Treatment of a Myasthenic Dog with Mycophenolate Mofetil

A ten‐year‐old, male castrated Springer Spaniel was presented for dysphagia, ptyalism, and regurgitation. Evidence of megaesophagus and mild aspiration pneumonia were apparent on thoracic radiographs. A diagnosis of focal acquired myasthenia gravis was suspected and subsequently confirmed with a positive serum acetylcholine (ACh) receptor antibody concentration (3.87 nM/L). A gastrostomy tube was placed shortly after presentation; food and drugs (including azathioprine) were administered through the tube. After transient improvement, the dog suddenly deteriorated clinically, experiencing frequent episodes of regurgitation and developing severe aspiration pneumonia. Mycophenolate mofetil (MMF), a novel immunosuppressive drug with relative specificity for lymphocytes, was instituted every twelve hours via the gastrostomy tube. Within four days of beginning MMF therapy, both clinical evidence of pharyngeal/esophageal dysfunction and radiographic evidence of megaesophagus had resolved. Initially, clinical side‐effects of combined MMF/AZA administration were not apparent, but the patient experienced several vomiting episodes during the third week of treatment. The vomiting resolved after decreasing the dose of both drugs. The patient made a full recovery, and a one‐month follow‐up ACh receptor antibody concentration was normal (0.26 nM/L). After one month of combination therapy, the patient was weaned off of AZA and maintained on MMF as the sole immunosuppressive drug. The dog was subsequently weaned off of MMF on two occasions. Mycophenolate mofetil was reinstituted after the first discontinuation due to the development of profound appendicular muscle weakness two days after stopping MMF; the weakness resolved within 24 hours of reinstituting MMF. A positive ACh receptor antibody concentration (0.89 nM/L) after the second MMF weaning prompted the second reinstitution of MMF. Two months following this second MMF reinstitution, the dog was again serologically negative (0.51 nM/L) for myasthenia gravis. At the time of last followup, the dog remained in clinical remission eight months after initial presentation. The use of MMF to treat acquired myasthenia gravis in dogs has not been reported previously. The literature concerning MMF and its potential use in treating patients with autoimmune diseases is discussed.     

En bloc ligation of the thoracic duct in twelve dogs with idiopathic chylothorax

Twelve dogs with idiopathic chylothorax were treated by en bloc ligation of the thoracic duct. Six dogs recovered completely. Minimal follow-up in this group was 12 months. Five dogs were euthanized within 5 months of surgery because of persisting liquothorax: two with chylous and three with non-chylous effusions. One dog was euthanized 2 months after surgery because of a recurrence of dyspnoea. It is concluded that the results are comparable with those of a previously described surgical treatment; however, the technique described here is less complicated because it does not require mesenteric lymphangiography.     

A Surgical Approach to the Canine Olfactory Bulb for Meningioma Removal

Olfactory bulb lesions were diagnosed in four dogs presented for generalized seizure disorders. Surgery was performed on each dog using a transfrontal craniotomy. A free fascial-fat graft was used to cover the dural defect resulting from surgery. No major complications were observed during the immediate postoperative period. The histopathologic diagnosis in each case was meningioma. Generalized seizures recurred in all dogs, and three dogs were euthanized for this reason from 9 to 29 weeks postoperatively. One dog was euthanized 12 weeks after surgery due to pancreatitis and pneumonia. Necropsy showed that two dogs had recurrent olfactory bulb meningiomas, one dog had a meningioma of the opposite olfactory bulb, and one dog was tumor free.     

SPONTANEOUS PNEUMOPERITONEUM SUBSEQUENT TO GASTRIC VOLVULUS IN TWO DOGS

In two dogs spontaneous pneumoperitoneum developed following gastric volvulus. The pneumoperitoneum resulted from splenic necrosis and Klebsiella pneumoniae peritonitis in one and from a gastric perforation near the gastroesophageal junction in the other. The first dog was successfully treated by splenectomy, abdominal lavage, and systemic antibiotic therapy; the other was treated by closure of the perforation, tube gastrostomy, abdominal lavage, and systemic antibiotic therapy. One dog was euthanized four weeks after surgery because of metastatic cancer, and the other was euthanized six weeks after surgery due to recurrence of abdominal distention and peritonitis.     

