Evaluation of lung pathology in Dirofilaria immitis-experimentally infected dogs treated with doxycycline or a combination of doxycycline and ivermectin before administration of melarsomine dihydrochloride

Adulticide therapy in heartworm (Dirofilaria immitis)-infected dogs can lead to thromboembolism, which can seriously compromise post-treatment health status. Lung pathology following adulticide therapy was evaluated in three groups of experimentally infected dogs. Group 1 was treated with doxycycline at 20 mg/kg per os once daily for 30 days post infection followed by an intramuscular injection of melarsomine dihydrochloride (2.5 mg/kg) at Week 12, followed 1 month later by two injections 24 h apart. Group 2 was treated as described for Group 1, with the addition of ivermectin at 6 mcg/kg given monthly per os for 24 weeks post-infection. Group 3 received melarsomine alone, as described above. All dogs were necropsied at Week 24 and lung pathology was evaluated. Lesion criteria included perivascular inflammation and endothelial proliferation. Lesions were scored by two independent pathologists who were blinded as to treatment. Results indicate that doxycycline treatment alone or combined with ivermectin had lower lesion scores than lungs from dogs who had received melarsomine alone. Dogs that received the combined doxycycline/ivermectin protocol and treated with adulticide showed less severe arterial lesions and the virtual absence of thrombi.     

Mortality associated with melarsomine dihydrochloride administration in two North American river otters (Lontra canadensis) and a red panda (Ailurus fulgens fulgens).

Two adult North American river otters (Lontra canadensis) and an adult red panda (Ailurus fulgens fulgens) at three separate institutions died within 22 hr after receiving single 2.5- to 2.7-mg/kg doses of melarsomine dihydrochloride administered in the epaxial musculature as a treatment for filarid nematodes. One otter had a suspected Dirofilaria immitis infection, the other had a confirmed D. lutrae infection, and the red panda had a confirmed Dirofilaria sp. infection, presumably with D. immitis. Postmortem examinations revealed similar gross lesions, although they were less severe in the red panda. The trachea and primary bronchi contained abundant foamy fluid, the lungs were mottled with areas of consolidation, and the pulmonary parenchyma exuded abundant fluid at the cut section. Histologic evaluation revealed acute pulmonary edema, which resulted in respiratory failure and death. There may have been direct pulmonary cellular toxicity of melarsomine dihydrochloride or a severe systemic anaphylactic reaction to antigens released after parasite death. An idiosyncratic drug reaction or a low therapeutic index of melarsomine probably caused the death of the three individuals. Melarsomine dihydrochloride use should be avoided in North American river otters and red pandas.     

Systemic Arterial Dirofilariasis in Five Dogs

Systemic arterial dirofilariasis is an unusual manifestation of heartworm disease of dogs that results from aberrant migration of Dirofilaria immitis into the peripheral arterial circulation. To expand the clinical characterization of systemic arterial dirofilariasis, 5 dogs evaluated at the North Carolina State University's College of Veterinary Medicine were reviewed. Common clinical presentations included hindlimb lameness, paresthesia of hindlimbs, and interdigital ischemic necrosis resulting from thromboembolic disease. Visualization of heartworms with angiography or ultrasonography confirmed the diagnosis in all cases. All 5 dogs were treated with an adulticide; 3 dogs were treated with thiacetarsamide sodium and 2 with melarsomine dihydrochloride. Four of the 5 dogs survived the initial treatment period; 1 dog died of severe thromboembolic complications after thiacetarsamide sodium therapy. The treatment of systemic arterial dirofilariasis creates a therapeutic challenge because of multiple potential complications resulting from thromboembolic disease.     

Wolbachia and its influence on the pathology and immunology of Dirofilaria immitis infection

Since the definitive identification in 1995 of the bacterial endosymbiont Wolbachia that resides in different tissues of the filarial worm Dirofilaria immitis, there has been increasing interest to understand whether and what role it plays in the pathogenesis of and immune response to heartworm infection. The present study evaluated the effects of treatments on lung pathology in 20 beagle dogs experimentally infected with D. immitis. Dogs in Group 1 were treated with doxycycline (10 mg/kg/day) orally from weeks 0-6, 10-12, 16-18, 22-26, and 28-34. Dogs in Group 2 served as infected, non-treated controls. Dogs in Group 3 were given doxycycline as described for Group 1 combined with weekly oral doses of ivermectin (6 mcg/kg) for 34 weeks and intramuscular (IM) melarsomine (2.5 mg/kg) at week 24, followed by two additional melarsomine injections 24h apart 1 month later. Group 4 received only melarsomine as described for Group 3. Lung lesion criteria, scored by two independent blinded pathologists, included perivascular inflammation and endothelial proliferation. Doxycycline treatment alone had no effect on lesion scores, whereas the combination of doxycycline and ivermectin resulted in less severe perivascular inflammation. All lungs were evaluated for positive immunostaining for the Wolbachia surface protein (WSP). Control dogs showed numerous thrombi, intense perivascular and interstitial inflammation and, occasionally, positive staining for WSP. Interestingly, dogs receiving doxycycline/ivermectin/melarsomine showed significantly less severe arterial lesions and the virtual absence of thrombi.     

