmyeloablative (200 cGy), total body irradiation (TBI), bone marrow transplantation (BMT; 7 dogs), cyclosporine (CSA; 15 mg/kg every 12 hours), mycophenolate mofetil (MMF; 10 mg/kg every 12 hours) and intermittent prednisone (1 mg/kg every 12-24 hours). Biopsies were collected at transplantation, during full immunosuppression (44-90 days), and once medications were reduced or discontinued (228-580 days). Biopsies were evaluated for interstitial, tubular, vascular, and glomerular lesions. Blood urea nitrogen, creatinine, serum CSA concentrations, and clinical score were determined at each biopsy. RESULTS: Seven dogs survived >200 days (mean, 380 days). Transient CSA toxicity was suspected in 6 dogs. Lymphocytic, plasmacytic interstitial inflammation, and tubulitis progressed when immunosuppressive medications were decreased. All 7 dogs had histologic lesions consistent with some degree of allograft rejection at study end. CONCLUSION: Nonmyeloablative TBI, BMT, and short-term immunosuppression with CSA, MMF, and prednisone allowed renal allograft function and dog survival for >200 days. It appears unlikely that total drug withdrawal will be possible in unrelated DLA-mismatched dogs using this protocol. CLINICAL RELEVANCE: Transient immunosuppression with MMF, CSA, and prednisone along with BMT and nonmyeloablative TBI may make kidney transplantation a clinical reality for treatment of kidney failure in dogs. Initiating both MMF and CSA at lower dosages may potentially eliminate early renal allograft injury.     

Intravenous Human Immunoglobulin for the Treatment of Immune-Mediated Hemolytic Anemia in 13 Dogs

Intravenous immunoglobulin (IVGG) was administered to 13 of 37 dogs with immune-mediated hemolytic anemia. All dogs received concurrent prednisone therapy, 14 dogs also received cyclophosphamide; and a single dog each received cyclosporine, azathioprines, and danazol. Dogs that responded to prednisone therapy without IVGG generally did so within 7 days (mean ± standard deviation = 5.6 ± 2.9 days). Intravenous immunoglobulin was administered after 10.4 ± 6.6 days of prednisone therapy as an intravenous infusion of 0.5 g/kg (range 0.25 to 0.73 g/kg). Eleven dogs received a single treatment, 2 dogs each received 2 treatments. No relevant adverse effects were noted. Eleven dogs had an increase in PCV of at least 4% 2.2 ±1.5 days after IVGG infusion. In 10 of these dogs, the PCV continued to increase until the time of hospital discharge. One responder died 1 hour after the increase in PCV, 1 dog was euthanized within 24 hours of IVGG administration, and 1 dog had no response over a period of 13 days. Results of this study suggest that IVGG therapy may be of value in dogs with immune-mediated hemolytic anemia that do not respond within 7 days of appropriate corticosteroid therapy.     

Microemulsified cyclosporine-based immunosuppression for the prevention of acute renal allograft rejection in unrelated dogs: preliminary experimental study

