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Acinic cell carcinoma is a rare, typically indolent, neoplasm that arises in the salivary glands. Metastatic disease is uncommon, occurring in around 10% of cases. We report the case of a 46-year-old male in whom the first sign of disseminated disease was increased skin pigmentation due to paraneoplastic Cushing’s syndrome. He underwent 3 cycles of chemotherapy with carboplatin and paclitaxel with no symptomatic improvement and a mixed response on imaging. There is no evidence that systemic therapy prolongs survival in metastatic acinic cell carcinoma, and we lack a consensus as to which treatment options are most beneficial. A summary of published evidence regarding choice of palliative chemotherapy regimens and response is discussed in relation to the case.

The outbreaks of foot-and-mouth disease (FMD) in Europe in 2001 identified the vulnerability of the intensive agricultural industries in Europe and North America to the economic consequences of the introduction of a highly infectious animal disease. The very large illegal international trade in animal products bypasses the safeguards recommended by World Animal Health Organization (OIE) and put in place by governments to prevent the importation of foreign pathogens. If it is not possible to stop the entry of FMD virus, what are the options to mitigate the risk by reducing the area of the globe in which FMD is endemic? There are a number of constraints that would prevent global control of FMD; current vaccines are expensive, have a narrow antigenic spectrum, provide only short term immunity and are very fragile; diagnostics are also expensive, require training to use and if not handled properly lose sensitivity and specificity; we still do not understand the significance of carrier animals in the epidemiology of FMD, and whether it is necessary or possible to prevent the carrier state; and many decision support tools, such as models are currently more dangerous than useful in that they fail to fully accommodate all the complexities of the disease. The four national foreign animal disease laboratories in USA, Canada, UK and Australia together with the International Livestock Research Institute have put forward a proposal to address some of these constraints (the Global FMD Research Alliance, GFRA), not only to protect their own national livestock industries, but also to support FMD control programs in countries in which the disease is present.

The foot-and-mouth disease virus (FMDV) is a member of the picornavirus family, possessing an 8-kb single-stranded RNA genome of positive polarity. It is highly contagious among several livestock species and can lead to severe economic consequences, as evidenced by the UK outbreak in 2001. The usage of real-time polymerase chain reaction has facilitated rapid detection of FMDV. Several real-time PCR instruments are available with various capabilities, such as portability and high sample volume analysis. Primers and a dual-labeled TaqMan probe were optimized to detect a single, highly conserved 88-bp segment of the FMDV 3D (RNA polymerase) gene. To increase the confidence of the RT-PCR result, a positive amplification control was synthesized to detect potential false-positive results due to contamination if a wildtype virus is used as positive control. In addition, a preventative measure against false-negative results was developed in which endogenous beta actin mRNA is coamplified by RT-PCR. Assay performance was compared on the LightCycler1.2 (Roche), the SmartCyclerII (Cepheid), and the SDS 7900HT (ABI). These assays successfully identified the FMDV genome and beta actin mRNA from several sources of infected nasal and oral swabs, as well as probang samples.

The 2001 epidemic of foot-and-mouth disease in the United Kingdom triggered a livestock culling campaign that involved the slaughter of more than 6.5 million animals. Three years later, management of the epidemic remains controversial. Some believe that untried control methods based on unvalidated models replaced well-established policy, motivating an unnecessary slaughter. Others hold that rigorous quantitative approaches provided the basis for new incisive policies that significantly curtailed the epidemic. Now, new and more flexible control policies have been adopted throughout Europe. For these policies to receive the full confidence of scientists, veterinarians and the general public, it is necessary that we improve both our understanding of where, how and why control measures initially failed in 2001 and how new policies should be implemented.

There is a global need to elucidate protective antigens expressed by the SARS-coronavirus (SARS-CoV). Monoclonal antibody reagents that recognise specific antigens on SARS-CoV are needed urgently. In this report, the development and immunochemical characterisation of a panel of murine monoclonal antibodies (mAbs) against the SARS-CoV is presented, based upon their specificity, binding requirements, and biological activity. Initial screening by ELISA, using highly purified virus as the coating antigen, resulted in the selection of 103 mAbs to the SARS virus. Subsequent screening steps reduced this panel to seventeen IgG mAbs. A single mAb, F26G15, is specific for the nucleoprotein as seen in Western immunoblot while five other mAbs react with the Spike protein. Two of these Spike-specific mAbs demonstrate the ability to neutralise SARS-CoV in vitro while another four Western immunoblot-negative mAbs also neutralise the virus. The utility of these mAbs for diagnostic development is demonstrated. Antibody from convalescent SARS patients, but not normal human serum, is also shown to specifically compete off binding of mAbs to whole SARS-CoV. These studies highlight the importance of using standardised assays and reagents. These mAbs will be useful for the development of diagnostic tests, studies of SARS-CoV pathogenesis and vaccine development.