Percutaneous heartworm removal from dogs with severe heart worm (Dirofilaria immitis) infestation

Canine heart worm disease is often life-threatening due to its various complications, including right side heart failure, caval syndrome and pulmonary eosinophilic granulomatosis. Several preventive medications and melarsomine have been developed and they are very effective to control heartworm infestation. However, in a case of severe infestation, melarsomine therapy often results in an unfavorable outcome because of the severe immune reaction caused by rapid killing of the adult worm. Surgical removal and an interventional method using flexible alligator forceps have been well described in the literature. Despite the usefulness of mechanical removal using flexible alligator forceps, the methodology still needs to be upgraded for increasing the applicability for treating dogs with severe infestation. We describe herein a newly developed percutaneous removal method for heartworms and this was successfully applied to 4 dogs with severe heartworm infestation. The follow-up studies also showed favorable outcomes with no complications.     

COMPLICATIONS OF METRIZAMIDE MYELOGRAPHY IN THE DOG: A SUMMARY OF 107 CLINICAL CASE HISTORIES

The case histories of 107 dogs undergoing metrizamide myelography at two veterinary hospitals were reviewed. Twenty-three variables, including body weight, injection site, dose of contrast medium, and medical complications during and after recovery from anesthesia, were submitted to statistical analysis by computer. Partial or generalized seizures were the most common medical complications, occurring in 54 percent of the dogs weighing more than 29 kg. Other less frequent medical complications were exacerbation of neurologic signs the day following myelography (11 percent), transient apnea during contrast medium injection (9 percent), vomiting (5 percent), hyperesthesia (3 percent), pyrexia (1 percent), and death (1 percent). The incidence of medical complications associated with metrizamide myelography in this study is higher than in previous reports. The most likely variables associated with seizures were high injection volumes and metrizamide injection at the cisterna magna. The preanesthetic administration of intramuscular pentobarbital did not significantly reduce seizure incidence. Seizures were controlled by anticonvulsant medication.     

Dirofilaria repens infection in a dog: diagnosis and treatment with melarsomine and doramectin

Therapy of canine dirofilariois due to Dirofilaria repens is indicated for dogs suffering from clinical signs of this disease, such as dermal swelling, sub-cutaneous nodules and pruritus. It is also important in order to decrease the risk of infection to other dogs and humans in the vicinity of the infected animal when suitable mosquito vectors are present. Combined therapy with the arsenic adulticide melarsomine and the avermectin microfilaricidal doramectin was effective in clearing infection with D. repens in a dog. The number of microfilariae dropped from 17 microl(-1) blood pre-treatment to 7 microl(-1) following the first adulticide injection and reached 0 a day after the microfilaricidal administration. The dog remained negative for D. repens microfilaremia during a follow-up period of 90 days. Euthanasia and necropsy performed 3 months after the initiation of therapy due to a progressive neoplastic disease revealed no evidence of filariae.     

Open versus closed bilateral anal sacculectomy for treatment of non-neoplastic anal sac disease in dogs: 95 cases (1969-1994)

OBJECTIVE: To determine complications associated with anal sacculectomy in dogs with non-neoplastic anal sac disease and compare complication rates for open versus closed techniques. DESIGN: Retrospective study. ANIMALS: 95 dogs. PROCEDURE: Medical records were reviewed for information on signalment, history, physical examination findings, type of anal sac disease, surgical technique (closed, standard open [surgery performed prior to 19801, or modified open [surgery performed after 19801), and postoperative complications. RESULTS: In 57 dogs, a closed technique was used, and in 38, an open technique was used. Only 3 dogs developed short-term complications (excessive drainage, scooting and inflammation, and seroma formation), and 14 developed long-term complications (continued licking of the surgery site, fecal incontinence, fistulation, and stricture formation). Development of postoperative complications was significantly associated with surgical technique. Dogs that underwent standard open sacculectomy prior to 1980 were 13.67 times as likely to have a long-term complication as were dogs that underwent closed sacculectomy. Weight of the dog, type of anal sac disease, age at the time of surgery, and whether the wound was closed surgically were not significantly associated with whether dogs developed postoperative complications. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that anal sacculectomy is a safe and effective treatment for non-neoplastic anal sac disease in dogs and is associated with a low rate of complications. The standard open technique was associated with the greatest number of complications, whereas complication rates for the closed and modified open techniques were similar to each other.     