OBJECTIVES: To determine whether the microemulsified formulation of cyclosporine (MCsA; Neoral; Novartis A.G.), combined with azathioprine (Imuran; Glaxo Wellcome), and prednisolone (Delta-Cortef; Upjohn), would be effective in preventing acute renal allograft rejection in unrelated mongrel dogs. To document any toxic effects associated with this drug combination. STUDY DESIGN: rospective, pilot study. ANIMALS: Four healthy, adult, mongrel, canine renal allograft recipients. METHODS: Heterotopic renal transplantation, with bilateral nephrectomy, was performed in 4 dogs. Allografts were harvested from 2 unrelated dogs that were to be euthanatized for reasons unrelated to this study. The dogs were treated for 100 days or until signs of illness or allograft rejection required euthanasia. Microemulsified cyclosporine (20 mg/kg/day), azathioprine (5 mg/kg every other day), and prednisolone (1 mg/kg/day) were administered for the prevention of acute rejection. Body weight, serum biochemistry profiles, complete blood counts, and trough whole-blood cyclosporine concentrations were measured throughout the study. Cyclosporine dose was adjusted to maintain a trough concentration of 400-500 ng/mL. Azathioprine dose was decreased if evidence of hepatotoxicity developed or if the total blood white cell count was <4,000 cells/micro L. The prednisolone was tapered by 0.25 mg/kg increments every 3 weeks and discontinued 14 days before the end of the study in the surviving dogs. Complications were recorded. A complete necropsy and histopathologic examination were performed in each recipient. RESULTS: Two of the 4 dogs survived the 100-day period. One dog was euthanatized at 8 days because of an intestinal intussusception. One dog was euthanatized at 64 days because of a severe upper respiratory infection. At the time of death, these 2 dogs had plasma creatinine concentrations of 1.5 and 2.6 mg/dL, respectively, with no histopathologic evidence of allograft rejection. All dogs had transient weight loss (range, 4.6%-17.7% of preoperative body weight) between days 7 and 14. Two dogs had evidence of hepatotoxicity. The 2 dogs surviving to 100 days had normal serum creatinine concentrations and no clinical signs of rejection. One of these dogs had evidence of a grade IIa acute/active rejection based on the modified BANFF 97 histopathologic classification. The second dog had no evidence of rejection or inflammation within the allograft. CONCLUSIONS: This preliminary experimental study shows that immunosuppression using MCsA, combined with azathioprine and prednisolone, may be effective in preventing acute renal allograft rejection in unrelated mongrel dogs for 100 days. Complications included ileocolic intussusception, upper respiratory infection, weight loss, and transient hepatotoxicity. CLINICAL RELEVANCE: Immunosuppression using MCsA, azathioprine, and prednisolone may be effective in preventing acute renal allograft rejection in unrelated, mongrel dogs. This triple drug protocol is cost-effective and was easy to administer. Further investigation is warranted to minimize toxic effects and to determine the efficacy of prophylactic renal biopsies to detect and treat subclinical acute/active rejection.     

Use of cyclosporine to treat granulomatous meningoencephalitis in three dogs

Use of cyclosporine to treat granulomatous meningoencephalitis in three dogs Three dogs with a presumptive diagnosis of granulomatous meningoencephalitis were treated with orally administered cyclosporine. In 2 dogs, cyclosporine administration replaced initial corticosteroid administration, and in 1 dog, cyclosporine was the only treatment used. One dog had the focal form of the disease in the brainstem, 1 dog had the focal form in the forebrain associated with a concurrent ocular form, and 1 dog had the disseminated form of disease. At 12-month follow-up, the 2 dogs with the focal form of the disease had no clinical signs. The dog with the disseminated form improved only partially, and euthanasia was performed 3 weeks after initial evaluation. Cyclosporine was considered effective at an initial dosage of 6 mg/kg (2.7 mg/lb) every 12 hours. Adverse effects associated with cyclosporine administration included transient lymphopenia, excessive shedding, and focal symmetric hair discoloration.     

Kidney graft survival in transfused and nontransfused sibling beagle dogs

In 6 pairs of sibling Beagle dogs, 1 kidney was exchanged between pairs, and contralateral nephrectomy was done. Previously, one dog of each pair was given blood transfusions from the donor of its allograft. All dogs were given azathioprine and prednisone postoperatively for immunosuppression. Four of 6 dogs given pretransplantation transfusions were healthy 1 year after surgical manipulation was done, and 2 died for reasons other than graft rejection. Of the 6 dogs that were not given pretransplantation transfusions, 3 were healthy after 1 years, but 2 were euthanatized because of graft rejection, and the last was euthanatized because of both graft rejection and intussusception. Other complications in these dogs were leukopenia (7 dogs), interdigital abscesses (2 dogs), urinary infection (3 dogs), and renal vein thrombosis (1 dog). Considering the lack of alternative methods for effective therapy for chronic renal failure in dogs, results of this study seem encouraging for selective use of renal transplantation, clinically. This study supports previous reports which indicated that pretransplantation transfusion enhanced graft survival in dogs.     

