Feline immunodeficiency virus status of Australian cats with lymphosarcoma

OBJECTIVE: To determine the FIV status of Australian cats with lymphosarcoma and relate this to patient characteristics, tumour characteristics (tissue involvement, histological grade and immunophenotype), haematological and serum biochemical values and FeLV status of affected cats. DESIGN: Prospective study of 101 client-owned cats with naturally-occurring lymphosarcoma. PROCEDURE: Western blot analysis, ELISA and immunochromatography were used to detect FIV antibodies in serum from cats with lymphosarcoma. RESULTS: On the basis of Western blot analysis (which was considered the most accurate method for determining FIV status), 50/101 (50%) of cats with naturally-occurring lymphosarcoma were positive for FIV antibodies. Of these 50 cats, 35 had tumours of B-cell phenotype, 13 had T-cell tumours and 2 had tumours classified as non-B/non-T. Tumours from eight of these FIV-positive cats contained FeLV gene sequences, including a 9-month-old cat with FeLV antigenaemia. Compared with FlV-negative cats with lymphosarcoma, FIV-positive cats were more likely to be domestic crossbreds (P = 0.004), male (P = 0.048) and have atypical (especially nasal) forms of lymphosarcoma (P = 0.09). Only 39 of 107 (36%) blood or sera tested using ELISA were positive for FIV antibodies (including 5 false-positives). CONCLUSIONS: The prevalence of FIV infection was considerably higher in our cohort of cats compared with series of lymphosarcoma cases from the Northern hemisphere. A positive FIV status was strongly associated with lymphosarcoma in Australian cats and it is possible that this infection may predispose to the development of lymphoid neoplasia. The presence of FIV infection would have been underestimated if commercial kits alone had been used for serology.     

Therapy for Australian cats with lymphosarcoma

OBJECTIVE: To determine the response of Australian cats with lymphosarcoma to chemotherapy and/or surgery in relation to patient and tumour characteristics, haematological and serum biochemical values and retroviral status. DESIGN: Prospective study of 61 client-owned cats with naturally-occurring lymphosarcoma subjected to multi-agent chemotherapy and/or surgery. PROCEDURE: An accepted chemotherapy protocol utilising l-asparaginase, vincristine, cyclophosphamide, doxorubicin, methotrexate and prednisolone was modified and used to treat 60 cats with lymphosarcoma. Clinical findings were recorded before and during therapy. As far as practical, cases were followed to death, euthanasia or apparent cure. Owner satisfaction with the results of chemotherapy was determined using a questionnaire sent after the completion of chemotherapy. RESULTS: One cat, with lymphosarcoma limited to a single mandibular lymph node, was treated using surgery alone and was cured. The other 60 cats were treated using multi-agent chemotherapy, although seven cats with localised intestinal, ocular and subcutaneous lesions had these lesions partially (2 intestinal lesions) or completely (2 eyes, 2 intestinal lesions and a cluster of regional lymph nodes) resected prior to starting chemotherapy. The median survival time for these 60 cats was 116 days. Of the 60 cats, 48 rapidly went into complete remission following the administration of 1-asparaginase, vincristine and prednisolone (complete remission rate 80%) and these cats had a median survival of 187 days. Three cats were censored from further analysis as their long-term survival data were uninterpretable because they died of causes unrelated to lymphosarcoma or were prematurely lost to follow-up. Twenty cats were classed as 'long-term survivors' based on survival time in excess of one year and at least 14 were 'cured' based on the absence of physical evidence of lymphosarcoma 2-years after initiating treatment. In other words, of the 48 cats that reached complete remission, in excess of 29% were 'cured'. Despite detailed analysis, few meaningful prognostic indicators based on patient or tumour characteristics were identified, although long-term survivors were more likely to be less than 4-years (P= 0.04) and to have tumours of the T-cell phenotype (P= 0.06). Excluding the one FeLV ELISA-positive cat with mediastinal LSA, 7 of 9 cats less than 4 years-of-age were long-term survivors (median survival time >1271 days). There was a strong association between achieving complete remission and long-term survival (P = 0.003). On the basis of 27 replies to a questionnaire, owners were generally very satisfied with the response to chemotherapy, irrespective of the survival time of the individual patient. Eighty five percent of owners expressed complete satisfaction with their decision to pursue chemotherapy and 70% believed their cat's health status improved during the first 2-weeks of treatment. Importantly, 78% of owners considered that chemotherapy required a very substantial time commitment on their part. CONCLUSIONS: It was possible to cure approximately one quarter of cats with lymphosarcoma using sequential multi-agent chemotherapy and/or surgery. FeLV-negative cats younger than 4 years (typically with mediastinal lymphosarcoma) had a particularly favourable prognosis. The decision to embark on chemotherapy should be based on the results of induction chemotherapy with l-asparaginase, vincristine and prednisolone, as the response to this was a good predictor of long-term survival. Cats surviving the first 16 weeks of chemotherapy generally enjoyed robust remissions (in excess of 1 year) or were cured of their malignancy.     