Application of therapeutic plasma exchange in dogs with immune-mediated thrombocytopenia

Therapeutic plasma exchange (TPE) is an emerging treatment for dogs with immune-mediated diseases, but reports for treatment of immune-mediated thrombocytopenia (IMT) are lacking. These case reports illustrate the application of centrifugal TPE in 4 dogs with IMT. All dogs presented with severe hemorrhage requiring ≥1 blood transfusions, were unresponsive to conventional treatment or both. Dogs were treated with 3 sequential centrifugal TPE sessions, totaling 4.0 to 4.9 total plasma volumes exchanged per dog. In 3 dogs, TPE was associated with improvement in clinical manifestations of bleeding and platelet count in combination with immunosuppressive drugs. One dog was euthanized after 3 treatments because of persistent severe thrombocytopenia and hemorrhage. Preliminary observations indicate that TPE is safe and may be a useful adjunct in the management of IMT that is severe or refractory to traditional treatment.     

Iatrogenic brainstem injury during cerebellomedullary cistern puncture

Cerebrospinal fluid collection is fundamental to the investigation of central nervous system disorders although it carries potential risks. Herein we report the clinical signs and magnetic resonance (MR) imaging findings associated with needle injury to the brainstem during cerebellomedullary cistern puncture in four dogs. Three dogs were nonambulatory tetraparetic with cranial nerve deficits and one dog had unexplained left thoracic limb paresis. In MR images, there were conspicuous T2 hyperintensities in the myelencephalon in all dogs. In T2* gradient echo images, the lesions were hypointense in two dogs with multiple cranial nerve deficits, and hyperintense in another dog. One dog was euthanized due to sudden neurologic deterioration 12 days later, one died shortly after MR imaging, and a third was euthanized due to concurrent cervical spondylomyelopathy. The fourth dog recovered gradually. Diagnosis was confirmed histopathologically in one dog and was presumptive based on clinical signs and MR findings in three dogs. None of the dogs with cranial nerve deficits recovered, only the one dog with left thoracic limb paresis and concurrent syringomyelia.     

Cisplatin Therapy in 41 Dogs With Malignant Tumors

Forty-one dogs with a variety of histopathologically diagnosed, measurable tumors were treated with cisplatin (cis-diamminedichloroplatinum, Platinol, Bristol Laboratories, Syracuse, NY 13221-4755) as a single agent at a dosage of 60 mg/m2 given intravenously at 3-week intervals. In an attempt to avoid renal toxicity of cisplatin, saline diuresis was induced and maintained for 4 hours before and 2 hours following cisplatin administration. The dogs received one to ten doses of cisplatin. To determine response to therapy and to monitor toxicity of the drug, the dogs were evaluated with physical examinations including tumor measurements, radiography, complete blood counts, platelet counts, urinalyses, serum urea nitrogen concentrations, and serum creatinine concentrations. An overall response rate of 19% was observed. Complete remission occurred in one of 11 dogs with squamous cell carcinomas and one of one dog with a mediastinal undifferentiated carcinoma. Partial remissions were documented in one of 11 dogs with squamous cell carcinomas, two of three dogs with metastatic osteosarcomas, one of three dogs with nasal adenocarcinomas, and one of one dog with a thyroid adenocarcinoma. Toxic side effects were primarily gastrointestinal in nature, with vomiting occurring 1-6 hours after cisplatin administration in 27 of 41 dogs. Severe anorexia occurred in three dogs, and hemorrhagic diarrhea was observed in one dog. One dog developed grand mal seizures and died 3 hours following therapy. Granulocytopenia was documented in six dogs, and thrombocytopenia was observed in four dogs. One dog showed an increase in serum urea nitrogen and creatinine concentrations, but this patient had known pre-existing renal disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

EMPHYSEMATOUS CHOLECYSTITIS IN THE NONDIABETIC DOG: THREE CASE HISTORIES

Emphysematous cholecystitis not associated with diabetes mellitus was diagnosed in three dogs. All three dogs were examined because of vomiting. Neutrophilia, elevated serum alkaline phosphatase, and normal serum glucose were present in each animal. A gas-filled gallbladder and pericholecystic gas were seen radiographically in all three dogs; a cholecystolith was present in one dog. A cholecystectomy was performed on two dogs. Cultures of bacteria from these two bladders revealed Clostridium sp. One of these dogs was euthanized because of acute renal tubular necrosis that was diagnosed after ten days of treatment with gentamicin. The second dog recovered without incident. The third dog was treated successfully with antibiotics.     