Cyclosporine treatment of anal furunculosis in 26 dogs

OBJECTIVES: To evaluate the effect of cyclosporine on anal furunculosis lesions in 26 dogs. METHODS: Lesions were graded as mild in 11 dogs, moderate in eight and severe in seven. Each dog was treated with approximately 4 mg/kg cyclosporine orally every 12 hours until the lesions resolved or showed no further improvement. Residual lesions were resected surgically. RESULTS: Eighteen dogs (69 per cent) experienced complete resolution, seven (27 per cent) improved but had residual lesions and one (4 per cent) showed no improvement. The mean duration of treatment until resolution or no further improvement was 8.8 weeks (range four to 24 weeks). Nine dogs (35 per cent) experienced recurrence. Six were from the group that had shown complete resolution and three were from the group that had surgery. Fifteen dogs (58 per cent) developed side effects to cyclosporine, although none required treatment to be discontinued. Mean duration of follow-up was 6.8 months (range one to 20 months). CLINICAL SIGNIFICANCE: Cyclosporine was effective at resolving or reducing anal furunculosis lesions in 25 of 26 dogs (96 per cent). However, residual or recurrent lesions remain a potential problem, and surgical resection or long-term cyclosporine treatment may be necessary in some dogs.     

Use of capecitabine to prevent acute renal allograft rejection in dog erythrocyte antigen-mismatched mongrel dogs

OBJECTIVE: To assess efficacy and toxicity of a capecitabine (CAP)-based regimen for preventing rejection of renal allografts in dog erythrocyte antigen (DEA)-mismatched mongrel dogs. STUDY DESIGN: Prospective, pilot study. ANIMALS: Eight healthy, unrelated, DEA mismatched, adult mongrel dogs. METHODS: All dogs received CAP, starting at 50 mg/m2 PO b.i.d. 4 days preoperatively, increasing to 200 mg/m2 PO b.i.d. by the day of surgery. All dogs received cyclosporine-A (CsA) and prednisolone starting 2 days preoperatively. Standard heterotopic renal transplantation with native nephrectomy was performed. After 90 days, surviving dogs were euthanatized and histopathologic examination was performed. RESULTS: Two of 8 dogs developed acute neurotoxicity leading to death or euthanasia within 5 days of surgery. For the 6 remaining dogs, there were no statistically significant changes in complete blood count or serum biochemical values. No opportunistic infections developed during the study period. Five of 6 dogs had no to minimal evidence of graft rejection. Two of 6 dogs developed superficial and pigmentary keratitis. Significant histopathologic findings in all dogs included mild lymphoplasmacytic gastroenteritis, steroid hepatopathy, and corneal epithelial thinning. One dog had moderate interstitial nephritis and pyelitis. CONCLUSIONS: In this experimental model, a CAP-CsA-prednisolone immunosuppressive regimen was effective in preventing rejection of allografts in DEA-mismatched dogs. Severe, unpredictable neurotoxicity and variable ocular toxicity significantly limit clinical applications at this time. CLINICAL RELEVANCE: A CAP-CsA-prednisolone protocol is an effective, oral immunosuppressive regimen for prevention of allograft rejection in DEA-mismatched mongrel dogs. For clinical application, identification of patients susceptible to toxic side effects would be necessary.     

Comparative efficacy of four commercially available heartworm preventive products against the MP3 laboratory strain of Dirofilaria immitis

A controlled laboratory study was conducted to evaluate the efficacy of four commercial products administered as a single treatment for the prevention of heartworm disease caused by Dirofilaria immitis in dogs. Forty-four commercially sourced Beagle dogs, 6-7 months of age, were received at the test site (Auburn University, Department of Pathobiology) on Study Day (SD) -72 to begin acclimation. On SD -30, each dog was inoculated subcutaneously with 100 infective, third-stage D. immitis larvae (MP3 strain, TRS Laboratories, Inc., Athens, GA). On SD -1, 40 dogs weighing 18.2-25.3 lbs were ranked by decreasing body weight and randomized to five groups of eight dogs each. On SD 0, the dogs assigned to Group 1 were treated orally with ivermectin/pyrantel pamoate chewable tablets, Group 2 dogs were treated orally with milbemycin oxime flavored tablets, Group 3 dogs were treated with selamectin topical solution, and Group 4 dogs were treated with imidacloprid/moxidectin topical solution. Group 5 dogs remained nontreated. Dosages for dogs in Groups 1-4 were based on the individual body weight of each dog and current labeled dose banding for each commercial product. All dogs were fasted overnight prior to treatment. Food was returned four hours after treatment. Animals were observed for abnormal clinical signs involving eyes, feces, respiration, behavioral attitude, locomotion/musculature, or skin conditions at prescribed intervals immediately after treatment and at twice daily intervals thereafter. On SD 90, whole blood was collected and tested for adult heartworm antigen. On SDs 119/120, the dogs were euthanized and subjected to necropsy examination for recovery of adult D. immitis and/or worm fragments. At necropsy, all 8 dogs in the nontreated group were infected with adult D. immitis (34-70 worms/dog, geometric mean (GM)=51.6 worms/dog). One or more adult D. immitis and/or worm fragments were recovered from 7 of 8 of the dogs each in Groups 1-3 (87.5% were heartworm positive). The respective GM worm burdens/dog for Groups 1-3 was 2.3, 2.4, and 2.3 which resulted in 95.6, 95.4 and 95.5% efficacy, respectively. No worms were recovered from any of the 8 dogs in Group 4 resulting in 100% efficacy.     

