Randomized controlled trial demonstrates nutritional management is superior to metronidazole for treatment of acute colitis in dogs.

OBJECTIVE: To describe the outcome of dietary management of canine noninfectious acute colitis with or without concurrent oral administration of metronidazole using a randomized controlled clinical trial. ANIMALS: 59 client-owned dogs with noninfectious acute colitis. PROCEDURES: Dogs with acute noninfectious colitis were enrolled in a 30-day diet trial after exclusion of parasitic infectious etiologies (fecal centrifugation floatation, Giardia/Cryptosporidium antigen testing) and systemic disease (CBC, biochemistry, urinalysis). Dogs were randomized into 3 placebo-controlled groups: group 1, easily digestible diet + placebo tablet; group 2, easily digestible diet + metronidazole tablet; and group 3, psyllium-enhanced easily digestible diet + placebo tablet. Dogs were evaluated serially using fecal scoring for time to remission, average fecal score, relapse after remission, and dysbiosis index. RESULTS: Median remission time was significantly different among the 3 groups (P < .01) with median times of 5 days (range, 4 to 10) for group 1, 8.5 days (range, 7 to 12) for group 2, and 5 days (range, 3 to 6) for group 3. Metronidazole addition affected the fecal dysbiosis index negatively at days 7 to 10. No adverse effects or complications were noted throughout the study. CLINICAL RELEVANCE: For canine noninfectious acute colitis, dietary management with an easily digestible diet with or without psyllium enhancement proved a superior management strategy compared to metronidazole. The omission of metronidazole reduced the adverse impact significantly on intestinal microbiota. Longitudinal clinical trials are necessary to compare the long-term response, stability, and complications associated with dietary management alone versus combined dietary and antimicrobial therapy for canine acute colitis.

Prevalence of AmpC- and Extended-Spectrum ß-Lactamase-Harbouring Enterobacteriaceae in Faecal Flora of a Healthy Domestic Canine Population.

In order to estimate the prevalence of AmpC- and ESBL ß-lactamase-producing Enterobacteriaceae in the faecal flora of a healthy domestic canine population, faecal samples were obtained from healthy dogs receiving routine parasitology screening at the Ohio State University Veterinary Medical Center, between January 2013 and April 2013. Samples were screened for the presence of AmpC and ESBL ß-lactamase phenotypes, and the clinically important genotypes, blaCMY and blaCTX-M , were confirmed via conventional PCR. Minimum inhibitory concentrations were determined for isolates and plasmids were characterized. Two hundred and twelve canine faecal samples were screened, of which 30 harboured isolates carrying the AmpC blaCMY , representing 14.2% of the population (95% CI: 9.4-18.9%). Nine samples harboured isolates that carried the ESBL blaCTX-M , representing 4.2% of the population (95% CI: 1.5-7.0%). Isolates containing blaCMY harboured multiple plasmid replicon types, while isolates containing blaCTX-M harboured few plasmid replicon types. Our results suggest that domestic dogs may serve as a reservoir for extended-spectrum cephalosporin resistance genes for other domestic animal populations as well as for their human companions. This represents a potential veterinary and public health risk that warrants further investigation and continued surveillance to ascertain the nature and extent of the risk. The high level of diversity of plasmid content among isolates harbouring blaCMY suggests broader dissemination relative to blaCTX-M isolates.

Elimination of hepatitis B virus surface antigen and appearance of neutralizing antibodies in chronically infected patients without viral clearance.

