A randomised controlled comparison of aspiration and non-aspiration fine-needle techniques for obtaining ultrasound-guided cytological samples from canine livers.

Ultrasound-guided fine-needle sampling to obtain cytological samples is a well-established technique. However, the application of suction during sampling is controversial. Evidence from the human literature and one previous veterinary study suggest that non-aspiration may be superior for a number of organs. This prospective study compared the quality and diagnostic value of cytological samples from canine livers obtained by fine-needle aspiration (FNA) and non-aspiration (FN-NA) techniques. A total of 119 dogs that required ultrasound-guided FNA of the liver as part of their clinical investigation were recruited and randomly assigned to either FNA (n=54) or FN-NA (n=65) sampling groups. Specimens were reviewed by external cytopathologists masked to the technique used. Cytological reports were reviewed for their overall diagnostic value, cellularity, cell preservation and haemodilution. Overall, 88.2% (95% confidence intervals [CI], 82.4-94.0) of samples were diagnostic. There was a significant difference, as demonstrated by Chi-squared statistical analysis, in the prevalence of diagnostic samples between the FNA (81.5%; 95% CI, 71.1-91.8) and FN-NA groups (93.9%; 95% CI, 88.0-99.7; P=0.037). Non-diagnostic samples were significantly associated with lower cellularity, poorer cell preservation and more severe haemodilution (P<0.001 for each). However, there were no significant differences in the frequency of these specific variables between the FNA and FN-NA groups. In this study, fine-needle non-aspiration was superior to an aspiration technique for sampling the canine liver, as it resulted in higher rates of diagnostic cytology samples, with greater cellularity, less haemodilution and better cytological preservation.

Assessment of Lymphoid Molecular Clonality in Canine Thymoma.

The aim of this study was to document the molecular clonality of lymphoid cells in canine thymoma using polymerase chain reaction for antigen receptor rearrangement (PARR). Fifteen formalin-fixed and paraffin wax-embedded samples of canine thymoma were analyzed for T- and B-cell receptor clonality. Two of these 15 cases were excluded from the study due to insufficient DNA concentration. Twelve of the 13 remaining samples (92.3%) showed a polyclonal lymphoid component and in one case the lymphoid component was monoclonal (T-cell clonality). PARR could therefore be a useful tool for differentiating canine thymoma from canine mediastinal lymphoma.

Use of a rotary battery-powered device for the collection of bone marrow in dogs and cats.

Bone marrow biopsies form an important part of investigations into a large number of conditions in veterinary patients. In the human field, powered drivers specifically designed for the collection of bone marrow have become available. These systems have been shown to obtain better quality bone marrow, more quickly and with less pain. This study showed that a powered rotary bone marrow collection system could be used in dogs and cats to collect bone marrow, easily and without complications. Good quality bone marrow aspirates were obtained in the majority of patients; where aspirates could not be collected it was not possible to obtain aspirates from alternative sites using a standard manual technique. Bone marrow core samples were of increased size (mean useable area 16.5 mm(2)), compared to samples obtained using a standard manual technique (mean useable area 4.1 mm(2), P<0.001). Samples obtained using the powered system were also judged to be of significantly better diagnostic quality. The use of a powered system for bone marrow collection may aid the collection of better quality bone marrow samples in small animal patients.

Serum bromide concentrations following loading dose in epileptic dogs.

OBJECTIVE: To determine serum bromide concentrations following an oral loading dose in dogs. METHODS: Retrospective review of clinical records of dogs suffering from seizures that were treated with bromide. A loading dose of 600 mg/kg potassium bromide was administered orally in 17 to 48 hours together with a maintenance dose of 30 mg/kg/day. Blood samples were collected within 24 hours after completing the protocol and serum bromide concentrations were determined by ultra-violet gold chloride colorimetric assay. RESULTS: Thirty-eight dogs were included in the study. The median age was 3 (range, 0 · 2 to 10) years and bodyweight 21 · 8 (3 · 45 to 46 · 2) kg. The median serum bromide concentration was 1 · 26 (0 · 74 to 3 · 6) mg/mL. Thirty-two dogs (84 · 2%) had serum bromide concentrations within the therapeutic interval (1 to 3 mg/mL). The serum concentration in five dogs (13 · 2%) was just under the minimal therapeutic value and in one dog (2 · 6%) it exceeded the maximal therapeutic value (3 · 6 mg/mL). CLINICAL RELEVANCE: Following this oral loading dose protocol, serum bromide concentrations reach the therapeutic range in the majority of dogs. This indicates that the suggested protocol is effective in achieving therapeutic concentrations rapidly in epileptic dogs.