Bile duct obstruction secondary to chronic pancreatitis in seven dogs

Seven icteric dogs were determined to have bile duct obstruction secondary to chronic pancreatitis. All dogs had histories of intermittent vomiting and diarrhea. Alkaline phosphatase and alanine aminotransferase activities and total bilirubin concentrations were markedly elevated. Diagnosis was based on exploratory laparotomy and histological examination. Each dog had a 3 to 10 cm mass in the body of the pancreas and obstruction of the common bile duct. Three dogs treated with pancreatectomy, gastrojejunostomy, and cholecystojejunostomy died within five weeks. Three dogs treated with conservative surgical procedures were alive at 8, 16, and 26 months postoperatively. One dog was euthanized because of suspected neoplasia. Hepatic enzyme activity and bilirubin levels decreased markedly in the surviving dogs. Histological examination of the pancreatic masses indicated chronic pancreatitis. Hepatic biopsies revealed evidence of cholestasis. Chronic pancreatitis should be included in the differential diagnoses of icterus, bile duct obstruction, and masses in the pancreas.     

Vinblastine and prednisolone as adjunctive therapy for canine cutaneous mast cell tumors

Twenty-seven dogs with inadequately excised, cutaneous mast cell tumors (MCT; 20 residual microscopic disease, seven marginal excision) were treated with a vinblastine and prednisolone chemotherapeutic protocol. Twenty dogs were available for follow-up examination after 12 months. One dog suffered local recurrence of the tumor, four dogs developed new cutaneous tumors, and one dog had both events. Fourteen dogs were free of MCT. There was no confirmed tumor-related mortality. Although toxicity from the chemotherapy was generally mild, one dog died of sepsis during treatment.     

Surgical treatment of tracheal collapse using pliable total ring prostheses: results in one experimental and 4 clinical cases

Pliable total ring prostheses were created from the polyvinyl chloride drip chambers of intravenous administration sets. The total ring prostheses were placed in one clinically normal research dog and in 4 client-owned dogs diagnosed with tracheal collapse. The research dog was euthanized one month after placement of the prostheses. Histopathological analysis of the trachea adjacent to the prostheses revealed a mild inflammatory response. The follow-up period for the clinical cases was from 4 months to 11 years. Radiographs taken and fluoroscopy performed 1 day to 5 months after surgery revealed improvement or resolution of the tracheal collapse. One dog was asymptomatic 28 weeks following surgery. Two dogs died 7 and 9 years after surgery, with one requiring intermittent medical management for coughing. They were euthanized for nonrespiratory illness. One dog had a persistent nonproductive cough, due to collapse of the mainstem bronchi, when last evaluated 4 months postoperatively. Pliable total ring prostheses provided adequate stability to the trachea and had the advantage of conforming to the trachea and being easy to create, place, and suture.     

Severe gastrointestinal bleeding secondary to lornoxicam in the dog

Six dogs with lornoxicam induced severe gastrointestinal bleeding are described. The ingested dose ranged between 0.5 - 5.1?mg/kg BW (median 0.63?mg/kg BW). The severity of the bloodloss anemia was moderate to severe with PCV values ranging between 12 - 27 % (median 16 %) and serum albumin concentrations between 12 - 22 g/l (median 16 g/l). One dog had evidence of chronic thrombocytopathia over 13 days and clinicopathologic findings of gastrointestinal bleeding over 55 days. None of the dogs developed kidney injuries. The clinical condition required transfusion of blood products in 5 of 6 cases. One dog with a perforated duodenal ulcer and septic peritonitis survived until discharge but had to be euthanized later on due to recrudescent clinical signs (hematemesis, melena). The median length of hospitalisation was 12 days (5 - 14). No correlation was seen between the ingested dose and severity of clinical signs. Lornoxicam ingestion leads to severe and longlasting gastrointestinal bleeding in the dog and requires immediate intensive therapy.     