Seroconversion from hepatitis B surface antigen (HBsAg) to antibodies against HBsAg (anti-HBs) usually indicates resolution of hepatitis B virus (HBV) infection. Here, two HBV-infected patients with seroconversion to anti-HBs were found to be persistently positive for HBeAg and HBV DNA. Immunohistology of liver biopsies confirmed the expression of HBV proteins in the liver of one patient. The neutralizing ability of anti-HBs in patient sera was demonstrated by blocking HBV infection of primary tupaia hepatocytes. Analysis of the HBsAg-encoding region of HBV isolates from patients indicated the coexistence of heterogeneous HBV genomes in patients. The majority of recombinant variant HBsAg was reactive in HBsAg assays and was able to bind to anti-HBs. Circulating immune complexes (CIC) of HBsAg in patient sera could be detected by polyethylene glycol precipitation and trypsin digestion. Thus, neutralizing anti-HBs may appear in chronic HBV carriers for long periods but does not necessarily lead to complete viral clearance.

The prevalence of ovine herpesvirus-2 in 4 sheep breeds from different regions in South Africa.

About 90% of bovine malignant catarrhal fever (BMCF) PCR-positive cases in South Africa are caused by alcelaphine herpesvirus-1 (AlHV-1) and the other 10% by ovine herpesvirus-2 (OvHV-2). The prevalence of OvHV-2 in different sheep breeds in South Africa was determined in order to investigate whether the lower incidence of BMCF caused by OvHV-2 in comparison with AlHV-1 can be ascribed to a low incidence of the virus in sheep. A single-tube hemi-nested PCR was developed, evaluated and applied to detect OvHV-2 DNA. The prevalence of the virus in 4 sheep breeds from various regions in South Africa was shown to be 77%. No statistically significant difference was found amongst the sheep breeds tested.

Non-invasive approaches to visualize the endothelin axis in vivo using state-of-the-art molecular imaging modalities.

The endothelin axis plays a major role in cardiovascular diseases and a number of human cancers. This review summarizes the work that has been published in the past ten years using labeled endothelin receptor ligands for the visualization of endothelin receptor expression in vivo.

[Modern magnetic resonance procedures for assessing tumor response]. / Moderne MR-Verfahren zur Beurteilung der Tumorresponse.

Magnetic resonance imaging (MRI) is a mainstay in oncological imaging with respect to tumor detection, characterization and treatment monitoring. Besides quantifying metric changes of tumor tissue, a wide range of different other surrogate parameters of therapy response can be imaged and quantified by MRI. Early monitoring of treatment success is critical both for medical and economical reasons specifically with more expensive target-specific drugs entering the clinical arena. Dynamic contrast-enhanced (DCE) and steady state MRI can help to assess tumor perfusion and vessel permeability. The cellular state of tissue can be measured by diffusion-weighted imaging (DWI) and metabolic changes can be monitored by MR spectroscopy (MRS). New target-specific contrast agents potentially allow selective imaging of apoptotic events.This review aims to give a brief overview of new MR-based imaging approaches to assess tumor response to new target-specific therapy regimes, with special emphasis on anti-angiogenic and antivascular treatment effects.

Chemotherapy in metastatic malignant triton tumor: report on two cases.

Malignant triton tumor (MTT) is a rare, highly malignant nerve sheath tumor with rhabdomyoblastic differentiation. Initial debulking surgery followed by adjuvant therapy is the current treatment of choice, but has very limited efficacy when optimal cytoreduction is not achieved by surgical procedure. Neoadjuvant therapy for MTT, to potentially facilitate subsequent surgery, eradicate micrometastatic lesions and, therefore, improve the therapeutical outcome, has never before been presented in literature. Here, we report on the multimodal management of two cases of advanced and metastatic MTT. Treatment modalities involved neoadjuvant and adjuvant chemotherapy, surgical resection, and radiation. In both cases, integrated Positron Emission Tomography/Computed Tomography (PET/CT) emerged as an important diagnostic tool for the reliable assessment of MTT response and metabolic remission.

[Molecular and parametric imaging with iron oxides]. / Molekulare und parametrische Bildgebung mit Eisenoxiden.

