A true congenital pancreatic cyst in a dog.

BACKGROUND: True congenital pancreatic cysts are a rare pathological process reported within feline and human literature. To date there has been no documented case of a true congenital cyst affecting a canine patient. The objective of this case report is to document the clinical findings, diagnostic investigations, surgical treatment, histopathological diagnosis and long-term outcome of a dog with a true pancreatic cyst. CASE PRESENTATION: A 5-month-old crossbreed dog was presented with a six-week history of abdominal pain, apparent bilateral pelvic limb weakness, reluctance to walk and intermittent vomiting and diarrhoea. An abdominal ultrasound examination performed by the dog's primary care veterinarian identified a large intra-abdominal structure of unclear origin. A computed tomographic examination identified a large ovoid structure measuring 156 mm in length, 95 mm in height and 89 mm in width and apparently originating from the left limb of the pancreas. An exploratory coeliotomy was performed and a partial pancreatectomy was performed to allow complete removal of the cystic structure. Histopathological analysis of sections of the wall of the large fluid-filled cyst identified a thick fibromuscular wall lined by a well regimented hyperplastic tall columnar epithelium with basally located round to ovoid nuclei featuring fine chromatin stippling and abundant apically located and surface mucin, concurrent with a true congenital pancreatic cyst. A long-term follow-up of twenty-nine months identified no clinical signs of recurrence. CONCLUSION: A partial pancreatectomy and en bloc excision of a true pancreatic cyst provided an excellent long-term outcome in a dog.

Pathobiology of rabies virus and the European bat lyssaviruses in experimentally infected mice.

A comparison of the clinicopathology of European bat lyssavirus (EBLV) types-1 and -2 and of rabies virus was undertaken. Following inoculation of mice at a peripheral site with these viruses, clinical signs of rabies and distribution of virus antigen in the mouse brain were examined. The appearance of clinical signs of disease varied both within and across the different virus species, with variation in incubation periods and weight loss throughout disease progression. The distribution of viral antigen throughout the regions of the brain examined was similar for each of the isolates during the different stages of disease progression, suggesting that antigen distribution was not associated with clinical presentation. However, specific regions of the brain including the cerebellum, caudal medulla, hypothalamus and thalamus, showed notable differences in the proportion of virus antigen positive cells present in comparison to other brain regions suggesting that these areas are important in disease development irrespective of virus species.

Pathology associated with a human case of rabies in the United Kingdom caused by European bat lyssavirus type-2.

Human infection with the rabies-related virus European bat lyssavirus type-2 (EBLV-2) has only been reported on two occasions. Here we report the pathology observed within spinal cord and visceral tissues associated with EBLV-2 infection for the first time. Neuronal labelling with an anti-rabies nucleocapsid monoclonal antibody was observed and appeared indistinguishable from the labelling reported from human infection with rabies virus.

Comparative pathological study of the murine brain after experimental infection with classical rabies virus and European bat lyssaviruses.

European bat lyssaviruses (EBLVs) types 1 (EBLV-1) and 2 (EBLV-2) cause rabies in terrestrial species, but the pathological changes associated with neuroinvasion have yet to be fully elucidated. Swiss OF-1 mice were inoculated peripherally with strain RV61 (classical rabies virus), RV1423 (EBLV-1) or RV1332 (EBLV-2) to compare the nature and extent of histopathological changes produced. Inoculated animals developed varying degrees of non-suppurative encephalitis, and lyssavirus infection was confirmed by the detection of viral antigen. The lesions produced, which included perivascular cuffs and gliosis, were more severe after RV1423 or RV1332 infection than after RV61 infection. Perivascular cuffs were mainly localized to caudal brain regions, irrespective of the infecting strain; after RV1332 infection, however, they were particularly abundant, being composed of large numbers of inflammatory cells. T cells were the predominant lymphocytic component of the inflammatory infiltrate in both the Virchow-Robin space and the brain parenchyma. Viral antigen, which was widespread throughout the brain, was apparently unrelated to the degree of cuffing. The study suggested that there was increased immune activation after inoculation with strain RV1423 or RV1332, particularly the latter, but that this did not affect the final outcome.