Feline leukaemia virus status of Australian cats with lymphosarcoma

OBJECTIVE: To determine the FeLV status of sera and tumours from Australian cats with lymphosarcoma in relation to patient characteristics, tumour characteristics (tissue involvement, histological grade and immunophenotype), haematological and biochemical values. DESIGN: Prospective study of 107 client-owned cats with naturally-occurring lymphosarcoma. PROCEDURE: An ELISA was used to detect FeLV p27 antigen in serum specimens collected from cats with lymphosarcoma. A PCR was used to detect FeLV DNA in formalin-fixed, paraffin-embedded tissue sections containing neoplastic lymphoid cells. The PCR was designed to amplify a highly conserved region of the untranslated long terminal repeat of FeLV provirus. RESULTS: Only 2 of 107 cats (2%), for which serum samples were available, were FeLV-positive on the basis of detectable p27 antigen in serum. In contrast, 25 of 97 tumours (26%) contained FeLV DNA. Of the 86 cats for which both PCR and ELISA data were available, 19(22%) had FeLV provirus in their tumours but no detectable circulating FeLV antigen in serum, while 2 (2%) had FeLV provirus and circulating FeLV antigen. FeLV PCR-positive/ELISA-negative cats (19) differed from PCR-negative/ELISA-negative cats (65) in having fewer B-cell tumours (P = 0.06), more non B-/non T-cell tumours (P = 0.02) and comprising fewer non-Siamese/Oriental pure-bred cats (P = 0.03). CONCLUSIONS: The prevalence of FeLV antigen or provirus was considerably lower in our cohort of cats compared with studies of lymphosarcoma conducted in the Northern hemisphere. This suggests that factors other than FeLV are important in the development of lymphosarcoma in many Australian cats. No firm conclusions could be drawn concerning whether FeLV provirus contributed to the development of lymphosarcoma in PCR-positive/ELISA-negative cats.     

Retrospective study of 60 cases of feline lymphosarcoma

Objective To characterise epidemiological and clinical findings, and diagnostic procedures undertaken, in cats with lymphosarcoma at a veterinary teaching hospital.
Design Retrospective case study.
Procedure Hospital records were reviewed for 7159 cats, sick or healthy, examined during a 10-year period (1984 to 1994). Sixty cats with lymphosarcoma were identified and classified by anatomical location of the tumour. Data on breed, age, sex, clinical signs and diagnostic procedures were collated.
Results The prevalence of feline lymphosarcoma in the hospital population was 0.84%. Siamese cats appeared predisposed to lymphosarcoma but other purebreds were not. Males were somewhat overrepresented amongst affected cats. Similar numbers of cases (12 to 18) were seen in each of the four anatomic categories (multicentric, mediastinal, alimentary and extranodal). Cats with mediastinal lymphosarcoma were mostly young and Siamese. Clinical signs in affected cats were varied, usually multiple and often nonspecific. Two of 22 cases tested positive for feline leukaemia virus antigen in blood and 6 of 13 were positive for feline immunodeficiency virus antibody.
Conclusions Extranodal lymphosarcoma seemed more prevalent in this study than reported elsewhere. Siamese cats in the study population may have had a genetic predisposition to lymphosarcoma. Limited evidence suggested feline leukaemia virus may be less important, and feline immunodeficiency virus more important, in the local population than indicated in overseas reports. Additional studies are needed to investigate breed predisposition and feline leukaemia virus and feline immunodeficiency virus status in Australian cats with lymphosarcoma.     