Genome Sequence of Streptococcus agalactiae Strain 09mas018883, Isolated from a Swedish Cow.

We announce the complete genome sequence of Streptococcus agalactiae strain 09mas018883, isolated from the milk of a cow with clinical mastitis. The availability of this genome may allow identification of candidate genes, leading to discovery of antigens that might form the basis for development of a vaccine as an alternative means of mastitis control.

STIR muscle hyperintensity in the cervical muscles associated with inflammatory spinal cord disease of unknown origin.

OBJECTIVES: To assess the relation of a distinctive pattern of short tau inversion recovery muscle hyperintensity with inflammatory cerebrospinal fluid result in dogs. METHODS: All dogs that had a short tau inversion recovery sequence performed in addition to other magnetic resonance sequences of the cervical spine and concurrent cerebrospinal fluid evaluation during the study period were included. All magnetic resonance studies were anonymised and reviewed by a board certified radiologist and board certified neurologist. A board certified pathologist examined the cerebrospinal fluid and the results were reviewed. RESULTS: Forty-nine cases fulfilled the inclusion criteria. Repeatable patterns of short tau inversion recovery hyperintensity were identified in 20 dogs. The clinical diagnosis in all these 20 cases was of meningoencephalomyelitis of unknown origin. This diagnosis was confirmed by inflammatory cerebrospinal fluid changes in 18 and suspected from clinical presentation and response to therapy in the remaining 2. CLINICAL SIGNIFICANCE: In this study, the short tau inversion recovery changes identified were restricted to cases with inflammatory spinal cord disease. The short tau inversion recovery change had a sensitivity of 78%, and a specificity of 92% in predicting inflammatory cerebrospinal fluid, suggesting that short tau inversion recovery sequences are a useful addition to the investigation of suspected inflammatory spinal cord disease.

Successful treatment of bilateral Paecilomyces pyelonephritis in a German shepherd dog.

A six-year-old female entire German shepherd dog was investigated for polyuria, polydipsia and lethargy. Investigations revealed a mild azotaemia and abdominal ultrasound revealed marked bilateral dilation of the renal pelves with echogenic material and proximal left hydroureter. Urine cytological examination and aspirates from the right renal pelvis revealed mats of fungal hyphae consistent with fungal bezoar formation. Fungal cultures revealed a profuse growth of Paecilomyces variotii. Initial treatment with oral itraconazole was unsuccessful, leading to bilateral nephrotomies to remove the fungal material. Postoperatively the Paecilomyces infection persisted despite continued itraconazole therapy. Treatment was commenced with amphotericin B, leading to resolution of the dog's clinical signs. To the authors' knowledge this is the first report of canine Paecilomyces pyelonephritis, without disseminated systemic disease, which documents its successful treatment.

Clinical pathological and epidemiological assessment of morphologically and immunologically confirmed canine leukaemia.

Traditionally, classification of leukaemia in dogs has relied on morphological examination and cytochemical staining patterns, but aberrant cellular morphology and stain uptake often curtails accurate categorization, and historical data based on this classification may be unreliable. Immunophenotyping is now the gold standard for classification of leukaemias. The purpose of this prospective study was to assess the clinical pathological and epidemiological features of a population of dogs with morphologically and immunologically confirmed leukaemia and to compare them within categories: acute and chronic lymphoid leukaemia (ALL and CLL), and acute and chronic myeloid leukaemia (AML and CML). There were 64 cases of morphologically and immunologically confirmed leukaemia: 25 cases of ALL, 17 cases of CLL and 22 cases of AML. Prevalence of B and T immunophenotypes in ALL and CLL was not statistically different. Dogs with AML were significantly younger than those with ALL at presentation (P = 0.04). Golden Retriever dogs in the study population were overrepresented in comparison with a control population of dogs (6/25 ALL cases, 8/64 leukaemia cases). No sex was overrepresented. Dogs with ALL had significantly more severe neutropenia (P = 0.001) and thrombocytopenia (P = 0.002) than those with CLL and had significantly more cytopenias. The severity and numbers of cytopenias seen in ALL and AML were not significantly different. Twenty-one of the leukaemia cases showed one cytopenia, fourteen had two cytopenias and twenty-one cases had pancytopenia. Anaemia was the most common cytopenia seen in isolation (17/21). No dogs had neutropenia without anaemia and/or thrombocytopenia. Total white blood cell counts were not different between the groups. The atypical cell counts within the peripheral blood were significantly higher in ALL than AML; both in isolation and as a percentage of the total white blood cell count (P = 0.03). This study strengthens the hypothesis that acute leukaemias give rise to more profound cytopenias, affecting more cell lines, than chronic leukaemias.