Superparamagnetic iron oxide (SPIO) contrast agents, clinically established for high resolution magnetic resonance imaging of reticuloendothelial system containing anatomical structures, can additionally be exploited for the non-invasive characterization and quantification of pathology down to the molecular level. In this context, SPIOs can be applied for non-invasive cell tracking, quantification of tissue perfusion and target specific imaging, as well as for the detection of gene expression. This article provides an overview of new applications for clinically approved iron oxides as well of new, modified SPIO contrast agents for parametric and molecular imaging.

MR and optical approaches to molecular imaging.

With an increasing understanding of the molecular basis of disease, various new imaging targets have recently been defined that potentially allow for an early, sensitive, and specific diagnosis of disease or monitoring of treatment response. Different approaches to depict these molecular structures in vivo are currently being explored by the molecular imaging community. We briefly review methodologies for molecular imaging by magnetic resonance imaging and optical methods. Special emphasis is put on different contrast agent designs (e.g., targeted and smart probes). New technical developments in optical imaging are briefly discussed. In addition, current research results are put into a clinical perspective to elucidate the potential merits one might expect from this new research field.

Discrimination between sheep-associated and wildebeest-associated malignant catarrhal fever virus by means of a single-tube duplex nested PCR.

A single-tube duplex nested polymerase chain reaction (sdn-PCR) was developed for the detection of and discrimination between ovine herpesvirus-2 (OvHV-2) and alcelaphine herpesvirus-1 (AIHV-1). These viruses respectively cause sheep- and wildebeest-associated malignant catarrhal fever (SA-MCF and WA-MCF). In the first step of the sdn-PCR, two primers with high annealing temperatures based on conserved regions of the tegument genes were used for DNA amplification. In the second step, two primer sets based on variable regions of the respective OvHV-2 and AIHV-1 genes and with annealing temperatures > 11 degrees C below the primers used in the first step, were used. Internal regions of different sizes from amplicons produced in the first step were amplified. This single-tube test obviates the need for two separate assays to detect both viral types, thereby reducing time, labour and cost.

Imaging features of iliopsoas bursitis.

The aim of this study was firstly to describe the spectrum of imaging findings seen in iliopsoas bursitis, and secondly to compare cross-sectional imaging techniques in the demonstration of the extent, size and appearance of the iliopsoas bursitis as referenced by surgery. Imaging studies of 18 patients (13 women, 5 men; mean age 53 years) with surgically proven iliopsoas bursitis were reviewed. All patients received conventional radiographs of the pelvis and hip, US and MR imaging of the hip. The CT was performed in 5 of the 18 patients. Ultrasound, CT and MR all demonstrated enlarged iliopsoas bursae. The bursal wall was thin and well defined in 83% and thickened in 17% of all cases. The two cases with septations on US were not seen by CT and MRI. A communication between the bursa and the hip joint was seen, and surgically verified, in all 18 patients by MR imaging, whereas US and CT failed to demonstrate it in 44 and 40% of the cases, respectively. Hip joint effusion was seen and verified by surgery in 16 patients by MRI, whereas CT (4 of 5) and US ( n=12) underestimated the number. The overall size of the bursa corresponded best between MRI and surgery, whereas CT and US tended to underestimate the size. Contrast enhancement of the bursal wall was seen in all cases. The imaging characteristics of iliopsoas bursitis are a well-defined, thin-walled cystic mass with a communication to the hip joint and peripheral contrast enhancement. The most accurate way to assess iliopsoas bursitis is with MR imaging; thus, it should be used for accurate therapy planning and follow-up studies. In order to initially prove an iliopsoas bursitis, US is the most cost-effective, easy-to-perform and fast alternative.

Optical imaging of matrix metalloproteinase-2 activity in tumors: feasibility study in a mouse model.

