Bone marrow-derived dendritic cell vaccination of dogs with naturally occurring melanoma by using human gp100 antigen

Canine malignant melanoma (CMM) is a common and aggressive form of cancer in dogs. Established therapeutic approaches such as surgery, chemotherapy, and radiation therapy (RT) have not proven curative. As a coadjuvant of RT and to enhance the antimelanoma immune response, we characterized dendritic cells (DCs) from the bone marrow (BM) of dogs with CMM, ex vivo, for use in therapeutic vaccines. BM mononuclear cells from 3 dogs with melanoma and from 1 healthy dog were cultured for 12 days in media supplemented with recombinant human granulocyte-macrophage colony stimulating factor, stem cell factor, tumor necrosis factor, and Flt-3 ligand. On day 11, DCs were transduced with an adenovirus vector encoding a xenoantigen, human melanoma antigen gp100. Each dog received 3 subcutaneous vaccinations over a 4-month period. Phenotypic analysis of the expanded DC population demonstrated expression of CD11c/CD18 and major histocompatibility complex class II surface markers, and ultrastructural features characteristic of DCs were observed on electron microscopy. On functional analysis, these DCs were able to stimulate allo-reactivity and capture and express gp100. One dog demonstrated antigen-specific cytotoxic T lymphocyte (CTL) activity in peripheral blood lymphocytes. This dog has displayed no clinical signs, either locally or systemically, of recurrent melanoma 48 months after initial DC injection. However, another dog, which was CTL negative, relapsed 22 months after vaccination. Ex vivo DC expansion is feasible for immunotherapy of spontaneous cancers in outbred dogs.     

Polymerase chain reaction screening for DNA viruses in paraffin-embedded brains from dogs with necrotizing meningoencephalitis, necrotizing leukoencephalitis, and granulomatous meningoencephalitis

The objective of this investigation was to determine whether or not herpesvirus (herpes-), adenovirus (adeno-), or canine parvovirus DNA is present in the brains of dogs with necrotizing meningoencephalitis (NME), necrotizing leukoencephalitis (NLE), and granulomatous meningoencephalitis (GME). Paraffin-embedded brain specimens from 12 histopathologically confirmed dogs with NME, 3 with NLE, and 7 with GME were screened for viral DNA with degenerate herpes- and adenovirus polymerase chain reaction (PCR) and a canine parvovirus-specific PCR. Positive-control specimens included genomic viral DNA and paraffin-embedded tissues from dogs with confirmed herpes-, adeno-, or canine parvovirus infections. Herpes-, adeno-, or canine parvovirus DNA was amplified by PCR from the corresponding positive-control specimens. Negative controls included 7 dogs with various brain disorders and produced no viral amplicons. The 22 dogs with NME, NLE, and GME were negative for viral DNA. Additional studies testing for other viruses or inherited genetic mutations are warranted to gain insight into the etiologies of NME, NLE, and GME. We discuss potential etiologies and provide a clinical and histopathologic overview of these common canine encephalitides.     

Clinical, histopathological and immunological characteristics of exfoliative cutaneous lupus erythematosus in 25 German short-haired pointers

Clinical, histopathological and immunological features of exfoliative cutaneous lupus erythematosus, an uncommon generalized exfoliative dermatitis occurring exclusively in German short-haired pointers, were characterized in 25 dogs. The disease affects young adult dogs and its familial incidence strongly suggests a hereditary origin. Lesions were characterized by scaling and alopecia affecting 100 (25/25) and 76% (19/25) of dogs, respectively. Follicular casts were present in 28% (7/25) of dogs. The muzzle, pinnae and dorsum were typically affected. Generalized skin lesions were described in 52% (13/25) of dogs. Systemic signs of pain and lameness affected several dogs. Anaemia and thrombocytopenia were detected in several dogs with a more severe clinical phenotype. The most common histopathological features were hyperkeratosis and a lymphocytic interface dermatitis. Direct immunostaining revealed IgG deposition in the epidermal and follicular basement membrane of 100 (19/19) and 41% (7/17) of dogs, respectively. Circulating antifollicular and antisebaceous gland IgG antibodies were demonstrated by indirect immunostaining in 57% (4/7) of dogs. This disease usually responds poorly to immunosuppressive therapy and it has a guarded prognosis. Where outcome was recorded, 85% (10/12) of dogs were euthanased due to either a failure to respond to, or complications associated with, immunomodulatory therapy. Two affected dogs are in remission and maintained on immunomodulatory dosages of prednisolone. This study demonstrates the existence of a cellular and humoral immune response directed against the epidermal basement membrane of dogs with exfoliative cutaneous lupus erythematosus. Additional studies are required to further characterize the immunological pathogenesis of this disease.     