An outbreak of severe acute respiratory syndrome (SARS) in humans, associated with a new coronavirus, was reported in Southeast Asia, Europe, and North America in early 2003. To address speculations that the virus originated in domesticated animals, or that domestic species were susceptible to the virus, we inoculated 6-week-old pigs and chickens intravenously, intranasally, ocularly, and orally with 106 PFU of SARS-associated coronavirus (SARS-CoV). Clinical signs did not develop in any animal, nor were gross pathologic changes evident on postmortem examinations. Attempts at virus isolation were unsuccessful; however, viral RNA was detected by reverse transcriptase-polymerase chain reaction in blood of both species during the first week after inoculation, and in chicken organs at 2 weeks after inoculation. Virus-neutralizing antibodies developed in the pigs. Our results indicate that these animals do not play a role as amplifying hosts for SARS-CoV.

Foot-and-mouth disease (FMD) is the most contagious disease of animals and a major constraint to international trade in live- stock and animal products. Clinical signs are characterized by vesicular lesions in and around the mouth, on the feet, and on the teats of dairy cattle. In adult sheep and goats, however, infection is frequently subclinical, or only mild lesions may appear. Rapid diagnosis of FMD is of great importance in the prevention and control of the disease. FMD is initially diagnosed clinically and confirmed by laboratory tests. However, testing for antibodies to FMD virus is also important for screening animals before move- ment, for vaccine potency testing, and for epidemiological studies. Nucleic acid detection techniques are powerful tools for rapid and sensitive diagnosis of the disease, with results comparable to those obtained by virus isolation. Considerable effort and atten- tion is now being directed toward the development of new methods and techniques for the rapid and accurate diagnosis of FMD, as well as the production of defined reagents.

If an infectious agent is to maintain itself within a closed population by means of an unbroken serial chain of infections, it must maintain the level of infectiousness of individuals through time, or termination of the transmission chain is inevitable. One possible cause of diminution in infectiousness along serial chains of transmission may be that individuals are unable to amplify and transmit comparable levels of the infectious agent. Here, the results are reported of a novel experiment designed specifically to assess the effects of serial passage of foot-and-mouth disease virus (FMDV) in experimental groups of sheep. A virus isolate taken from an epidemic of foot-and-mouth disease (FMD) characterized by rapid fade-out of infection was passed serially through four groups of sheep housed in an isolation unit. Although it was not possible to measure individual infectiousness directly, blood virus load from infected individuals was quantified using a real-time PCR assay and used as an underlying indicator of the level of infection. The results of this assay concurred well with those of the traditional tissue-culture assay and were shown to be highly repeatable. The level of peak viraemia was shown to fall significantly with the time of infection and with passage group, both in terms of the group mean and regression analysis of individual values, suggesting that this isolate of FMDV may, under certain conditions, be unable to maintain itself indefinitely in susceptible sheep populations. The results of these experiments are discussed in terms of the epidemiology of FMD in sheep.

Nucleotide sequence of the structural protein-encoding region of foot-and-mouth disease virus (FMDV) A22-India 17/77 was determined using non-radioisotopic technique. Comparison of nucleotide and deduced amino acid sequence with A22-Iraq 24/64 revealed 175 synonymous (silent) and 42 non-synonymous nucleotide changes resulting in 34 amino acid substitutions along the capsid proteins (VP1–VP4). Out of the 4 structural proteins VP4 is highly conserved. The highly variable and immunodominant protein VP1 showed 47% of the total amino acid substitutions. VP2 and VP3 contain 38.2% and 14.7% of the amino acid substitutions, respectively. The VP1-based phylogenetic analysis of 18 different type A viruses including A22-India 17/77 divided them in to two broad genetic groups (Asian and European/South American), and each group is further subdivided in to two separate genotypes. A22-India 17/77, A22-Iraq 24/64 and A22-Azerbaijan/65 formed one genotype and the 4 Chinese strains formed a separate genotype in the Asian group of viruses. In the European/ South American group, A-Argentina/87 represents one genotype and the remaining 10 strains formed the second genotype in this group.