Intragenomic rearrangement in TT viruses: a possible role in the pathogenesis of disease.

A role for the ubiquitous Torque teno (TT) viruses in the pathogenesis of disease has not been resolved. In vivo and in vitro intragenomic rearrangement of TT virus genomes has been demonstrated. Replication in cell culture of a subviral molecule (411 bp) occurs through oligomerisation of RNA transcripts. Although the functions of the respective TT viral genes, as well as the newly formed genes in the rearranged subviral molecules, are largely unknown, certain similarities to genes of plant viruses of the family Geminiviridae will be described. A degree of similarity to certain cellular genes poses the question as to a role of molecular mimicry in the pathogenesis of autoimmune disease and diabetes.

TT viruses: oncogenic or tumor-suppressive properties?

Torque teno (TT) viruses have been more frequently reported in malignant biopsies when compared to normal control tissue. The possible contribution of TT virus infection to human carcinogenesis or the potential oncolytic functions of these virus infections are being discussed based on available experimental evidence. The data could suggest an involvement of TT virus infections as an indirect carcinogen by modulating T cell immune responses. Significant oncolytic functions, potentially mediated by the inhibition of nuclear factor (NF)-kappaB transcription factor or by apoptin-like gene activities, are emerging to be less likely.

Histopathologic, immunohistochemical, and cytologic analysis of feline myeloma-related disorders: further evidence for primary extramedullary development in the cat.

Feline myeloma-related disorders (MRD) are rare neoplasms of plasma cells. The multistep transformation model of myeloma in humans is based on the premise that plasma cells undergo neoplastic transformation primarily within the intramedullary compartment and that over time they become poorly differentiated and metastasize to extramedullary locations. Historically, diagnostic criteria used for human multiple myeloma have been applied to the cat, with the assumption that feline MRD commonly arises in the intramedullary compartment. Our objectives were to describe the features of feline MRD confirmed by cytology, histopathology, histochemistry, and immunohistochemistry and to categorize these tumors. A priori hypotheses were 1) tumor category predicts survival and 2) cats with well-differentiated tumors commonly have extramedullary involvement in contrast to human myeloma patients. This multicenter, retrospective study identified 26 MRD cases. There was good agreement between histopathologic and cytologic tumor categorization. Histochemistry and immunohistochemistry were shown to be valuable adjunct tests in the diagnosis of MRD. Cats with well-differentiated tumors had increased median survival relative to those with poorly differentiated tumors (254 versus 14 days). We have reported that marked extramedullary involvement at initial clinical presentation is significantly more common in the cat than in human MRD patients. In this study, we demonstrate that cats with well-differentiated tumors more commonly have extramedullary involvement than human myeloma patients with well-differentiated tumors (90% versus 20%, P < 0.0002). These results contrast strongly with the human myeloma model of primary intramedullary neoplastic transformation and suggest that primary extramedullary neoplastic transformation may be more common in feline MRD.

[Coincidental squamous cell cancers of the esophagus, head, and neck: risk and screening]. / "Field cancerization" im oberen Aerodigestivtrakt: Uberwachungsempfehlungen für Risikopersonen.

The term "field cancerization" was coined by Slaughter in1953 when describing multifocal synchronous and metachronous carcinogenesis in the upper aerodigestive system. Patients suffering from head and neck cancer (HNC) have or develop a second esophageal squamous cell cancer (ESCC) or bronchial cancer (BC) in 5-14% of cases. When a second esophageal cancer occurs in a patient with HNC, the prognosis is generally determined by the ESCC, and, unfortunately, it is poor. Screening and surveillance by Lugol chromoesophagoscopy enable early detection and curative treatment of second esophageal neoplasias. Surveillance appears to result in a survival benefit for HNC patients. Vice versa, patients with ESCC or BC have a risk of about 10% for developing HNC. Periodic pharyngolaryngoscopy is recommended for curatively treated ESCC or BC patients. Patients with field cancerization should be surveilled by a multidisciplinary approach.

[Coincidental squamous cell cancers of the esophagus and head and neck: risk and surveillance]. / Koinzidenz von Plattenepithelkarzinomen der Speiseröhre und Kopf-Hals-Karzinomen: Risiko und Früherkennung.