MRI features of CNS lymphoma in dogs and cats

The magnetic resonance (MR) imaging features of central nervous system lymphoma in eight dogs and four cats are described. Intracranial lesions affected the rostrotentorial structures in six dogs and caudotentorial structures in two cats. Lesions affected the spinal cord in two dogs and in two cats. One dog and one cat with intracranial lymphoma had signs of local extracranial extension and lymphadenopathy. Lesions were considered extraparenchymal in four dogs and three cats, intraparenchymal in two dogs and one cat, and appeared to have both intra- and extraparenchymal components in two dogs. All lesions were hyperintense in T2-weighted images when compared to white matter, most were hypointense in T1-weighted images (7/12), and most were hyperintense in fluid-attenuated inversion recovery (FLAIR) images (5/9). When compared to grey matter, these lesions appear either isointense (5/12) or hyperintense (7/12) on T2-weighted images, half of them were hypointense in T1-weighted images (6/12), and most were isointense in FLAIR images (7/9). Lesion margins were usually indistinct in T2-weighted images (10/12) and had perilesional hyperintensity in FLAIR images (7/9). The majority of lesions (10/12) had abnormal meninges around the lesion and half (6/12) had generalized contrast enhancement. Mass effect was evident in all lesions. Although not specific, when combined with the history and neurologic signs, MR features aid presumptive diagnosis that should be confirmed by cytology or histopathology.     

Chemotherapy with cyclophosphamide, vincristine, and prednisolone (COP) in cats with malignant lymphoma: new results with an old protocol

This retrospective study in 61 cats with malignant lymphomas examined the efficacy of a well-established chemotherapy protocol (cyclophosphamide, vincristine, and prednisolone [COP]) in the Netherlands, a country with a low prevalence of feline leukemia virus (FeLV). Twenty-two cats (36.1%) had mediastinal lymphoma, 11 (18.0%) had alimentary lymphoma, 7 (11.5%) had peripheral lymphoma, 8 (13.1%) had nasal lymphoma, and 13 (21.3%) had miscellaneous lymphoma (including renal lymphoma in 2 [3.3%]). Of the 54 cats that were tested, only 4 (7.4%) were FeLV positive. Complete remission (CR) was achieved in 46 of the 61 cats (75.4%). The estimated 1- and 2-year disease-free periods (DFPs) in the 46 cats with CR were 51.4 and 37.8%, respectively, whereas the median duration of remission was 251 days. The overall estimated 1-year survival rate in all cats was 48.7%, and the 2-year survival rate was 39.9%, with a median survival of 266 days. The median survival time and the 1-year survival rate for mediastinal lymphoma were 262 days and 49.4%. respectively. Siamese cats had a more favorable prognosis for survival and remission than other breeds. Response to therapy in this study was shown to be a significant prognostic indicator. CR is necessary for long-term survival. Cats that did not achieve CR had little chance of survival for longer than I year. Young Siamese cats in this study had a greater tendency to develop mediastinal malignant lymphoma at a young age, and all were FeLV negative. In comparison with results reported in other studies with different combination chemotherapy protocols, these are among the highest percentages of remission and the longest survival rates for cats with malignant lymphoma.     