Effect of immunosuppressive drug therapy on blood urea nitrogen concentration in dogs with azotemia

Azotemic dogs receiving prednisone and azathioprine to enhance renal allograft survival had higher blood urea nitrogen (BUN):serum creatinine (SC) ratios, when compared with nontreated dogs with induced azotemia. The difference in ratios probably was attributable to increased BUN content secondary to the catabolic effects of the drugs used. However, dogs with naturally occurring renal failure had BUN:SC ratios that were similar to those for dogs receiving the catabolic drugs. It was concluded that even though catabolic drugs may influence BUN:SC ratios, the multiplicity of other factors affecting BUN and SC may interact to cause a wide range of BUN:SC ratios under conditions of naturally occurring primary renal failure in the dog.     

Lesions in dogs following renal transplantation and immunosuppression

Renal allografts were transplanted into 20 dogs (12 beagles, eight mongrels) following a prescribed protocol for pre-transplantation blood transfusions and kidney exchange. Immunosuppressive therapy (azathioprine and prednisone) was modified as needed for each dog. Seven of the beagle dogs survived for 1 year and were then euthanized; all other dogs died or were euthanized prior to 1 year post-transplantation. Graft rejection and renal failure were the greatest causes of mortality. Renal lesions which contributed to the death of some animals included renal vein thrombosis, nephrosis, and pyelonephritis. Inflammation of the lower respiratory tract (bronchitis, pneumonia, and pleuritis) was a contributory cause of death in some dogs. Cystitis and ureteritis occurred in almost half of the dogs. Prostatitis was seen in six of the 16 male dogs. Adrenal cortical atrophy, parathyroid gland hyperplasia, and bone marrow hypocellularity were seen in a majority of the dogs which survived 1 year.     

Effects of a thromboxane synthetase inhibitor on established immune complex glomerulonephritis in dogs.

Twelve Beagles were inoculated with concanavalin A, and after a mean ninefold increase in antibody titer, 1 mg of concanavalin A was infused into each renal artery of each dog to induce in situ immune complex glomerulonephritis. Starting 4 weeks after renal arterial infusion, 6 dogs were treated orally 3 times daily with 30 mg of 3-methyl-2 (3 pyridyl)-1-indolectanoic acid (CGS 12970)/kg of body weight, a thromboxane synthetase inhibitor, and 6 dogs (control group) received a gelatin capsule 3 times daily. Endogenous creatinine clearance and 24-hour urinary excretion of protein and thromboxane B2 were determined for each dog prior to renal arterial infusion, at the initiation of treatment and at 2, 4, 6, and 8 weeks after initiation of treatment. In addition, methyoxy-3H inulin clearance was determined at initiation of treatment and 4 and 8 weeks later. Renal specimens were examined histologically at the initiation of treatment and 4 and 8 weeks later. Glomerular mononuclear profiles/microns 3 were determined from at least 10 equatorially sectioned glomeruli from each dog. Paired t tests were used to compare mean values at the various time points to the respective mean baseline value and 2-sample t tests were used to evaluate differences between treatment groups. At the start of treatment (4 weeks after renal arterial infusion of concanavalin A), histologic evaluation of renal specimens revealed glomerular epithelial crescent formation, mononuclear cell proliferation, and infiltration of neutrophils. Mononuclear cell profiles and urinary excretion of protein and thromboxane B2 were significantly increased, but endogenous creatinine clearance values were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adrenocortical suppression in dogs on daily and alternate-day prednisone administration