Ultrasound-guided coxofemoral arthrocentesis in horses

REASON FOR PERFORMING STUDY: Coxofemoral joint pain is probably underestimated due to difficulties in identifying hip pain. The deep location of the joint and proximity of the sciatic nerve make arthrocentesis based on external landmarks a difficult and potentially risky procedure in mature horses. OBJECTIVES: To describe an ultrasound-guided injection technique of the coxofemoral joint in standing horses and to evaluate its accuracy and potential difficulties/complications. METHODS: Nine mature horses had both pelvic areas prepared for sterile ultrasound examination (3.5 MHz curvilinear probe). Coxofemoral joints were located and penetrated at their craniodorsolateral aspect under ultrasonographic guidance and injected with sterile contrast medium. A standing ventrodorsal radiographic view of each hemipelvis centred on the hip was obtained for each horse to assess the injection site. Horses were evaluated for 10 days following injection for possible complications. RESULTS: Intra-articular injection was successful in all 18 joints. The procedure was well tolerated by horses under minimal restraint. Mean +/- s.d. needle repositionings required before accurate placement was 1.5 +/- 1.3 per joint. Once the needle was in the joint, synovial fluid was obtained in 7/18 joints. Minimal periarticular contrast medium was detected in 2/18 joints. Mean +/- s.d. ultrasonographic examination time required for coxofemoral localisation, accurate needle positioning and injection was 4.3 +/- 2.1 min. No complications were observed in the 10 days following injection. CONCLUSION: The ultrasound-guided coxofemoral arthrocentesis is an accurate, reliable and safe technique that offers a real time evaluation of needle introduction into the deep and narrow coxofemoral joint space. POTENTIAL RELEVANCE: Although this technique remains to be tested on clinical cases, it is a promising tool to facilitate diagnosis of coxofemoral pain, septic arthritis or administration of intra-articular medication.     

A modified ventral fixation for surgical management of atlantoaxial subluxation in 19 dogs

OBJECTIVE: To describe a modified ventral stabilization technique for surgical management of atlantoaxial subluxation in dogs and to evaluate the outcome. STUDY DESIGN: Retrospective clinical study. SAMPLE POPULATION: Nineteen client-owned dogs. METHODS: Medical records of 19 dogs with a radiographic diagnosis of atlantoaxial subluxation surgically managed by a modified ventral fixation technique (cortical screws, Kirschner wires, polymethylmethacrylate) were reviewed. Data on pre- and post-operative neurologic status, surgical technique, and complications were retrieved. Follow-up evaluation was performed at approximately 1 month. Telephone interview of the owner was used for long-term assessment (median follow-up for 17 surviving dogs was 10.5 months). RESULTS: Adequate reduction and stabilization was achieved in all dogs based on radiographic assessment immediately after surgery. Improved neurologic outcome occurred in 16 dogs at 1 month and in 15 dogs at follow-up; 2 dogs died of post-operative complications within 24 hours of surgery. One dog was euthanatized at the owners' request because of recurrent neck pain associated with implant failure after 1 month. Two dogs required surgery to remove broken and migrated implants, but further stabilization was not necessary. CONCLUSIONS: Adequate stabilization and improved neurologic outcome was achieved in most dogs. However, on account of the small size of the study and the variable neurologic signs of the dogs on admission, the surgical technique described could not be compared to those previously reported. CLINICAL RELEVANCE: The surgical technique described is an effective means of surgical treatment for atlantoaxial subluxation.     