Inflammatory responses in the nervous system of mice infected with a street isolate of rabies virus.

Rabies virus causes severe encephalitis that is invariably fatal for the victim. However, the contribution of the virus and the host to damage of the CNS is unclear. In order to investigate this we studied the neuropathology and CNS gene expression patterns in a murine model of rabies using a 'street' isolate RV61. This virus was derived from a human case of disease. In this model, infection of the CNS progresses rapidly following inoculation in the periphery, leading to extensive virus replication in the brain and the development of disease. However, previous studies have found little evidence of inflammation and lymphocyte infiltration in many regions of the CNS of infected mice. During the current study virus replication was detected in the dorsal root ganglia (DRG), spinal cord, brain and salivary gland at 11 days postinfection (dpi). Mononuclear cell infiltration was observed in the DRG and to a lesser extent, the spinal cord. Immunolabelling demonstrated that T-lymphocytes were the dominant population of infiltrating cells. Murine innate immune response gene transcripts were detected in the brain as early as 5 dpi. At 11 dpi, coincidentwith the onset of disease, elevated levels of mRNA transcripts were recorded for type-1 (alpha and beta) and type-2 interferon (gamma) and certain chemokines (CCL5 and CXCL10) with chemotactic properties for T-cells. We suggest that damage to the DRG and spinal cord could be due to a combination of both virus infection and the infiltration of T-cells.

Experimental infection of foxes with European bat lyssaviruses type-1 and -2.

Experimental studies have been undertaken to assess the susceptibility of silver foxes to bat variants of rabies virus, namely European Bat Lyssaviruses (EBLVs). Both EBLV-1 and EBLV-2 have been isolated in European bats since 1954, in Eptesicus serotinus and Myotis species, respectively. Since 2000, the number of reported cases has increased largely due to the improvement of the surveillance of bat rabies virus throughout Europe. Although over >800 EBLVs cases have been reported in bats in Europe, EBLV-1 and -2 viruses are rarely reported to infect humans and terrestrial animals. The study presented here shows that the sensitivity of silver foxes is low when infected with EBLVs via the intramuscular route; in contrast all animals infected via intracranial inoculation succumbed to the experimental challenge. The mortality rate was 100% for both EBLV-1 (approximately 4.5 log) and EBLV-2 (approximately 3.0 log). This data suggests that the susceptibility of foxes to EBLV-1 and EBLV-2 is low and that the transmission (spillover) and adaptation of EBLVs from a bat to a fox may be theoretically possible but unlikely.

Ability of rabies vaccine strains to elicit cross-neutralising antibodies.

Two European Bat Lyssaviruses (EBLV-1 and EBLV-2) have been identified (n > 750 cases) in European bat species. In addition, EBLVs have been detected as "spillover" cases in three humans, one stone marten and four sheep. A further concern is the interaction of companion animals with infected bats and the possibility of subsequent lyssavirus infection. Cat-bat interactions represent approximately 32 % (n = 398) of passive lyssavirus surveillance submissions at the Veterinary Laboratories Agency (VLA) (1987-2004). Cats therefore represent a potentially significant spillover host. This study evaluated the ability of rabies vaccine antibodies to neutralise EBLVs using modified fluorescent antibody virus neutralisation (FAVN) assays (EBLV-1, EBLV-2). We examined vaccinated human, dog and cat sera in two classes; (i) FAVN-CVS titres > or = 0.5-5.0 IU/ml (n = 34, 79 and 54, respectively), and (ii) > 5.0 IU/ml (n = 22, 21 and 32 respectively). Most sera (approximately 80 %) with higher titres were able to neutralise both EBLV-1 and -2 regardless of the vaccine received. Only a proportion of those with low titres were capable of neutralising either EBLV-1 (27-92 %) or EBLV-2 (38-92 %) or both EBLVs (27-79 %). The cat sera constitute the lower end of each range. More animals that had received LEP based vaccines were able to neutralise EBLVs than those that had received PV based vaccines. The continuing occurrence of non-classical lyssaviruses in Europe emphasizes the need for continual surveillance of bats and other species.