Background: Endoscopy is increasingly used in paediatric practice for diagnosis of enteropathy, although the quality of grasp forceps-obtained biopsy specimens required for reliable diagnosis has been questioned in comparison with suction capsule biopsy specimens. This study prospectively compared the diagnostic suitability of grasp forceps biopsy versus suction biopsy in the same patient during the same procedure. Methods: A double-port paediatric suction biopsy capsule was front-loaded onto an endoscope and directed to the fourth part duodenum-proximal jejunum for biopsy sampling. Subsequently, three grasp biopsy specimens were taken from the same region. All biopsies were coded, photographed, and measured for area, using computed morphometry. A single blinded histopathologist assessed sample adequacy for diagnosis. Twenty-nine patients were enrolled (age range, 8-185 months). Results: On three occasions the suction capsule failed to fire, and on four occasions only one sample was obtained. Three grasp biopsy specimens were obtained on each occasion by endoscopy, and the first two were used for comparison with suction biopsy samples. Median total area of individual biopsy samples obtained by the two procedures was not different (21.3 vs. 22.5 mm 2 ; P = 0.027). Muscularis mucosae was obtained more commonly with grasp biopsies (P < 0.001), and no difference was observed for the presence of three or more villus-crypt units, degree of haemorrhage, or optimal orientation. Two suction biopsy procedures and one grasp biopsy procedure were inadequate for diagnosis. Conclusions: Endoscopic grasp biopsies are perfectly adequate for the assessment of small intestinal histology. In addition, endoscopy affords advantage in diagnosis of other upper gastrointestinal disease with avoidance of radiologic screening involved with the suction capsule technique.

THE establishment of the Single Market in the European Union and freer movement of animals and products has increased the risk that some diseases that have been eliminated from the United Kingdom could return, almost without notice. This article describes the important epidemiological and diagnostic features of the viral and subviral diseases of cattle, sheep and goats that are notifiable in the UK. An article on the notifiable diseases of pigs has been published previously in In Practice (May 1994, pp 110-128).

An ovine testis cell line (OA3.Ts) was evaluated and compared with primary lamb kidney (LK) cells for its utility in capripoxvirus propagation and titration. A comparison of OA3.Ts cell growth kinetics and morphology at low (

Foot-and-mouth disease (FMD) is a highly contagious and economically significant disease of cattle, pigs, sheep, goats and wild ruminant species. The FMD virus genome encodes a unique polyprotein from which the different viral polypeptides are cleaved by viral proteases, including eight different non-structural proteins (NSPs). Both structural and non-structural antigens induce the production of antibodies in infected animals. In contrast, vaccinated animals which have not been exposed to replicating virus will develop antibodies only to the viral antigens in the inactivated material. Vaccination against FMD is a key element in the control of the disease in addition to slaughter and movement restrictions. However, countries that vaccinate in the event of an outbreak will have to re-establish their FMD free status to the satisfaction of their trading partners. Because currently available vaccines stimulate the production of antibodies indistinguishable from those produced by infected animals in response to live virus and because vaccinated animals can be infected and become carriers of FMD virus, efforts have been made to develop diagnostic test that can differentiate vaccinated animals from those that are convalescent and from those that have been vaccinated and become carriers following subsequent contact with live virus. Currently the detection of antibodies to non-structural protein's (NSPs) is the preferred diagnostic method to distinguish virus infected, carrier, animals from vaccinated animals. However this is currently only possible at the herd level because of the great variability in the initiation, specificity and duration of the immune response in individual animals to the NSPs shown in many studies. Considerable effort and attention is now being directed toward the development of new methods and techniques for the rapid and accurate detection of anti-NSP antibodies, harmonization and standardization of current diagnostic techniques, as well as the production of defined reagents.

WE refer to the recent paper in Science by Charleston and others (2011) on the relationship between clinical signs and transmission for an infection with foot-and-mouth disease virus (FMDV) and to the News report of this paper in Veterinary Record (May 14, 2011, vol 168, p 498). The results presented are interesting, and provide welcome support for conclusions derived from careful analysis of the field data from the 2001 epidemic of FMD in the UK (mentioned below), but we feel that they are not the breakthrough seemingly implied in the paper and the media reaction to it. We consider that the results must be interpreted with caution and that the conclusions to be drawn are more limited than suggested. First, the paper reports results using a single strain of FMDV (the strain responsible for the UK outbreak of 2001) to infect only one species of animal (cattle). However, and very importantly, it is well known that FMDV varies significantly between its many strains and …