MYELOGRAPHY IN THE CAT

Metrizamide myelographic examinations were performed on five normal cats using sequential cisternal and lumbar injections at weekly intervals to determine the dose of contrast medium required, adverse effects, and quality of the myelographic study. The normal myelographic appearance in the cat is described. All spinal cords were examined histopathologically after the termination of the study, and variable mild lesions were found. Doses of 0.2 ml/kg, 0.35 ml/kg, and 0.4 ml/kg metrizantide, respectively, for lumbar, thoracolumbar, and complete spinal studies are recommended when performing lumbar injection. Recommended doses using cisternal injection for cervical, cervicothoracic, and complete spinal studies are 0.2, 0.45, and 0.5 ml/kg, respectively. Subjectively, lumbar injection produced higher-quality thoracolumbar myelograms and cisternal injection produced higher-quality cervical studies. Clinical complications during the study included one seizure following cisternal myelography and mild neurologic deficits in all cats, which resolved within 36–48 hours.     

Pathogenicity of Beauveria bassiana in mice.

The potential pathogenicity of Beauveria bassiana was examined by intramuscular injection of high (2 x 10(8)) or low (2 x 10(5)) concentrations of conidia spores, into the left or right quadriceps muscles of CD-1 mice, respectively. The injection sites were monitored over a period of 28 days by both microbiological and histopathological methods. Focal muscle necrosis, edema and inflammation occurred rapidly (within 12 hours) at the high dose application (2 x 10(8)) site, but such lesions were far less severe with the low dose spore application (2 x 10(5)). Fungal spores in the high dose site persisted in normal shape for 2 weeks, after which time they began to degenerate. Almost all spores were cleared from the injection site within the 28-day observation period. Spread to other organs of the body was not observed, except by macrophage transport to regional lymph nodes. At the low dose rate, most spores were cleared within 12 h to 2 d, leaving only mild focal edema and inflammation. Viable fungal colonies could be recovered up to 3 d after injection from the high dose site, but only up to 12 h from the low dose site. It was concluded that B. bassiana does not cause infection, nor multiply, nor survive for more than 3 days when injected intramuscularly into healthy mice.     

Intramuscular injection in the cat

The commonly adopted technique and site for intramuscular injection in the cat are described, and the often resulting inadequacy and risk are discussed. An alternative site and technique are suggested to ensure a more reliable effect when an intramuscular injection is indicated. Résumé. On décrit la technique et l'endroit communément adoptés pour injection intramusculaire chez le chat et on discute de l'imperfection et du risque qui résultent souvent. On suggère un endroit alternatif et technique pour s'assurer d'un effet certain quand une injection intramusculaire est indiquée. Zusammenfassung. Die gewǒhnlish angewendete Technik und Stelle fur intramuskulàre Injektionen in Katzen sind beschrieben und das oft folgende Versagen und Risiko wird diskut-iert. Eine andere Stelle und Technik sind vorgeschlagen, um einer zuverlǎssigeren Wirkung sicher zu sein wenn eine intramuskulàre Injektion erforderlich ist.     

Implantation of transponders at the bottom of the ear in equines

In the present work transponders of 2 identification systems have been implanted on an exactly defined site at the bottom of the ear on 28 horses. The Backhome system is easier to handle and less complicated than the trovan system since it is smaller and handier. The hemorrhages that had occurred after the injection were mild at 17 animals and moderate at 4 animals. Inflame changes at the injection site post application were limited to minor swellings (n = 3) and minor pain (n = 6). The interrogator's scope of the two transponder systems is different. The interrogator's scope of the trovan transponder was approximate 5 to 10 cm and of the Backhome transponder approximate 15 to 25 cm resulting in a higher benefit. All 14 slaughtered horses were examined pathologically in different periods and two transponders were found to have changed their sites considerably at approximately 8 to 10 cm compared with the initial injection site. The connective tissue surrounding the transponder was transparent and thin in cases where the transponder had been implanted 30 days ago or earlier, histopathologically the tissue thickness changed. Inflammatory changes appeared in 3 cases as a minor perivasculitis and in further 5 cases as a collection of single siderophages. In the remaining 5 cases no inflammation was determined. The minor changes and lack of inflammation reflect the high biocompatibility of transponders.     

Local tissue reaction to the administration of an inactivated Brucella ovis saline-in-oil vaccine by the intraperitoneal route

An inactivated Brucella ovis saline-in-oil vaccine was administered to 14 adult ewes using both the intraperitoneal route and the subcutaneous route. Pairs of animals were necropsied at intervals between 24 hours and ten weeks after injection. The nature of the local inflammatory reaction to the administration of the vaccine was similar at all sites. The lesion consisted of granulomatous inflammation arranged around droplets of oily vaccine. Diffuse peritonitis was seen at necropsy in 12 of the 14 animals. A local extraperitoneal inflammatory response at the injection site was present in four animals despite careful attempts to deposit the vaccine within the abdominal cavity. A second study of 30 rams vaccinated by the intraperitoneal technique confirmed that extraperitoneal deposition of vaccine commonly occurred and that approximately 20% of animals vaccinated by the intraperitoneal method still had peritonitis six months later.     