Early dissolution of a morsellised impacted silicate-free bioactive glass in metaphyseal defects.

The purpose of this study was to evaluate the biological properties of idealized, morsellised impacted Corglaes, a soluble silicate-free glass. Twenty-two sheep underwent implantation of pellets in six metaphyseal defects in both rear limbs. Particle size distribution of all aggregates (except the autograft) approached the ideal logarithmic grading line and all implants were impacted to a standard compactive effort. Treatment groups consisted of (1) empty defect (negative control), (2) autograft (positive control), (3) allograft (clinical control), (4) allograft idealized with Corglaes, (5) 50/50 allograft/Corglaes and (6) Corglaes. Defects were sealed with polymethylmethacrylate. Healing of the defects was evaluated at 7 weeks (n=6) and 14 weeks (n=16) with computed tomography, histology, and histomorphometry. Remnants of Corglaes were found within one of the defects 7 weeks after implantation. Defects filled with mixtures containing 50% or 100% Corglaes were less dense, contained less bone and more fibrous tissue than defects with allograft, autograft, or allograft idealized with Corglaes. Allograft idealized with Corglaes may be considered for impaction grafting in revision hip arthroplasty, as well as local delivery of antibiotics. However, further studies and potential revision of the agent are required before mixtures containing concentrations of Corglaes equal to or higher than 50% can be recommended.

Biodegradable controlled release glass in the repair of peripheral nerve injuries.

The experiments in this paper were concerned with the recovery of function and ease of application of an entubulation technique using a biodegradable, controlled release glass tube (CRG) for the repair of a transected peripheral nerve. The peroneal nerves of 15 New Zealand White rabbits were repaired with either a CRG tube filled with freeze-thawed muscle, or a conventional freeze thawed muscle graft (FTMG). These were compared with controls in which a CRG was used to enclose the cut ends of a nerve separated by a 1 cm gap. Electrophysiological and morphometric assessment was carried out 6 months after repair. No statistical difference was found in any test between the FTMG and the CRG tube filled with freeze thawed muscle. The CRG tube and 1 cm gap produced inferior levels of recovery of function when compared with the other two repair groups.

Multiresolution elastic image registration.

We have developed a multiscale algorithm for elastic (or molded) alignment of images. There is a wide array of medical applications of elastic (as opposed to strictly rigid) alignment: Subtraction of previous images from current ones to identify changes is perhaps the most obvious. We present preliminary results of this molding technique on a variety of images, and conclude with some closing remarks about this and future directions and goals of this work.

Elastic image registration using correlations.

We have developed a multiscale algorithm for elastic registration of images. Rigid registration has many applications but it is often limited by distortions in the images. For example, different views of the same object produce distortions. Common examples of slightly different views producing a distortion can be found in medical imaging, such as matching a current mammogram or chest radiograph with one from a previous year, and in remote sensing, such as matching images taken from different satellite positions. We have developed two methods of elastic registration. Both are multiscale but one used an iterative minimization of the local error and the other uses a windowed correlation. We present preliminary results of the elastic registration method used on windowed correlations.

In vitro nerve repair--in vivo. The reconstruction of peripheral nerves by entubulation with biodegradeable glass tubes--a preliminary report.

Biodegradeable "controlled release" inorganic polymer glass tubes can be manufactured to fit the dimensions of any nerve and their rate of solubility can be adjusted to encompass the time taken for nerve regeneration. They have been used in a number of biological applications. The facial nerve was repaired in a group of five sheep by entubulation with biodegradeable glass tubes. The sheep were assessed 10 months after repair and compared with a similar sized group of normal sheep. It was found that while there was a reduction in the peak velocity of conduction in the repaired nerves and in the range of conduction velocities, the minimum conduction velocity was within normal limits. There was a diminution in all of the measured variables of nerve morphometry but in no case did this reach statistical significance. These findings are consistent with the view that regeneration of the nerves had taken place to a degree at least as effective as that seen in nerves of a similar size repaired by conventional means.

