Soft tissue sarcomas and mast cell tumours in dogs; clinical behaviour and response to surgery.

OBJECTIVE: To characterise the types of canine soft tissue sarcoma and mast cell tumour treated surgically at the University Veterinary Centre, Sydney. To evaluate the success of surgical treatment of these tumours and identify variables predictive of local recurrence and survival. To establish whether conclusions drawn from previous international studies are applicable to the University Veterinary Centre, Sydney, dog population and vice versa. DESIGN: Clinical presentation and results of surgical excision of 54 soft tissue sarcomas and 70 mast cell tumours affecting the trunk and limbs of dogs at the University Veterinary Centre, Sydney, between 1989 and 2001 were reviewed retrospectively. RESULTS: Cross-bred dogs and Rhodesian Ridgebacks were at significantly greater risk of developing soft tissue sarcomas, and Boxers, Australian Cattle Dogs and Staffordshire Bull Terriers were at significantly greater risk of developing mast cell tumours than other breeds. Fine needle aspiration biopsy yielded a correct diagnosis in 62.5% of soft tissue sarcomas and 96% of mast cell tumours. Local recurrence was encountered after surgical excision in 7.4% of soft tissue sarcomas and 7.3% of mast cell tumours. Metastasis occurred in 6% of soft tissue sarcomas and 12% of mast cell tumours. The most significant risk factors for local recurrence were contaminated surgical margins (soft tissue sarcomas) and histological grade (mast cell tumours). Due to the low number of animals experiencing metastasis, no conclusions could be drawn about significant risk factors. CONCLUSIONS: Aggressive surgical management of soft tissue sarcomas and mast cell tumours is associated with a low incidence of local recurrence. The type, location and behaviour of mast cell tumours and soft tissue sarcomas in the population of dogs presented to the University Veterinary Centre, Sydney are similar to those reported by others.

Spontaneous hepatic rupture in six cats with systemic amyloidosis.

Spontaneous hepatic rupture, secondary to the accumulation of hepatic amyloid, was diagnosed in six cats over a two-year period. Previous reports of feline hepatic amyloidosis have documented clusters of cases from breeding catteries. Most affected cats have been Siamese or a related breed and the disease is generally regarded as familial. In contrast, the cases presented here were sporadic, with relatives and other cats in the household not clinically affected. They included a Devon rex, a breed not previously reported with this condition, and a domestic shorthair. Clinical signs in three of these cases had, prior to referral, been misinterpreted as resulting from blunt trauma, immune-mediated haemolysis or a coagulopathy. Antemortem diagnostic features, including new data on the value of hepatic ultrasonography and fine-needle aspirate cytology, are reported. These cases illustrate how the course of this disease can vary between individuals and that, despite the dramatic underlying pathology, hepatic amyloidosis can present a diagnostic challenge and should be suspected in any young adult cat with consistent clinical signs, irrespective of breed or environment.

Cryptococcosis in ferrets: a diverse spectrum of clinical disease.

Cryptococcosis was diagnosed in seven ferrets (five from Australia; two from western Canada) displaying a wide range of clinical signs. Two of the ferrets lived together. One (5-years-old) had cryptococcal rhinitis and presented when the infection spread to the nasal bridge. Its sibling developed cryptococcal abscessation of the right retropharyngeal lymph node 12 months later, soon after developing a severe skin condition. DNA fingerprinting and microsatellite analysis demonstrated that the two strains isolated from these siblings were indistinguishable. Two ferrets (2- to 3-years-old) developed generalised cryptococcosis: one had primary lower respiratory tract disease with pneumonia, pleurisy and mediastinal lymph node involvement, while in the other a segment of intestine was the primary focus of infection with subsequent spread to mesenteric lymph nodes, liver and lung. The remaining three ferrets (1.75 to 4-years-old) had localised disease of a distal limb, in one case with spread to the regional lymph node. Cryptococcus bacillisporus (formerly C. neoformans var gattii) accounted for three of the four infections in Australian ferrets where the biotype could be determined. The Australian ferret with intestinal involvement and the two ferrets from Vancouver had C. neoformans var grubii infections.

Secreted lymphotoxin-alpha is essential for the control of an intracellular bacterial infection.