Immunophenotypic and histological characterisation of 109 cases of feline lymphosarcoma

OBJECTIVE: To determine and analyse the immunophenotype and histological appearance of naturally occurring cases of lymphosarcoma in Australian cats. DESIGN: A prospective multi-institutional study of naturally occurring feline lymphosarcoma. METHODS: One hundred and eighteen cats were referred for diagnosis and/or management of suspected lymphosarcoma. Tissue samples for histopathological analysis and immunophenotyping were collected as biopsies or at necropsy from 109 cases. Histological classification of the neoplasms followed the Working Formulation Classification System. Four multi-species cross-reactive antibodies were used to classify tumours as having a B or T cell phenotype. RESULTS: Seventy-six (70%) cases were B cell tumours and 28 (26%) were T cell tumours. The remaining 5 (4%) specimens failed to stain with the four antibodies. Histologically, 11 (10%) cases were classified as low-grade, 72 (66%) were medium-grade and 26 (24%) were high-grade tumours. There were no significant associations between age and either histological grade or immunophenotype. Mediastinal and leukaemic cases were significantly more likely to be T cell tumours (P < 0.001 and P < 0.001, respectively). CONCLUSIONS: In contrast to previously documented studies in the cat, the majority of cases of lymphosarcoma were of B cell phenotype and intermediate histological grade. Based on our data, the histological phenotype of lymphosarcoma is unlikely to predict immunotype, nor are cases of certain immunotypes likely to be of specific histological subtype. Considered in relation to previous reports, the findings suggest that epidemiological factors operating in these cats to produce lymphosarcoma may be different to those operating in North American and UK cat populations.     

Pneumonia associated with Mycoplasma spp in three cats

Mycoplasma spp were isolated in pure culture from bronchoalveolar lavage specimens from three cats with clinical, cytological and radiographic signs of bron-chopneumonia or suppurative bronchitis. Predisposing factors were not identified in the first case, the second cat had oesophageal hypomotility, while the third cat had been exposed to cigarette smoke and had advanced periodontal disease. Respiratory signs resolved promptly and completely in all cases following antimicrobial therapy directed against mycoplasmas. Mycoplasma spp are possible causes of lower respiratory tract disease in cats and this should be considered when selecting empirical therapy for feline airway disease and pneumonia. In some situations mycoplasmas may behave as primary lower respiratory tract pathogens in cats.     

Serum cobalamin concentrations in healthy cats and cats with non-alimentary tract illness in Australia

Objective   To determine a reference range for serum cobalamin concentration in healthy cats in Australia using a chemiluminescent enzyme immunoassay and to prospectively investigate the prevalence of hypocobalaminaemia in cats with non-alimentary tract disease.
Design   Prospective study measuring serum cobalamin concentrations in clinically healthy cats and cats with non-alimentary tract illness.
Procedure   Blood was collected from 50 clinically healthy cats that were owned by staff and associates of Veterinary Specialist Services or were owned animals presented to Creek Road Cat Clinic for routine vaccination. Blood was collected from 47 cats with non-alimentary tract illness presented at either clinic. Serum cobalamin concentration was determined for each group using a chemiluminescent enzyme immunoassay.
Results   A reference range for Australian cats calculated using the central 95th percentile in the 50 clinically healthy cats was 345 to 3668 pg/mL. Median serum cobalamin concentration in 47 cats with non-alimentary tract illness (1186 pg/mL; range 117–3480) was not significantly different to the median serum cobalamin of the 50 healthy cats (1213 pg/mL, range 311–3688). Using the calculated reference range one sick cat with non-alimentary tract illness had a markedly low serum cobalamin concentration.
Conclusion   Although hypocobalaminaemia is uncommon in sick cats with non-alimentary tract illness in Australia, its occurrence in this study warrants further investigation.     