Haemocompatiblity of controlled release glass.

There are many medical applications which benefit from the use of soluble biomaterials, including the sustained release of drugs over a precise period of time, or temporary conduits for controlling nerve regrowth. We have manufactured a series of phosphate-based controlled release glasses (CRGs) in which the solubility could be controlled by varying the concentration of CaO and Na2O. Fibres of the CRG containing iron and cerium were placed into direct contact with human neutrophils and macrophages in tissue culture for 2.5 and 24 h respectively and the responses analysed by scanning electron microscopy (SEM) and confocal microscopy. The supernatants were analysed for the cytokine IL-1beta by enzyme-linked immunosorbent assay (ELISA). Disks of CRG of various compositions were placed in contact with whole blood for 30 min and platelet adhesion assessed by SEM. Activation of platelets, granulocytes and complement were quantified by ELISA for beta-thromboglobulin, elastase and iC3b. Intrinsic coagulation activation was measured by timing the clotting of recalcified plasma. Only the cerium fibre inhibited IL-1beta release from macrophages. No platelet adhesion was observed to any disk composition. Three compositions containing MgO inhibited plasma clotting and showed an insignificant level of complement activation. This study has demonstrated the development of a number of compositions of CRG, which have great potential in a wide variety of biomedical applications.

Soft tissue response to glycerol-suspended controlled-release glass particulate.

Vesicoureteral reflux and urinary incontinence have previously been treated by various means including the endoscopic delivery of injectable bulking materials such as silicone micro-implants, PTFE implants, glass particles, fat and bovine collagen. These first three materials do not degrade and collagen requires frequently repeated injections in order to sustain the restored continence provided. Vesicoureteric reflux in children usually resolves independently before the age of five. Correction is required before this, because treatment by prophylactic antibiotics is frequently unsuccessful in preventing breakthrough infection. The ideal material for injection should have large particles to avoid migration, inject easily and controllably, be non-toxic and dissolve over the period of time by which time the kidney will be mature. Three different controlled-release glass (CRG) granule compositions have been prepared by Giltech Ltd, and suspended in a suitable carrier medium (in this case glycerol). The degradable glasses, which have two different size ranges of 200-300 and <53 microm, and three different solution rates, were injected intramuscularly into the dorso-lumbar region of rats. Histological analysis of cryostat cut section after time periods of 2 d, 4 and 9 wk, and 6 mon has been performed. Histology sections were stained for neutrophils and macrophages using enzyme histochemistry. ED1 (monocytes and immature macrophages), ED2 (mature tissue macrophages), CD4 (helper/inducer T-lymphocytes and macrophages), CD8 (suppressor/cytotoxic T-lymphocytes), Interleukin-1beta, IL-2 (activated T-lymphocytes), Major Histocompatibility Complex (MHC) class II (activated macrophages and activated B-lymphocytes), alpha-beta (T-lymphocytes) and CD45RA (B lymphocytes) antibodies have been used to stain immunohistochemically each sample. This study demonstrates that particulate, degrading glass is stimulating an inflammatory response in soft tissue at time periods up to 6 mon. It should be noted that very small particulate, fast degrading glass is leading to tissue necrosis and should not be considered further for these applications. However, larger particulate, slower degrading materials are demonstrating effective potential for stress incontinence applications.

Two applications of wavelets and related techniques in medical imaging.

We present two applications of wavelet and related techniques to problems arising in medical imaging. Both make considerable use of the edge detection and classification properties of wavelet-type representations. First we describe simple and effective techniques for image denoising and contrast enhancement based on the multiscale edge representation of images. These techniques are sufficiently flexible to successfully address the varying requirements posed by several different medical imaging modalities in common use today. Experimental results are presented to illustrate the application of these techniques to various types of medical images. Next we describe adapted waveform encoding, a technique for magnetic resonance imaging. One advantage of this technique is that it can be used to efficiently encode edge features of the object being imaged. This has a particular diagnostic application in tracking heart wall thickness during the cardiac cycle, which we present along with some experimental results along this line. We also present an analysis of the signal-to-noise ratios of images formed with this technique, as this is a factor of paramount importance in MRI. The fact that wavelet schemes tend to concentrate energy near edge features makes the result rather different than that found in standard Fourier based approaches. We indicate an exciting potential application of our technique: reducing spectral leakage in phosphorus spectroscopy.