Although the essential role of tumor necrosis factor (TNF) in the control of intracellular bacterial infection is well established, it is uncertain whether the related cytokines lymphotoxin-alpha (LTalpha3) and lymphotoxin-beta (LTbeta) have independent roles in this process. Using C57Bl/6 mice in which the genes for these cytokines have been disrupted, we have examined the relative contribution of secreted LTalpha3 and membrane-bound LTbeta in the host response to aerosol Mycobacterium tuberculosis infection. To overcome the lack of peripheral lymph nodes in LTalpha-/- and LTbeta-/- mice, bone marrow chimeric mice were constructed. LT-/- chimeras, which lack both secreted LTalpha3 and membrane-bound LTbeta (LT1beta2 and LT2beta1), were highly susceptible and succumbed 5 wk after infection. LTbeta-/- chimeras, which lack only the membrane-bound LTbeta, controlled the infection in a comparable manner to wild-type (WT) chimeric mice. T cell responses to mycobacterial antigens and macrophage responses in LTalpha-/- chimeras were equivalent to those of WT chimeras, but in LTalpha-/- chimeras, granuloma formation was abnormal. LTalpha-/- chimeras recruited normal numbers of T cells into their lungs, but the lymphocytes were restricted to perivascular and peribronchial areas and were not colocated with macrophages in granulomas. Therefore, LTalpha3is essential for the control of pulmonary tuberculosis, and its critical role lies not in the activation of T cells and macrophages per se but in the local organization of the granulomatous response.

Impaired thrombin generation in beta 2-glycoprotein I null mice.

Autoimmune antibodies to beta(2)-glycoprotein I (beta2GPI) have been proposed to be clinically relevant because of their strong association with thrombosis, miscarriage, and thrombocytopenia. By using a homologous recombination approach, beta2GPI-null mice were generated to begin to understand the physiologic and pathologic role of this prominent plasma protein in mammals. When beta2GPI heterozygotes on a 129/Sv/C57BL/6 mixed genetic background were intercrossed, only 8.9% of the resulting 336 offspring possessed both disrupted alleles. These data suggest that beta2GPI plays a beneficial role in implantation and/or fetal development in at least some mouse strains. Although those beta2GPI-null mice that were born appeared to be relatively normal anatomically and histologically, subsequent analysis revealed that they possessed an impaired in vitro ability to generate thrombin relative to wild type mice. Thus, beta2GPI also appears to play an important role in thrombin-mediated coagulation.

An outbreak of pulmonary mycosis in respiratory burst-deficient (gp91(phox-/-))Mice with concurrent acidophilic macrophage pneumonia.

An outbreak of pulmonary abscessation due to the common environmental fungus Paecilomyces variotii occurred in a colony of gp91(phox-/-)mice, which lack functional NADPH oxidase, the enzyme complex responsible for generating the respiratory burst in phagocytes. Parenchyma surrounding the abscesses showed intense acidophilic macrophage pneumonia, and similar but much milder lesions were present in each of 24 gp91(phox-/-)mice free from other pulmonary lesions. These findings indicate a high prevalence of acidophilic macrophage pneumonia in gp91(phox-/-)mice, or at least in this particular stock. The presence of this lesion may complicate studies in which phagocyte-dependent pulmonary defence plays a significant role.

Feline inductive odontogenic tumour in a Burmese cat.

A 7-month-old, male, Burmese cat was presented with an oral mass that had rapidly regrown following excisional biopsy 3 weeks earlier. The tumour was identified by histological examination as a feline inductive odontogenic tumour. A unilateral segmental mandibulectomy was performed. Although dental malocclusion resulted from mandibular drift to the operated side, the cat displayed minimal dysphagia post-operatively and there was no evidence of tumour regrowth 8 months after surgery. Feline inductive odontogenic tumour is a rare dental tumour described exclusively in cats under 3-years-of-age. Although histopathologically benign, feline inductive odontogenic tumour grows by expansion and can infiltrate underlying bone to cause considerable local destruction. This article is intended to increase awareness of this unusual tumour which, with complete surgical excision, carries a good prognosis. It also emphasises the importance of obtaining a histological diagnosis from oral mass lesions to direct appropriate therapy and to provide an accurate prognosis.

Branchial cysts in laboratory mice.

Large solitary cysts in the superficial tissues of the ventral neck are described in five laboratory mice of two inbred strains and one outbred line. The cysts were lined by cuboidal to columnar epithelium similar to that in branchial cysts reported in other animal species but distinct from the stratified squamous epithelium with prominent lymphoid tissue typical of branchial cysts in man. These findings suggest that the lesion referred to as a branchial cyst in animals differs slightly from the lesion of the same name in man.

Interferon-gamma plays a critical role in intestinal immunity against Salmonella typhimurium infection.