To identify the genetic determinants of virulence for swine vesicular disease virus, a panel of recombinant and site-directed mutant viruses were constructed from cDNA clones of a virulent J1'73 strain and an avirulent H/3'76 strain. Initial studies mapped the genetic determinants of virulence to either or both of the two sites at nucleotide (nt) 2842, encoding VP1-132, and nt 3355, encoding 2A-20. To determine their relative importance with regard to virulence, viruses mutated at either of these two sites from the avirulent to the virulent genotype and vice versa were tested in pigs. Viruses, mutated at nt 2842 to the virulent genotype (vSVLS104MJ1) or mutated at nt 3355 to the virulent genotype (vSVLS201MJ1), slightly recovered virulence but were very weak compared with viruses with site-directed mutations at both sites (vSVLS104/201MJ1). On the other hand, viruses, mutated at nt 2842 to the avirulent genotype (vSVLS104M00) or mutated at nt 3355 to the avirulent genotype (vSVLS201M00), did not have attenuated virulence. Sequence analysis of viruses recovered from inoculated pigs revealed that reversion at nt 3355 to the virulent genotype occurred in pigs which had been inoculated with vSVLS201M00. These results suggested that both amino acids determined the virulent phenotype, but that the 2A-20 site might be the major determinant for virulence.

An in situ hybridisation technique, based on oligodeoxynucleotide probes and tyramide signal amplification, is described for the detection of foot and mouth disease virus RNA in infected cells. Biotinylated oligodeoxynucleotide probes, with and without tyramide signal amplification, were compared. The tyramide signal amplification detection enhances by at least 100-fold the sensitivity of in situ hybridisation.

A series of recombinant viruses were constructed using infectious cDNA clones of the virulent J1’73 (large plaque phenotype) and the avirulent H/3’76 (small plaque phenotype) strains of swine vesicular disease virus to identify the genetic determinants of pathogenicity and plaque phenotype. Both traits could be mapped to the region between nucleotides (nt) 2233 and 3368 corresponding to the C terminus of VP3, the whole of VP1, and the N terminus of 2A. In this region, there are eight nucleotide differences leading to amino acid changes between the J1’73 and the H/3’76 strains. Site-directed mutagenesis of individual nucleotides from the virulent to the avirulent genotype and vice versa indicated that A at nt 2832, encoding glycine at VP1-132, and G at nt 3355, encoding arginine at 2A PRO -20, correlated with a large-plaque phenotype and virulence in pigs, irrespective of the origin of the remainder of the genome. Of these two sites, 2A PRO -20 appeared to be the dominant determinant for the large-plaque phenotype but further studies are required to elucidate their relative importance for virulence in pigs.

In February 2004 a highly pathogenic avian influenza outbreak erupted in the Fraser Valley of British Columbia, Canada. The index farm was a chicken broiler breeder operation comprising two flocks, 24 and 52 wk of age. Birds in the older flock presented with a mild drop in egg production and a small increase in mortality. Pathological specimens taken from the older flock were submitted to the provincial veterinary diagnostic laboratory from which an influenza A virus was isolated. While still under investigation by the provincial veterinary authorities, a spike in mortality was observed in birds belonging to the younger flock. Diagnostic material from both flocks was forwarded to the Canadian Food Inspection Agency's National Centre for Foreign Animal Disease. A low-pathogenicity H7N3 virus was detected in the older flock and a novel highly pathogenic H7N3 virus was found in specimens collected from the younger flock. Despite destruction and disposal of birds on the index farm, the virus spread to adjacent farms. Given the high density of poultry operations in the Fraser Valley and the high level of integration amongst industry support services, a total of approximately 17 million chickens, turkeys, ducks, geese, and speciality birds were put at immediate risk. Despite movement controls the virus spread and established itself in three distinct clusters. To prevent further spread, healthy, marketable birds outside of the surveillance areas were pre-emptively slaughtered. Although highly pathogenic avian influenza is a federal responsibility, the successful control and eradication of this outbreak would not have been possible without the cooperative involvement of federal and provincial diagnostic laboratories. The success of this collaboration was partly responsible for the formation of a national avian influenza laboratory network.

Sheep pox and goat pox are diseases of sheep and goats caused by pox virus. The variety and range of clinical signs produced by a single strains of virus in different breeds and age groups of animal tends to overlap those produced by different viruses within the same group or even different groups of pox viruses. Thus, contagious pustular dermatitis, easy to diagnose in countries considered free of sheep and goat pox, is probably frequently diagnosed as sheep or goat pox where the diseases co-exist. In the past, vaccinia infection of sheep and goats could also have been misdiagnosed.