Three groups of eight normal dogs each were orally given prednisone at doses of 0.22 mg/kg of body weight/day, 0.55 mg/kg/day, or 1.1 mg/kg on alternate mornings. Four dogs served as nontreated controls. Samples were obtained from members of each group to determine baseline serum cortisol and ACTH-stimulated cortisol values and histologic features in the lateral thoracic skin before prednisone administration, and after 1, 2, 3, and 4 weeks of administration. Some animals from each group were necropsied after 1, 2, 3, and 4 weeks of prednisone administration. Each course of prednisone administration resulted in adrenocortical atrophy and hypofunction, but adrenocortical suppression was less severe and slower in onset in the group given prednisone on alternate days. Extra-adrenal effects observed were atrophy of the skin and focal, fatty change of the liver. These changes were most evident in dogs given daily pharmacologic doses of prednisone (0.55 mg/kg/day). Fewer extra-adrenal effects were observed in dogs given alternate-day therapy. There were no extra-adrenal lesions in the dogs given equivalent glucocorticoid replacement doses (0.22 mg/kg/day).     

Gingival overgrowth in dogs associated with clinically relevant cyclosporine blood levels: observations in a canine renal transplantation model

Objective— To investigate the development of gingival hyperplasia in dogs after renal transplantation and administration of microemulsified cyclosporine A (MCsA).
Study Design— Experimental study.
Animals— Healthy adult mongrel dogs (n=5).
Methods— As part of study on renal transplantation, dogs administered MCsA (20 mg/kg/day), azathioprine, and prednisolone to prevent graft rejection were monitored for development of gingival changes. Prednisolone was discontinued after 3 months. MCsA dose was adjusted to maintain whole blood trough concentration of 400–700 ng/mL. Gingival change was evaluated by weekly examination and photodocumentation, and gingival biopsy for histopathology was performed at 28 weeks.
Results— One dog was lost because of acute graft rejection. Gingival hyperplasia developed in 3 of 4 dogs. The earliest gingival changes occurred in the interdental papillae at 20 weeks after transplantation. On histopathology, the underlying connective tissue was thickened and contained increase numbers of fibroblasts and inflammatory infiltrates.
Conclusions— Long-term immunosuppression with an MCsA-based treatment likely induces substantial gingival hyperplasia when therapeutic, immunosuppressive blood levels of MCsA were maintained for 32 weeks.
Clinical Relevance— MCsA is used for immune-mediated diseases and preventing rejection after transplant in dogs. MCsA blood levels, and gingival hyperplasia should be monitored by routine examination of the interdental papilla in dogs administered MCsA for long periods.     

Treatment of immune-mediated hemolytic anemia in dogs with cyclophosphamide

A review of 60 cases of immune-mediated hemolytic anemia (IMHA) in the dog was performed in order to characterize the disease and to identify potential prognostic indicators. Dogs ranged in age from 1 to 13 years, with a mean age of 6.5 years. The 2 most commonly affected breeds were Cocker Spaniels and Labrador Retrievers. Fifty-two of the 60 dogs tested (87%) were autoagglutination positive and spherocytes were present in 45 (75%). Forty-one (89%) of 46 patients tested positive for the presence of immunoglobulin on the red blood cell surface (Coombs assay). The most common clinical signs at presentation were lethargy, weakness, pale mucous membranes, icterus, hemoglobinuria, and anorexia. PCV less than 25% was present in 59 (98%) dogs. At the time of presentation, 35 dogs (58%) had a nonregenerative anemia, whereas 25 patients (42%) had a regenerative response. Thrombocytopenia was seen in 41 (68%) dogs. Nine of 34 dogs (26%) had a prolonged prothrombin time, 19 of 34 (56%) had a prolonged activated partial thromboplastin clotting time, and 12 of 34 (35%) had abnormal fibrinogen concentrations. All dogs received prednisone at immunosuppressive doses (2.2-4.4 mg/kg PO as a single or divided dose every 24 hours) and cyclophosphamide as primary therapy. Forty-one dogs (63%) received cyclophosphamide at 50 mg/m2 q24h for 4 days, whereas 9 dogs (15%) received an initial high dose (200 mg/m2) followed by 3 days of a lower dose (50 mg/m2 q24h). No statistical difference in survival times was found for either protocol. Thirteen dogs were treated with azathioprine in addition to cyclophosphamide and prednisone. The median survival time of dogs that received all 3 drugs was 370 days as compared to 9 days for those dogs that were treated with cyclophosphamide and prednisone alone. Thirty-one (52%) dogs died from the disease, 13 (22%) dogs were alive, and 15 (25%) dogs were lost to follow-up. The median length of survival for all dogs was 21 days. Eight dogs that were discharged from the hospital suffered a relapse (PCV < 25%).     