PURPOSE: To develop an optical imaging method to determine the expression level of tumoral matrix metalloproteinase-2 (MMP-2) in vivo. MATERIALS AND METHODS: An optical contrast agent was developed that was highly activatable by means of MMP-2-induced conversion. Signal characteristics of the probe were quantified ex vivo with a recombinant enzyme. Animal tumor models were established with MMP-2-positive (human fibrosarcoma cell line, n = 4) and MMP-2-negative (well-differentiated mammary adenocarcinoma, n = 4) tumor cell lines. Both tumors were implanted into nude mice and were optically imaged after intravenous administration of the MMP-2-sensitive probe. RESULTS: The MMP-2-sensitive probe was activated by MMP-2 in vitro, producing up to an 850% increase in near-infrared fluorescent signal intensity. This activation could be blocked by MMP-2 inhibitors. MMP-2-positive tumors were easily identified as high-signal-intensity regions as early as 1 hour after intravenous injection of the MMP-2 probe, while contralateral MMP-2-negative tumors showed little to no signal intensity. A nonspecific control probe showed little to no activation in MMP-2-positive tumors. CONCLUSION: It is feasible to image MMP-2 enzyme activity in vivo by using near-infrared optical imaging technology and "smart" matrix metalloproteinase-sensitive probes.

Efficient radiological assessment of the internal snapping hip syndrome.

The aim of this study was to evaluate the diagnostic value/significance of various imaging techniques for demonstrating the underlying causative pathology of clinically suspected internal snapping hip syndrome. We intended to define the most efficient diagnostic imaging algorithm that leads to a specific definite therapy for this rare hip disorder. The imaging studies of 54 patients (43 women, 11 men, average age 58 years) with the clinical suspicion of internal snapping hip syndrome were compared for their diagnostic value/significance for finding the underlying pathology. Radiological workup included plain radiographs of the pelvis and hip joints (n=54), ultrasound (US) of the hip joints (n=29), computed tomography (CT) of the pelvis and proximal femur (n=17), and magnetic resonance imaging (MRI) of the pelvis/hip joint (n=21). In order to establish an efficient diagnostic algorithm we compared the diagnostic value of each imaging technique alone and in combination with the other methods. The underlying causative pathology could be established in 37% of patients (n=20) by the use of conventional radiographs alone and in 46% of the patients (n=25) by US alone, and in combination in 83% of the patients (n=45). By adding CT to the radiological workup, we established final diagnosis in 88% (in combination with X-ray; n=15/17) and 94% (together with X-ray and US; n=16/17) of the patients. Whenever MR imaging was used a causative pathology was found in all patients (100%; n=21). The most efficient radiological algorithm in the assessment of patients with internal snapping hip syndrome is the combination of plain radiography and US. MR imaging can be retained for unresolved and difficult cases.

Control of anthelmintic resistant endoparasites in a commercial sheep flock through parasite community replacement.

An effort was undertaken to replace a community of sheep endoparasites that had been classified as resistant to levamisole and albendazole with a community of more susceptible parasites using a dilution approach that could be integrated into the management of a commercial flock. For this study, pastures on this sheep farm were divided into two areas: north and south. Strategically timed anthelmintic treatments combined with pasture management reduced to nondetectable levels the endemic community of anthelmintic resistant parasites in this flock and on these pastures by early summer. A group of 102 ewes, lambs, and rams were experimentally infected with third stage larvae from the more susceptible community of parasites. These sheep then seeded the south pastures with the new parasite community, while sheep on the north pastures maintained the endemic resistant community. Despite its insensitivity as a technique for detecting anthelmintic resistance, fecal egg count reduction tests at the end of the grazing season indicated that the more susceptible parasites were present on the south pastures while resistant parasites were present on the north. The following grazing season, similar protocols were used to introduce the more susceptible parasites onto the north pastures. At the end of the grazing season, fecal egg count reduction tests indicated that the new community of parasites had become established on both groups of pastures of the farm.

In vivo molecular target assessment of matrix metalloproteinase inhibition.