Copper-induced skeletal myopathy in rabbits.

Doses of 1.66 mg Cu/kg/day, as cupric acetate in aqueous solution, were injected intramuscularly into the lateral thigh muscles of rabbits. The rate of loss of Cu from the injection site was estimated from in vivo measurements of 64Cu injected on the 15th day. Biological half-life values were 1.0 h for the first component (accounting for 65.2% of the 64 Cu) and 14.6 h for the second component (34.8% of the 64Cu). For the control group, values were 0.8 h and 62.2%, 14.6 h and 37.8%. Grossly visible lesions of dermatitis were noted on the paws, i.e. at sites removed from the site of injection, in some rabbits injected with Cu acetate two days post injectionem (p.i.). Histologically detectable lesions of acute inflammation were seen as early as 24 hours p.i. at the injection site of rabbits which had been exposed to the Cu once. Multiple injections and longer time periods resulted in lesions of acute and chronic inflammation. Cu was detected by the use of rubeanic acid stain. Signs of muscle degeneration and regeneration were seen as early as three days p.i. in rabbits which had received two injections of Cu. Rabbits which had been killed six days p.i. after a single injection showed chronic inflammatory changes and newly formed myofibres. Rabbits which had been killed 37 days p.i. after 17 injections showed lesions of acute and chronic inflammation of muscle and surrounding connective tissue, as well as signs of muscle regeneration. The gangrene visible grossly was attributed to the ischaemia caused by conglomerations of Cu.     

Development of an injection site sarcoma shortly after meloxicam injection in an unvaccinated cat

A single dose of a rapidly-absorbed non-steroidal anti-inflammatory drug (NSAID) was injected into the subcutaneous tissue of the interscapular region of a 12.5-year-old cat. A mild swelling was noticed at the injection site 6 weeks later. This progressed into a 5 cm diameter mass which was removed 6 months after the injection had been given. An injection site sarcoma (ISS) was diagnosed histologically. As the cat had not been vaccinated for at least 12 years, the previous NSAID injection was considered to be a possible cause of the ISS. Inflammation is thought to be important in the development of ISS. If injection of a rapidly-absorbed NSAID can stimulate sufficient inflammation to promote the development of an ISS, other non-vaccine injections may also have the potential to influence ISS development. This suggests that injection of both vaccines and non-vaccine medications should be minimised to reduce the risk of ISS development.     

Granuloma formation associated with subconjunctival injection of a corticosteroid in dogs.

In three dogs given a subconjunctival injection of methylprednisolone acetate for the treatment of ophthalmic disorders, a yellow mass developed at the injection site. Microscopic examination of each excised mass revealed circumscribed granulomatous inflammation surrounding a central core of amorphous foreign material.     

Prevalence and significance of extracellular myelin‐like material in canine cerebrospinal fluid

Background: Myelin‐like material in canine cerebrospinal fluid (CSF) specimens has been attributed to demyelinating or myelomalacic conditions. In our experience, myelin‐like material is observed frequently, especially in lumbar samples, and in a variety of disease conditions. Objectives: The objective of this study was to determine if there are associations between the presence of myelin‐like material and CSF collection site, body weight, underlying disease, and patient outcome. Methods: Wright–Giemsa‐stained cytocentrifuged specimens of CSF from the cerebellomedullary cistern (n=51) and lumbar cistern (n=47) of 98 dogs with neurologic disease were evaluated retrospectively for the presence and amount of extracellular myelin‐like material. Results were compared based on collection site, body weight, type of neurologic disease, and outcome. Results: Myelin‐like material was observed in 20/98 (20%) samples and was more frequently observed in lumbar (17/47, 36%) than cerebellomedullary samples (3/51, 6%) (P=.0028). Samples from dogs <10 kg were more likely to contain myelin (14/36, 39%) compared with dogs ≥10 kg (5/60, 8%) (P=.0052). Larger amounts of myelin‐like material were observed in CSF from dogs with intervertebral disk disease compared with other diseases (P=.045). No association was found between myelin‐like material and outcome. Conclusion: The association of extracellular myelin‐like material in canine CSF samples with sampling site and body weight suggests it is more often an artifact of collection technique and anatomy rather than the result of neurologic disease. Myelin‐like material in CSF is not associated with a poorer prognosis.