Treatment of five haemodynamically stable dogs with immune‐mediated thrombocytopenia using mycophenolate mofetil as single agent

Five dogs were presumptively diagnosed with immune‐mediated thrombocytopenia. As they had all been chronically treated with non‐steroidal anti‐inflammatory drugs, administration of immunosuppressive doses of corticosteroids was considered contraindicated. Non‐steroidal anti‐inflammatory drugs were temporarily discontinued in all the dogs and mycophenolate mofetil was introduced as first‐line single immunomodulatory therapy. This treatment protocol resulted in complete remission of immune‐mediated thrombocytopenia in all the dogs, and mycophenolate mofetil was discontinued after several months of therapy in four of the five dogs with no relapses, even when non‐steroidal anti‐inflammatory drug administration was resumed. The remaining dog required continued mycophenolate mofetil therapy to avoid relapse. One dog experienced diarrhoea, and another dog had diarrhoea and decreased appetite .     

Diagnosis of canine claw disease – a prospective study of 24 dogs

The aetiology of claw disease in 24 dogs exhibiting only claw disease was investigated with cytologic examination of claw exudate, complete blood count (CBC), serum biochemistry panel, urinalysis, total thyroxine (tT4) concentration, antinuclear antibody (ANA) titre, bacterial culture and sensitivity testing, fungal culture, histopathology of claw biopsy samples and elimination diet. Abnormalities on the CBC, serum biochemistry panel and urinalysis were minor and nonspecific. Total T4 concentrations were within the normal laboratory reference range. Fungal cultures and ANA titres were negative in all dogs. A bacterial infection was present in approximately half of the dogs. On histological examination of claw tissue, a cell-poor or cell-rich interface onychitis was seen in all but one dog. Evidence for an adverse reaction to food was present in four dogs. One dog responded completely to antibiotic therapy. Interface onychitis seems to be a histological reaction pattern of the claw matrix in the dog with various possible underlying aetiologies. In dogs with claw disease as the only clinical sign, the recommended initial diagnostic evaluation includes cytologic examination, bacterial culture and sensitivity, claw biopsy and an elimination diet.     

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.     

Citrobacter freundii septicemia in two dogs.

A 4-month-old Maltese puppy and a 7.5-year-old Collie were diagnosed with septicemia associated with Citrobacter freundii. The puppy died soon, after developing weakness and mucohemorragic diarrhea. The Collie had immune-mediated hemolytic anemia and thrombocytopenia and was treated with immunosuppressive drugs before being euthanized. Gross examination of the puppy revealed mucohemorrhagic intestinal contents. Focal necrotic hepatitis, fibrinous peritonitis, interstitial pneumonia, and hemorrhagic gastrointestinal contents were observed in the older dog. Histologically, there was a diffuse, moderate, histiocytic meningitis in the puppy and a focal fibrinonecrotic hepatitis in the adult dog. Lesions in both dogs contained numerous gram-negative rods. Citrobacter freudii is a potential cause of monomicrobic bacteraemia-septicemia in puppies or immunocompromized adult dogs.The gastrointestinal tract is probably the main site of entry.     

Treatment of severe immune-mediated thrombocytopenia with human IV immunoglobulin in 5 dogs

BACKGROUND: Glucocorticoids with or without other immunotherapy are the initial treatment of choice for dogs with severe immune-mediated thrombocytopenia (IMT). The majority of treated dogs will have improvements in platelet counts within 5 to 7 days of starting therapy, but complications from hemorrhage often occur before a response is seen. Human IV immunoglobulin (hIVIG) blocks Fc receptors on mononuclear phagocytic cells in dogs; it is used in people with idiopathic thrombocytopenic purpura. HYPOTHESIS: The purpose of this study was to describe adverse effects and benefit of hIVIG in addition to conventional immunosuppressive therapy in dogs with severe IMT. ANIMALS: Five client-owned dogs with severe primary IMT. METHODS: Case series. The hospital database was searched for dogs with primary IMT treated with hIVIG. RESULTS: No adverse effects were noted during or after hIVIG infusion in any treated dog. Over a 6-month follow-up, all dogs were clinically normal when using conventional immunosuppressive therapy. Human IVIG was administered 3 days after initiation of immunosuppressive therapy in 4 dogs, and, after 2 days, in 1 dog. In all dogs, the mean platelet counts pre- and 24 hours post-hIVIG infusion (0.28-0.76 g/kg) were 2,500/pL and 50,600/microL (62,750/microL for the 4 responders), respectively. One dog failed to respond as promptly to hIVIG (0.34 g/kg), and the platelet count increased to 66,000/microL after 9 days of immunosuppressive therapy. The mean duration of hospitalization post-hIVIG in all 5 dogs was 1.8 days (12 hours for responders), and the mean total length of hospitalization was 4.6 days (3.5 days for responders). Active hemorrhage resolved and no packed red blood cell transfusions were required after hIVIG infusion for responders. CONCLUSIONS AND CLINICAL IMPORTANCE: Human IVIG was well tolerated and appeared to be associated with rapid platelet count recovery and amelioration of clinical signs in most dogs with IMT.     