Salmonella bacteria are a major cause of food-borne infectious diarrhoea and there is great interest in understanding the pathogenesis of Salmonella infection and in vaccine development. Potential vaccines include the aromatic mutants of S. typhimurium. Such non-lethal Aro mutants have also been useful for studying Salmonella infections in mouse models. Studies of systemic infection, using these Aro mutants, in both normal and cytokine gene knockout mice, indicate that interferon-gamma (IFN-gamma) plays a key role in the resolution of Salmonella infection. The present studies have investigated the outcome of oral infection in mice with attenuated Salmonella because this infection route mimics natural infection in humans. In IFN-gamma gene knockout (IFN-gamma-/-) mice, intestinal immunity was impaired and oral challenge resulted in disseminated septicaemia 2 weeks later. No dissemination of infection was seen in wild-type mice. In wild-type mice, both CD4 and CD8 cell numbers increased in the gut following Salmonella challenge, together with increased expression of major histocompatibility complex (MHC) II and vascular cell adhesion molecule-1 (VCAM-1). No such changes were seen in IFNgamma-/- mice. Following oral challenge, antilipopolysaccharide (LPS) and antiphosphoryl choline antibodies increased by more than 100-fold in both serum and faecal pellet extracts of IFNgamma-/- mice compared with wild-type mice. Our data show that IFN-gamma production is essential for resolution of enteric Salmonella infection and that antibody has little effect on this process.

Surgical removal of an ependymoma from the third ventricle of a cat.

A 10-year-old spayed domestic shorthaired cat was presented for behavioural changes, signs suggestive of visual deficits and aimless circling. Neuro-ophthalmological examination suggested the cat had central blindness. CT scans following administration of iohexol demonstrated a contrast-enhancing mass in the vicinity of the third ventricle resulting in obstructive hydrocephalus. Following rostral tentorial craniotomy and incision through the cerebral cortex, the third ventricle was approached via the dilated left lateral ventricle. An ependymoma was seen through a dorsocaudolateral incision into the third ventricle, and removed by gentle manipulation and suction. The cat recovered unremarkably, regaining normal vision and behaviour.

Granulomatous peritonitis and pleuritis in interferon-gamma gene knockout mice naturally infected with mouse hepatitis virus.

OBJECTIVE: To investigate a disease outbreak in a colony of laboratory mice with targeted disruption of the gene for interferon-gamma. FORMAT: A case report based on necropsy, histopathology, serology and immunohistochemistry. RESULTS: Affected mice exhibited depression and variable ascites. Necropsy revealed a granulomatous peritonitis and pleuritis with extensive adhesions although parenchymal lesions were minimal. Serum samples had high concentrations of antibody to mouse hepatitis virus and immunohistochemical examination revealed the presence of mouse hepatitis virus antigen in granuloma macrophages. Sero-logical testing for other infectious agents and bacterial culture were negative and wild type mice kept in the same facility remained healthy. Despite the association between the disease and mouse hepatitis virus infection, the precise role played by mouse hepatitis virus was not determined. While the disease is superficially similar to feline infectious peritonitis (another coronavirus-induced serositis), differences exist between the histopathological findings in these two conditions. CONCLUSION: This unusual disease process illustrates how new diagnostic challenges can arise in novel mouse genotypes created through molecular genetics. Furthermore, the association between the disease and mouse hepatitis virus illustrates the importance of maintaining laboratory animals under specific-pathogen free conditions.

Structural deficiencies in granuloma formation in TNF gene-targeted mice underlie the heightened susceptibility to aerosol Mycobacterium tuberculosis infection, which is not compensated for by lymphotoxin.

TNF and lymphotoxin-alpha (LT alpha) may act at various stages of the host response to Mycobacterium tuberculosis. To dissect the effects of TNF independent of LT alpha, we have used C57BL/6 mice with a disruption of the TNF gene alone (TNF-/-). Twenty-one days following aerosol M. tuberculosis infection there was a marked increase in the number of organisms in the lungs of TNF-/- mice, and by 28-35 days all animals had succumbed, with widespread dissemination of M. tuberculosis. In comparison with the localized granulomas containing activated macrophages and T cells in lungs and livers of C57BL/6 wild-type (wt) mice, cellular infiltrates in TNF-/- mice were poorly formed, with extensive regions of necrosis and neutrophilic infiltration of the alveoli. Phenotypic analysis of lung homogenates demonstrated similar numbers of CD4+ and CD8+ T cells in TNF-/- and wt mice, but in TNF-deficient mice the lymphocytes were restricted to perivascular and peribronchial areas rather than colocated with macrophages in granulomas. T cells from TNF-/- mice retained proliferative and cytokine responses to purified protein derivative, and delayed-type hypersensitivity to purified protein derivative was demonstrable. Macrophages within the lungs of TNF-/- and wt mice showed similar levels of MHC class II and inducible nitric oxide synthase expression, and levels of serum nitrite were comparable. Thus, the enhanced susceptibility of TNF-/- is not compensated for by the presence of LT alpha, and the critical role of TNF is not in the activation of T cells and macrophages but in the local organization of granulomas.