Molluscicidal activity of vulgarone B against ram's horn snail (Planorbella trivolvis)

The ram's horn snail (Planorbella trivolvis (Say)) is an intermediate host for a digenetic trematode (Bolbophorus confusus (Krause) Dubois) that has recently been discovered to be a significant problem in commercial channel catfish (Ictalurus punctatus Raf) production ponds in the Mississippi Delta region in the USA. In these catfish ponds, the digenetic life cycle of this parasitic trematode involves two intermediate hosts, the ram's horn snail and the channel catfish, and the final host, the American white pelican (Pelecanus erythrorhynchos Gmelin). One approach to eradicate this problem is to disrupt the life cycle of the parasitic trematodes by eliminating the snails. During our search for natural-product-based molluscicides to control the snails in the catfish ponds, vulgarone B, isolated from the steam distillate of the aerial parts of the plant Artemisia douglasiana Besser (Asteraceae), was found to be active towards the snails with a LC50 of ca 24 microM. Channel catfish toxicity studies indicated a LC50 of ca 207 microM. Vulgarone B may be an environmentally acceptable alternative for snail control in aquaculture.     

Comparison of the type and number of microorganisms and concentration of endotoxin in the air of feedyards in the Southern High Plains

OBJECTIVES: To determine the bacterial, fungal, and endotoxin concentrations in aerosolized ambient air during the winter and summer in feedyards located in the Southern High Plains, identify aerosolized microbial pathogens, and determine the size of microbial and dust components. SAMPLE POPULATION: Aerosol samples were obtained from 7 feedyards. PROCEDURE: Aerosol samples were collected upwind, on-site, and downwind from each feedyard at a point 1 m above the ground by use of biological 2- and 6-stage cascade impactors. RESULTS: Significantly more microbes were cultured from on-site and downwind samples than upwind samples. There were significantly more microbes during the summer than during the winter. However, mean endotoxin concentration was significantly higher during the winter (8.37 ng/m3) than the summer (2.63 ng/m3). Among 7 feedyards, mean +/- SE number of mesophilic bacteria (1,441 +/- 195 colony-forming units [CFUs]/m3) was significantly higher than mean number of anaerobic bacteria (751 +/- 133 CFUs/m3) or thermophilic bacteria (54 +/- 10 CFUs/m3) in feedyard air. Feedyard aerosol samples contained more mesophilic fungi (78 +/- 7 CFUs/m3) than thermophilic fungi (2 +/- 0.2 CFUs/m3). Eighteen genera of bacteria were identified by use of an automated identification system. CONCLUSIONS AND CLINICAL RELEVANCE: It appeared that gram-negative enteric pathogens offered little risk to remote calves or humans via ambient aerosols and that gram-positive pathogens of the Bacillus, Corynebacterium, and Staphylococcus spp can be spread by aerosols in and around feedyards. It was common to detect concentrations of endotoxin in the ambient air of 7 feedyards.     