A number of different matrix metalloproteinase (MMP) inhibitors have been developed as cytostatic and anti-angiogenic agents and are currently in clinical testing. One major hurdle in assessing the efficacy of such drugs has been the inability to sense or image anti-proteinase activity directly and non-invasively in vivo. We show here that novel, biocompatible near-infrared fluorogenic MMP substrates can be used as activatable reporter probes to sense MMP activity in intact tumors in nude mice. Moreover, we show for the first time that the effect of MMP inhibition can be directly imaged using this approach within hours after initiation of treatment using the potent MMP inhibitor, prinomastat (AG3340). The developed probes, together with novel near-infrared fluorescence imaging technology will enable the detailed analysis of a number of proteinases critical for advancing the therapeutic use of clinical proteinase inhibitors.

Ex vivo evaluation of novel miniaturized laser-induced interstitial thermotherapy applicators for effective small-volume tissue ablation.

RATIONALE AND OBJECTIVES: For effective small-volume tissue ablation in clinical and experimental settings, smaller laser-induced interstitial thermotherapy (LITT) applicator designs are required. The aim of this study was to compare the ablation properties of recently developed ultrasmall and small to standard LITT applicators. METHODS: Laser-induced interstitial thermotherapy was performed on liver samples using ultrasmall, small, and standard LITT applicators. Thermotherapy was monitored by magnetic resonance imaging, and lesion sizes were measured for each image. True lesion sizes were then determined macroscopically and by histology. RESULTS: For continuous laser application over 5 minutes, maximum power settings were 5 W for the ultrasmall and small applicators and 10 W for the standard applicator. Given identical LITT settings, lesion volume measured by magnetic resonance imaging was significantly larger and histological tissue damage was more severe with the ultrasmall and small applicators than with the standard applicator. CONCLUSIONS: Small and ultrasmall LITT applicators can be used for effective tissue ablation of small target volumes in experimental and clinical applications.

[Imaging of angiogenesis]. / Bildgebung von Angiogenese.

Angiogenesis of tumors has gained tremendous attention in the research community over the last years. Novel anti-angiogenic treatment protocols are currently in various phases of clinical testing. Thus, the major challenge for Radiological diagnostics is to develop imaging methods which reliably measure the angiogenic tumor burden as well as tumor response to anti-angiogenic treatment in vivo. This article intends to provide a brief overview of imaging strategies for angiogenesis and anti-angiogenic treatment.

[Progress in optical imaging]. / Fortschritte in der optischen Bildgebung.

Different optical imaging technologies have significantly progressed over the last years. Besides advances in imaging techniques and image reconstruction, new "smart" optical contrast agents have been developed which can be used to detect molecular targets (such as endogenous enzymes) in vivo. The combination of novel imaging technologies coupled with smart agents bears great diagnostic potential both clinically and experimentally. This overview outlines the basic principles of optical imaging and summarizes the current state of the art.

[Pathomorphology of laser-induced interstitial tumor thermotherapy of the liver]. / Pathomorphologie der Laser-induzierten interstitiellen Tumor-Thermotherapie an der Leber.

The aim of this study was to analyse pathomorphological findings after treatment with laser induced tumor thermotherapy (LITT) on liver tissue and to correlate the results with magnetic resonance imaging. LITT was performed ex vivo and in vivo using a Neodym-YAG-Laser. Lesions were monitored by MR-thermometry ex vivo and by contrast-enhanced MRI in vivo. After LITT the lesions were examined macroscopically, histologically, and electronmicroscopically. LITT-induced tissue damage was qualitatively evaluated, classified, and quantified by means of digital image analysis. Four different zones of tissue damage were identified within the lesions. Adjacent to the applicator the tissue was completely ablated while more peripheral lesions exhibited only sublethal cell damages seen by EM. In vivo the pattern of tissue injury followed the lobular architecture of the liver tissue. Ultrastructural examination revealed only in areas of minor tissue injury intact sinusoidal patterns. MRI overestimated the diameter of the core zone of complete tissue ablation both ex vivo and to a lesser extent in vivo.