Quantitative and qualitative changes in intestinal goblet cells during primary infection of Trichostrongylus colubriformis high and low responder guinea pigs.

Small intestine goblet cell numbers and the composition of their mucus were compared in guinea pigs with genetically determined differences in responsiveness to Trichostrongylus colubriformis infection. Prior to infection, no differences between high responder and low responder animals were detected. However, following primary infection with T. colubriformis, pronounced goblet cell hyperplasia developed and the proportion of sulphomucin in these cells increased. Both changes developed significantly earlier in high responder animals.

Use of polymerase chain reaction to diagnose a natural outbreak of mouse hepatitis virus infection in nude mice.

The enormous cost of eliminating mouse hepatitis virus (MHV) from a mouse colony demands that a confirmed etiologic diagnosis be made to justify the necessary remedial action. We describe an outbreak of MHV in nude mice in which histopathologic findings provided a presumptive diagnosis, but results of serologic testing of affected nude mice and immunocompetent sentinels were negative. Results of transmission electron microscopy of liver specimens from affected mice were equivocal. Confirmation of the etiopathogenesis was eventually provided by reverse transcriptase-polymerase chain reaction (RT-PCR), using primers with nested sequences directed to two separate but highly conserved regions of the MHV genome. This procedure detected MHV in the liver of an affected nude mouse and in a sentinel, although in the latter a positive result was obtained only because of the increased sensitivity of nested primers used in a second round of amplification. Virus was not detected in cell lines that had been injected into the mice, and the source of the outbreak was not found. These results indicate the applicability of RT-PCR for detecting MHV in a field situation while also illustrating that conventional, complementary techniques still have an essential role in reaching a diagnosis. It is recommended that specimens should be taken for histologic examination and serologic testing, as well as for molecular studies when MHV infection is suspected.

Optimizing arthroscopic knots.

Arthroscopic repairs, such as those for shoulder instability, are commonly performed. However, the failure rate after arthroscopic repair appears to be higher than with open surgery. These failures may relate to the challenge of tying secure knots arthroscopically. Many knots tied arthroscopically commonly consist of an initial slip knot to remove slack, and a series of half-hitches. Half-hitches, instead of square throws, are difficult to avoid and result when asymmetrical tension is applied to the strands. For this reason, the security of knots tied arthroscopically may not be equivalent to square knots and a greater rate of failure may occur. The purpose of this study was to determine (1) the security of various arthroscopic knots under cyclic and peak loading conditions, (2) how the surgeon can modify the method or sequence of half-hitch throws to minimize knot slippage or breakage, and (3) whether using an arthroscopic knot pusher affects the security of the same knot tied by hand. The most secure knot configurations were achieved by reversing the half-hitch throws and alternating the posts. These knots performed significantly better than all other knots tested (P < .002). Thus the surgeon can control the holding capacity and minimize suture loop displacement by proper alternation of the tying strands and reversal of the loop when placing the hitches.(ABSTRACT TRUNCATED AT 250 WORDS)

Basophil leucocytes in responses to parasitic infection and some other stimuli in sheep.

Basophil leucocytes are a significant component of the infiltrating cells in a variety of tissue reactions in guinea pigs. However, little is known about the participation of basophils in similar reactions in most other animal species. The circulating blood, skin and small intestinal mucosa of sheep were examined after they had received stimuli known to elicit basophil-rich responses in guinea pigs but relatively few basophils were found.

Chronic intestinal pseudo-obstruction in a dog.

A three-year-old neutered female Border Collie was presented with inappetence, vomiting and diarrhoea. Abdominal radiographs revealed an obstructive pattern but no physical obstruction was evident at laparotomy. A diagnosis of chronic intestinal pseudo-obstruction was made based on histopathological changes in intestinal biopsies. Treatment was unsuccessful and the dog deteriorated progressively until euthanased five weeks after presentation.