Susceptibility of cats to equine morbillivirus

Objective To assess the susceptibility of cats to equine morbillivirus (EMV) by direct administration of the virus by subcutaneous, intra-nasal or oral routes, and following exposure to infected cats.
Design A disease transmission study, with controls, using ten cats.
Procedure Groups of cats were given the virus by the designated methods and assessed for evidence of infection by clinical examination, plus pathological and virological tests.
Results All cats administered the virus by subcutaneous, intra-nasal or oral routes became infected and developed the disease within 4 to 8 days. One of two cats in contact with affected cats also developed the disease, but two cats kept near to affected cats did not become infected. The virus was isolated from a range of tissues collected from the infected cats, and the lesions observed in affected cats were similar to those previously observed in horses naturally and experimentally infected with the virus.
Conclusion This is the first demonstration that animals can be infected with EMV by non-parenteral means, that the virus can transmit naturally between animals and confirms other reports of the similarity of EMV disease in horses and cats.     

Snake envenomation in cats and its detection by rapid immunoassay

Objective To determine the usefulness of a snake venom detection kit (SVDK) in the management of envenomed cats.
Design A clinical study.  

Animals

Twenty-two cats were investigated.
Procedure Cats injected subcutaneously with approximately 0.25 or 1.0 lethal dose (LD) of tiger snake venom or 1 or 4 LD of brown snake venom were observed for clinical symptoms of envenomation at intervals over the ensuring 24 to 48 hours(h). Blood and urine samples were taken at regular intervals and assayed in a quantitative laboratory assay for snake venoms. Selected samples were assayed in parallel in a rapid, semi-quantitative SVDK.
Results The studies showed that it was important to estimate the elapsed time from envenomation to presentation. If this time was less than 8 h, blood was the most appropriate sample and a negative result should exclude serious envenomation. If the elapsed time exceeded 8 h, it was essential that urine be sampled. Venom levels in urine were high at 8 h and approached the level of test sensitivity over 24 to 48 h; however by this time clinical signs were obvious in endangered cats.  

Conclusions

Careful use of the SVDK is a valuable aid in the management of a potentially envenomed cat.     

Clinical and pathologic features of oligodendrogliomas in two cats

Two oligodendrogliomas in two domestic cats involved mainly the rostral brain stem, midbrain, fourth ventricle, and cerebellum. Both cats were aged neutered males presenting with clinical neurologic deficits suggestive of a brain stem lesion. Magnetic resonance imaging of both tumors demonstrated lesions with a pattern of heterogeneous contrast enhancement and multifocal lesions in one cat. Routine cerebrospinal fluid analysis was normal in one cat and suggestive of an inflammatory disease in the other. Oligodendroglioma cells were seen in cytospin preparations of cerebrospinal fluid from both cats. In each cat, the tumors occurred intraventricularly in the midbrain and fourth ventricle with aggressive intraparenchymal infiltration. There was extensive growth into the basilar subarachnoid space of the midbrain and brain stem in one cat. One tumor was well differentiated, and the other was an anaplastic subtype. Immunostaining for several myelin- and oligodendroglia-specific antigens was negative with formalin-fixed tumors and with unfixed frozen samples from one cat. In both tumors, component cells of the intratumoral vascular proliferations were positive for human von Willebrand factor VIII antigen or smooth muscle actin. Immunocytochemical reactivity for glial fibrillary acidic protein identified both reactive astrocytes and a subpopulation of minigemistocytes in both tumors. Ultrastructurally, the tumor cells were unremarkable except for their prominent desmosomal junctions and paucity of microtubules.     