Wavelet transform domain filters: a spatially selective noise filtration technique.

Wavelet transforms are multiresolution decompositions that can be used to analyze signals and images. They describe a signal by the power at each scale and position. Edges can be located very effectively in the wavelet transform domain. A spatially selective noise filtration technique based on the direct spatial correlation of the wavelet transform at several adjacent scales is introduced. A high correlation is used to infer that there is a significant feature at the position that should be passed through the filter. The authors have tested the technique on simulated signals, phantom images, and real MR images. It is found that the technique can reduce noise contents in signals and images by more than 80% while maintaining at least 80% of the value of the gradient at most edges. The authors did not observe any Gibbs' ringing or significant resolution loss on the filtered images. Artifacts that arose from the filtration are very small and local. The noise filtration technique is quite robust. There are many possible extensions of the technique. The authors see its applications in spatially dependent noise filtration, edge detection and enhancement, image restoration, and motion artifact removal. They have compared the performance of the technique to that of the Weiner filter and found it to be superior.

Wavelet-encoded MR imaging.

Wavelet encoding is presented and compared to phase encoding. In wavelet encoding a distribution of spins is excited by a slice selective RF pulse; for each repetition time the distribution excited has the profile of a wavelet at different scale and translation. The spin density can be reconstructed with an inverse wavelet transform. Wavelet encoding has three advantages over phase encoding: (1) there is no Gibb's ringing from partial volume effects, (2) the effective repetition time can be 36 times the repetition time for a 256 x 256 image, and (3) motion artifacts are local and dramatically reduced. Using wavelet encoding, a 256 x 256 T2-weighted projection image can be acquired in 33 s.

Filtering noise from images with wavelet transforms.

A new method of filtering MR images is presented that uses wavelet transforms instead of Fourier transforms. The new filtering method does not reduce the sharpness of edges. However, the new method does eliminate any small structures that are similar in size to the noise eliminated. There are many possible extensions of the filter.

Prophylactic minitracheotomy in lung resections. A randomized controlled study.

Thirty consecutive patients undergoing lung resections were randomized into two groups: Group A (n = 15) received minitracheotomy postoperatively and group B (n = 15) were control patients. Postoperative respiratory course was monitored by serial clinical assessments, chest x-ray examination, arterial blood gases, sputa bacterial cultures, and the patient's requirement and response to chest physiotherpy. The two groups were similarly matched in age (mean 58.5 years), smoking habits, pulmonary functions, and surgical procedures. Postoperative pulmonary complications of collapse/consolidation developed in 11 patients (two in group A and nine in group B) (p less than 0.03). Four patients (all in group B) required nimitracheotomy in addition to antibiotics and chest physiotherapy to treat their pneumonia. Chest physiotherapy requirement was less in group A than in group B, with a mean number of sessions of seven in group A and eight in group B and a mean total time of 92 minutes in group A and 112 minutes in group B. The mean duration of minitracheotomy was 4.13 days. Minor temporary symptoms resulted from the minitracheotomy in eight patients (42%) and included discomfort, voice changes, subcutaneous emphysema, and stridor. There was one case of long-term morbidity (5%)-skin scarring from wound infection at the site of the minitracheotomy. No postoperative deaths resulted. We conclude that the prophylactic use of minitracheotomy is safe and effective in decreasing postoperative respiratory complications in patients undergoing lung resections.

Controlled silver-releasing polymers and their potential for urinary tract infection control.

Calcium phosphate controlled release glass has been developed as a biocompatible vehicle for the sustained delivery of antibacterial silver ions. The solution rate in the presence of physiological fluids can be made constant over the design life of the product and one application in urinary tract infection control is outlined.