A Clinico-pathological study on the effect of vincristine on transmissible venereal tumour in dogs

Transmissible venereal tumour (TVT) is a coitally transmitted neoplasm of dogs and is common among sexually active dogs, where sexual behaviour is not under control. Several treatment options are available for the treatment of the tumour, with chemotherapy being the most commonly employed. In this study, we investigated the clinical and cytological changes after weekly vincristine sulphate administration in 38 cases of naturally occurring TVT. Tumours totally regressed in 31 dogs after two to seven doses (mean 3.54 +/- 1.01) of vincristine. One dog died after the fifth dose of vincristine, and in six dogs, an additional treatment with doxorubicin was needed. Masses were still present in four dogs and the histopathological examination revealed small nodules of granulation tissue in two dogs, while viable tumour cells were identified in the remaining two cases. No recurrences were observed in a follow-up period of 7-49 months (mean 13.64 +/- 9.66); in one dog, granulation tissue was detected in the surgery site after 2 months. Treatment success could easily be followed by the cytological changes. In conclusion, vincristine was found to be effective chemotherapeutic agent.     

Results of transthoracic esophagotomy retrieval of esophageal foreign body obstructions in dogs: 14 cases (2000-2004)

The records of 14 consecutive cases of esophageal foreign body obstruction in dogs that had undergone transthoracic esophagotomy for foreign body retrieval were reviewed. Clinical results were considered successful in 13 of 14 dogs. One dog was euthanized at surgery because of the severity of associated thoracic lesions. Clinical signs resolved in the remaining 13 dogs. Two dogs had postoperative complications. One dog developed a pyothorax, and one dog developed a subcutaneous seroma. The overall recovery rate was 93%.     

Phase I Evaluation of Doxorubicin and Whole-body Hyperthermia in Dogs with Lymphoma

Fifteen previously untreated dogs with histologically confirmed, high-grade multicentric lymphoma were entered into a phase I study to evaluate combined doxorubicin and whole-body hyperthermia (DOX/WBH). Groups of three, four, and eight dogs were treated with whole-body hyperthermia and concurrent doxorubicin at 12 mg/m2, 24 mg/m2 and 30 mg/m2, respectively, after one doxorubicin induction dose at 30 mg/m2. Plateau temperature (42 +/- 0.1 degree C) was maintained for 90 minutes using a radiant heating device. A total of five DOX/WBH treatments per dog were planned, and these were given every 21 days. Treatment-related toxicity was not seen in the 12-mg/m2 doxorubicin dose group. Tumor progression prohibited administration of more than three DOX/WBH treatments to any dog in the 12-mg/m2 group. Premature ventricular contractions developed after the fifth treatment in one of the four dogs treated with 24 mg/m2 of doxorubicin. Two dogs (25%) in the 30-mg/m2 dose group had treatment-related toxicity. One dog experienced acute serious myelosuppression 1 week after the third treatment. This dog received all planned DOX/WBH treatments. Asymptomatic cardiac toxicosis consisting of decreased ejection fraction and fractional shortening developed in the second dog. This dog received only two DOX/WBH treatments. The three dogs treated at 12 mg/m2 had partial responses of short duration (60-83 days). Four dogs treated at 24 mg/m2 had complete responses for 150, 164, 186, and 200 days. Eight dogs treated at 30 mg/m2 had complete responses with a mean and median duration of 241 and 190 days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)