Pharmacokinetics of vatinoxan in male neutered cats anesthetized with isoflurane

ObjectiveTo characterize the pharmacokinetics of vatinoxan in isoflurane-anesthetized cats.Study designProspective experimental study.AnimalsA group of six adult healthy male neutered cats.MethodsCats were anesthetized using isoflurane in oxygen. Venous catheters were placed to administer the drug and sample blood. Vatinoxan, 1 mg kg^–1, was administered intravenously over 5 minutes. Blood was sampled before and at various times during and up to 8 hours after vatinoxan administration. Plasma vatinoxan concentration was measured using liquid chromatography/tandem mass spectrometry. Compartment models were fitted to the time–concentration data using population methods and nonlinear mixed effect modeling.ResultsA three-compartment model best fitted the data. Typical value (% interindividual variability) for the three volumes (mL kg^–1), the metabolic clearance and two distribution clearances (mL minute^–1 kg^–1) were 34 (55), 151 (35), 306 (18), 2.3 (34), 42.6 (25) and 5.6 (0), respectively. Hypotension increased the second distribution clearance to 10.6.Conclusion and clinical relevanceThe pharmacokinetics of vatinoxan in anesthetized cats were characterized by a small volume of distribution and a low clearance. An intravenous bolus of 100 μg kg^–1 of vatinoxan followed by constant rate infusions of 55 μg kg^–1 minute^–1 for 20 minutes, then 22 μg kg^–1 minute^–1 for 60 minutes and finally 10 μg kg^–1 minute^–1 for the remainder of the infusion time is expected to maintain the plasma concentration within 90%–110% of the plasma vatinoxan concentration previously shown to attenuate the cardiovascular effects of dexmedetomidine (25 μg kg^–1) in conscious cats.     

Plasma fentanyl concentrations in awake cats and cats undergoing anesthesia and ovariohysterectomy using transdermal administration

Objective To measure the plasma fentanyl concentrations achieved over time with transdermal fentanyl patches in awake cats and cats undergoing anesthesia and ovariohysterectomy. Study design Randomized prospective experimental study. Animals Twenty‐four purpose‐bred cats. Methods Cats were randomly assigned to three groups for Part I of a larger concurrent study. Group P received only a 25 μg hour^?1 transdermal fentanyl patch. Group P/A received the patch and anesthesia. Group A received only anesthesia. After a minimum 1‐week washout period, the cats were randomly reassigned to two groups for Part II of the larger study. Group P/A/O received the patch, anesthesia and ovariohysterectomy. Group A/O received anesthesia and ovariohysterectomy. Patches were left in place for 72 hours and plasma samples were obtained for fentanyl analysis while the patches were in place, and for 8 hours after patch removal for cats in Group P, P/A, and P/A/O. Results The 25 μg hour^?1 transdermal fentanyl patches were well tolerated by the cats in this study (mean body weight of 3.0 kg) and no overt adverse effects were noted. Mean plasma fentanyl concentrations over time, mean plasma fentanyl concentrations at specific times (8, 25, 49, and 73 hours after patch placement), time to first detectable plasma fentanyl concentration, time to reach maximum plasma fentanyl concentration, maximum plasma fentanyl concentration, mean plasma fentanyl concentration from 8 to 73 hours, elimination half‐life, and total area under concentration (AUC) were not statistically different among the groups. Conclusions Halothane anesthesia and anesthesia/ovariohysterectomy did not significantly alter the plasma fentanyl concentrations achieved or pharmacokinetic parameters measured, when compared with awake cats. There was a high degree of individual variability observed both within and between groups of cats in parameters measured. Clinical significance The high degree of variability observed suggests that careful observation of cats with fentanyl patches in place is required to assess efficacy and any potential adverse effects. Anesthesia and anesthesia/ovariohysterectomy do not appear to alter plasma fentanyl concentrations achieved by placement of a 25 μg hour^?1 transdermal fentanyl patch when compared to cats not undergoing these procedures.     

Histologic features of hair follicle neoplasms and cysts in dogs and cats: a diagnostic guide

Hair follicle neoplasms occur in many different species, including humans. In domestic animals, they are most common in dogs. Most hair follicle tumors are benign, but malignant neoplasms can also occur. To diagnose hair follicle neoplasms, a thorough knowledge of follicular anatomy is important, given that follicular tumors are classified according to the differentiation pattern seen in the corresponding part of the normal hair follicle. This review focuses on the key diagnostic features of hair follicle tumors and follicular cysts in dogs and cats.