Relationship of bispectral index to minimum alveolar concentration multiples of sevoflurane in cats

OBJECTIVE: To determine the relationship between bispectral index (BIS) and minimum alveolar concentration (MAC) multiples of sevoflurane in cats. ANIMALS: 8 domestic cats. PROCEDURE: Each cat was anesthetized twice with sevoflurane. First, the MAC of sevoflurane for each cat was determined by use of the tail clamp method. Second, cats were anesthetized with sevoflurane at each of 5 MAC multiples administered in random order. Ventilation was controlled, and after a 15-minute equilibration period at each MAC multiple of sevoflurane, BIS data were collected for 5 minutes and the median value of BIS calculated. RESULTS: The mean (+/- SD) MAC of sevoflurane was 3.3 +/- 0.2%. The BIS values at 0.5 MAC could not be recorded as a result of spontaneous movement in all 8 cats. The BIS values at 2.0 MAC were confounded by burst suppression in all 8 cats. Over the range of 0.8 to 1.5 MAC, BIS values decreased significantly with increasing end-tidal sevoflurane concentrations. Mean (+/- SD) BIS measurements were 30 +/- 3, 21 +/- 3, and 5 +/- 2 at 0.8, 1.0, and 1.5 MAC, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Values of BIS are inversely and linearly related to end-tidal sevoflurane concentrations in anesthetized cats, and BIS may be a useful predictor of CNS depression in this species. The consistently low BIS values recorded in this study suggest that clinical BIS end points used to titrate anesthetic agents in humans may not be applicable to cats.     

Use of cisplatin, 5-fluorouracil, and second-look laparotomy for the management of gastrointestinal adenocarcinoma in three dogs

Three dogs with advanced-stage adenocarcinoma of the gastrointestinal tract were treated by use of resection, adjuvant chemotherapy with cisplatin and 5-fluorouracil, and second-look laparotomy (SLL). In combination with histologic examination of biopsy specimens obtained during the procedure, SLL is the most accurate diagnostic procedure for identification of residual or recurrent microscopic or macroscopic abdominal neoplasia; however, to the authors' knowledge, there are no reports of its clinical use in the field of veterinary oncology. This lack of clinical use in animals is likely because of factors such as cost, procedure-associated risks perceived by the owners and veterinarians, lack of data to define proper clinical application, and, perhaps to some degree, an entrenched belief that treatment of advanced stage cancer in animals is inappropriate. Nevertheless, the use of SLL should be considered for evaluation of abdominal tumors or intra-abdominal metastases in dogs that appear to be in complete clinical remission near or at the anticipated completion of chemotherapy (especially if effective second-line chemotherapy protocols are available) or when secondary cytoreduction might be beneficial.     

Massive hepatocellular carcinoma in dogs: 48 cases (1992-2002)

OBJECTIVE: To determine clinical signs, diagnostic findings, outcome, and prognostic factors in dogs treated surgically for massive hepatocellular carcinoma (HCC) and compare survival times of surgically and conservatively treated dogs. DESIGN: Retrospective study. ANIMALS: 48 dogs. PROCEDURE: Medical records were examined for clinical signs, diagnostic and surgical findings, and postoperative outcome. Dogs were allocated into surgery and nonsurgery groups depending on whether curative-intent liver lobectomy was performed. Data from the surgical and nonsurgical groups were analyzed to identify prognostic factors and determine and compare rates of tumor control and survival time. RESULTS: 42 dogs were treated surgically, and 6 were managed conservatively. In the surgery group, intraoperative mortality rate was 4.8% with no local recurrence, metastatic rate was 4.8%, and median survival time was > 1,460 days (range, 1 to 1,460 days). High alanine aminotransferase and aspartate aminotransferase activities were associated with poor prognosis. Median survival time for the nonsurgery group was 270 days (range, 0 to 415 days), which was significantly less than that of surgically treated dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Liver lobectomy is recommended for dogs with massive HCC because tumor-related mortality rate was 15.4 times higher in dogs in the nonsurgery group, compared with the surgery group. Tumor control was excellent after surgical resection with no local recurrence and a low metastatic rate. Prognostic factors were identified, but their clinical relevance was uncertain because only 9.5% of dogs in the surgery group died as a result of their disease.