Patients suffering from head and neck cancer (HNC) have or will develop a second esophageal squamous cell cancer (ESCC) in 5 - 14 %. When a second esophageal neoplasm occurs in a HNC patient, the prognosis is generally determined by the ESCC, and unfortunately it is poor. Prospective clinical studies in Japan, Brazil, Taiwan, France and Germany have shown that screening or surveillance using Lugol chromoesophagoscopy enables early detection of second esophageal neoplasias. Such a surveillance results in a survival benefit for HNC patients. Vice versa, ESCC patients also have a risk of 9.3 - 11.4 % for a head and neck cancer. Periodic otolaryngeal examination and pharyngoscopy is recommended for curatively treated ESCC patients. Patients with a so-called field cancerisation of the airways and upper digestive tract thus require an interdisciplinary management and monitoring.

Histiocytic sarcoma of the spleen in flat-coated retrievers with regenerative anaemia and hypoproteinaemia.

Three flat-coated retrievers with a regenerative anaemia were examined. They were hypoproteinaemic suggesting that the anaemia might be due to blood loss, but it was not possible to identify a site of haemorrhage. All three had splenomegaly with splenic abnormalities apparent on ultrasonography. Ultimately all three animals were shown to have a histiocytic sarcoma involving the spleen and other tissues. A fourth flat-coated retriever with anaemia, hypoproteinaemia and an abdominal mass was also diagnosed with a histiocytic sarcoma of the spleen following splenectomy. It is postulated that the dogs' anaemia was due to erythrophagocytosis, either directly by neoplastic cells or by reactive macrophages.

Hypercalcaemia associated with granulomatous lymphadenitis and elevated 1,25 dihydroxyvitamin D concentration in a dog.

A seven-year-old Labrador was presented with weight loss and mild generalised lymphadenopathy. Histopathology of an excised lymph node by the referring veterinarian demonstrated granulomatous lymphadenitis. At the time of referral, fine-needle aspirates of the lymph nodes confirmed the presence of ongoing granulomatous inflammation. Further investigations revealed marked hypercalcaemia, a low parathyroid hormone concentration, a parathyroid hormone related protein concentration within the reference range, and an elevated serum concentration of 1,25 dihydroxyvitamin D. An underlying cause of the granulomatous lymphadenitis could not be identified. The clinical signs, hypercalcaemia and elevated serum concentrations of 1,25 dihydroxyvitamin D resolved following prednisolone treatment. In contrast to dogs, hypercalcaemia occurred secondarily to granulomatous disease and elevated 1,25 dihydroxyvitamin D concentrations is a well-recognised condition in human beings. To the authors' knowledge, this is the first case report to describe elevated serum calcium and 1,25 dihydroxyvitamin D concentrations in a dog with histologically confirmed granulomatous disease.

TAp63alpha indirectly regulates a cutaneous HPV promoter through complex formation with Jun family members.

The p63alpha isoforms of the p53 family have been demonstrated to play a crucial role in the development and differentiation of the skin. We show that expression of the TAp63alpha isoform leads to an upregulation of the cutaneous papillomavirus HPV 20 promoter, which is increased at least three-fold when c-Jun is co-expressed, in contrast to a minimal increase in activity in the presence of c-Jun alone. Co-expression of TAp63alpha with JunB or JunD, respectively, and in combination, leads to a reduction in the viral promoter activation measured by the expression of TAp63alpha alone. JunB and JunD also inhibits the additive effect exerted on the TAp63alpha activation by c-Jun. Co-immunoprecipitation assays demonstrate a complex formation of c-Jun, JunB and JunD with TAp63alpha through the SAM domain mediating protein-protein interactions, which is characteristic for p63alpha. Co-expression of p53 mutant R248W not only downregulates the differential modulation of the viral promoter by TAp63alpha alone and in the presence of the Jun family members, but leads to a reduction in the protein levels of the overexpressed c-Jun, JunB, JunD, as well as TAp63alpha. This model system provides insight into yet unknown pathways through which TAp63alpha and Jun may cooperate in the pathogenesis of HPV associated cutaneous lesions.

Intravenous cidofovir treatment for recalcitrant warts in the setting of a patient with myelodysplastic syndrome.

Cidofovir is an acyclic nucleoside phosphonate with broad-spectrum activity against DNA viruses, including human papilloma virus (HPV). However, data on the efficacy of cidofovir in an immunosuppressive setting remain contradictory. We report for the first time on the promotion of the healing of recalcitrant warts in a patient with myelodysplastic syndrome with intravenous cidofovir treatment.