Effects of flunixin and flunixin plus prednisone on the gastrointestinal tract of dogs

Flunixin meglumine has been reported to induce gastrointestinal lesions in dogs when administered at therapeutic dosages. We administered flunixin meglumine to dogs daily for 10 days to assess the effect of this drug on the gastrointestinal tract. We also evaluated the possibility of corticosteroid potentiation of gastrointestinal toxicosis by concurrent administration of prednisone to 1 group of dogs. Dogs were monitored for gastrointestinal toxicosis by means of serial endoscopic evaluation, measurement of fecal occult blood, PCV, and total solid concentration, and by physical examination. There were 3 treatment groups of 5 dogs each. Group-1 dogs were given 2.2 mg of flunixin meglumine/kg daily, in 2 divided doses IM; group-2 dogs were given 4.4 mg of flunixin meglumine/kg daily, in 2 divided doses IM; and group-3 dogs were given 2.2 mg of flunixin meglumine/kg daily, in 2 divided doses IM plus 1.1 mg of prednisone/kg/d orally, in 2 divided doses. A fourth group of 5 dogs served as a control group. Endoscopically visible gastric mucosal lesions developed in all treated dogs within 4 days of initiating treatment. Lesions first developed in the gastric pylorus and antrum and lesions at these sites were more severe than those observed elsewhere. Dogs treated with flunixin meglumine plus prednisone developed the earliest and most severe lesions; lesion scores in group-2 dogs were higher than those in group-1 dogs. All dogs treated had occult blood in their feces by day 5 and its presence appeared to correlate more closely with endoscopic findings than did physical examination findings or changes in values for PCV or total solids.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Renal perfusion parameters measured by contrast‐enhanced ultrasound in healthy dogs demonstrate a wide range of variability in the long‐term

Contrast‐enhanced ultrasound may be helpful for detecting early renal microvascular damage and dysfunction in dogs. However, before this noninvasive imaging method can be tested as an early‐stage screening tool in clinical patients, an improved understanding of long‐term variation in healthy animals is needed. In this prospective, secondary, longitudinal, serial measurements study, variability of contrast‐enhanced ultrasound renal perfusion parameters was described for eight healthy dogs, using seven time points and a period of 83 weeks. Dogs were sedated with butorphanol (0.4 mg/kg), and contrast‐enhanced ultrasound of each kidney was performed after an intravenous bolus injection of a microbubble contrast agent (0.04 mL/kg). Time‐intensity curves were created from regions‐of‐interest drawn in the renal cortex and medulla. Intensity‐related parameters representing blood volume and time‐related parameters representing blood velocity were determined. A random‐effects model using restricted maximum likelihood was used to estimate variance components. Within‐dog coefficient of variation was defined as the ratio of the standard deviation over the mean. Time‐related parameters such as time‐to‐peak, rise and fall time had lowest within‐dog variability. Intensity‐related parameters such as peak enhancement, wash‐in and wash‐out area under the curve, total area under the curve, and wash‐in and washout rates had high within‐dog variability (coefficient of variation > 45%). Authors therefore recommend the use of time‐related parameters for future studies of renal perfusion. Within‐dog variability for bilateral kidney measurements was extremely low, therefore contrast‐enhanced ultrasound may be particularly useful for detecting unilateral changes in renal perfusion. Future studies are needed to compare contrast‐enhanced ultrasound findings in healthy dogs versus dogs with renal disease.