Effect of pre-cardiac and adult stages of Dirofilaria immitis in pulmonary disease of cats: CBC, bronchial lavage cytology, serology, radiographs, CT images, bronchial reactivity, and histopathology.

A controlled, blind study was conducted to define the initial inflammatory response and lung damage associated with the death of precardiac stages of Dirofilaria immitis in cats as compared to adult heartworm infections and normal cats. Three groups of six cats each were used: UU: uninfected untreated controls; PreS I: infected with 100 D. immitis L3 by subcutaneous injection and treated topically with selamectin 32 and 2 days pre-infection and once monthly for 8 months); IU: infected with 100 D. immitis L3 and left untreated. Peripheral blood, serum, bronchial lavage, and thoracic radiographic images were collected from all cats on Days 0, 70, 110, 168, and 240. CT images were acquired on Days 0, 110, and 240. Cats were euthanized, and necropsies were conducted on Day 240 to determine the presence of heartworms. Bronchial rings were collected for in vitro reactivity. Lung, heart, brain, kidney, and liver tissues were collected for histopathology. Results were compared for changes within each group. Pearson and Spearman correlations were performed for association between histologic, radiographic, serologic, hematologic and bronchoalveolar lavage (BAL) results. Infected cats treated with selamectin did not develop radiographically evident changes throughout the study, were heartworm antibody negative, and were free of adult heartworms and worm fragments at necropsy. Histologic lung scores and CT analysis were not significantly different between PreS I cats and UU controls. Subtle alveolar myofibrosis was noted in isolated areas of several PreS I cats and an eosinophilic BAL cytology was noted on Days 75 and 120. Bronchial ring reactivity was blunted in IU cats but was normal in PreS I and UU cats. The IU cats became antibody positive, and five cats developed adult heartworms. All cats with heartworms were antigen positive at one time point; but one cat was antibody positive, antigen negative, with viable adult females at necropsy. The CT revealed early involvement of all pulmonary arteries and a random pattern of parenchymal disease with severe lesions immediately adjacent to normal areas. Analysis of CT 3D reconstruction and Hounsfield units demonstrated lung disease consistent with restrictive pulmonary fibrosis with an interstitial infiltrate, absence of air trapping, and decrease in total lung volume in Group IU as compared to Groups UU and PreS I. The clinical implications of this study are that cats pretreated with selamectin 1 month before D. immitis L3 infection did not become serologically positive and did not develop pulmonary arterial hypertrophy and myofibrosis.

Lung histopathology, radiography, high-resolution computed tomography, and bronchio-alveolar lavage cytology are altered by Toxocara cati infection in cats and is independent of development of adult intestinal parasites.

This study presents clinical findings after oral ingestion of Toxocara cati eggs which resulted in rapid pulmonary lung migration and parenchymal disease, noted on clinically relevant diagnostic methods. Further, the study investigated the efficacy of pre-infection applications of preventative medication on larval migration through the lungs. A third aim of the study was to determine if adult cats infected with T. cati developed lung disease. Cats in infected groups were administered five oral doses of L3 T. cati larvae. Four-month-old specific pathogen free (SPF) kittens were divided into three groups (six per group): an infected untreated group, an uninfected untreated control group, and an infected treated group (topical moxidectin and imidacloprid, Advantage Multi for Cats, Bayer Healthcare LLC). Six 2- to 3-year-old adult multiparous female SPF cats were an infected untreated adult group. The cats were evaluated by serial CBCs, bronchial-alveolar lavage (BAL), fecal examinations, thoracic radiographs, and thoracic computed tomography (CT) scans and were euthanized 65 days after the initial infection. Adult T. cati were recovered in infected untreated kittens (5/6) and infected untreated adults (5/6) in numbers consistent with natural infections. Eggs were identified in the feces of most but not all cats with adult worm infections. No adult worms were identified in the uninfected controls or the infected treated group. All cats in the infected groups, including treated cats and untreated cats without adult worms, had lung pathology based on evaluation of radiography, CT scans, and histopathology. The infected cats demonstrated a transient peripheral eosinophilia and marked eosinophilic BAL cytology, but normal bronchial reactivity based on in vivo CT and in vitro ring studies. Lung lesions initially identified by CT on day 11 were progressive. Thoracic radiographs in infected cats had a diffuse bronchial-interstitial pattern and enlarged pulmonary arteries. Pulmonary arterial, bronchial, and interstitial disease were prominent histological findings. Infected treated cats had a subtle attenuation but not prevention of lung disease compared to infected cats. Significant lung disease in kittens and adult cats is associated with the early arrival of T. cati larvae in the lungs and is independent of the development of adult worms in the intestine. These data suggest that while the medical prevention of the development of adult parasites after oral exposure to T. cati is obviously beneficial, this practice even with good client compliance will not prevent the development of lung disease which can alter clinical diagnostic methods.

Nasal tumor with widespread cutaneous metastases in a Golden Retriever.

An intact, 8-year-old, male Golden Retriever dog was presented for evaluation of a nasal mass and approximately 30 firm, raised, variably ulcerated dermal and subcutaneous masses. Histopathology of both nasal and multiple skin masses revealed multiple nonencapsulated, infiltrative masses comprising clusters, anastomosing trabeculae, and packets of neoplastic, round to ovoid, hyperchromatic cells with marked nuclear molding. Surrounding the neoplastic cells was a marked stromal response in which many of the spindle-shaped cells expressed muscle-specific actin and had ultrastructural features consistent with myofibroblasts. A literature search indicates that this is the first report in a peer-reviewed journal of cutaneous metastasis of a nasal neuroendocrine tumor in any domestic animal species.

Benefit-risk assessment of vitamin D supplementation.

UNLABELLED: Current intake recommendations of 200 to 600 IU vitamin D per day may be insufficient for important disease outcomes reduced by vitamin D. INTRODUCTION: This study assessed the benefit of higher-dose and higher achieved 25-hydroxyvitamin D levels [25(OH)D] versus any associated risk. METHODS AND RESULTS: Based on double-blind randomized control trials (RCTs), eight for falls (n = 2426) and 12 for non-vertebral fractures (n = 42,279), there was a significant dose-response relationship between higher-dose and higher achieved 25(OH)D and greater fall and fracture prevention. Optimal benefits were observed at the highest dose tested to date for 700 to 1000 IU vitamin D per day or mean 25(OH)D between 75 and 110 nmol/l (30-44 ng/ml). Prospective cohort data on cardiovascular health and colorectal cancer prevention suggested increased benefits with the highest categories of 25(OH)D evaluated (median between 75 and 110 nmol/l). In 25 RCTs, mean serum calcium levels were not related to oral vitamin D up to 100,000 IU per day or achieved 25(OH)D up to 643 nmol/l. Mean levels of 75 to 110 nmol/l were reached in most RCTs with 1,800 to 4,000 IU vitamin D per day without risk. CONCLUSION: Our analysis suggests that mean serum 25(OH)D levels of about 75 to 110 nmol/l provide optimal benefits for all investigated endpoints without increasing health risks. These levels can be best obtained with oral doses in the range of 1,800 to 4,000 IU vitamin D per day; further work is needed, including subject and environment factors, to better define the doses that will achieve optimal blood levels in the large majority of the population.

Identification and characterization of murine alternatively spliced tissue factor.

Tissue factor (TF) is a transmembrane glycoprotein that initiates coagulation and plays a critical role in regulating hemostasis and thrombosis. We have recently reported a naturally occurring, soluble form of human tissue factor (asTF) generated by alternative splicing. This splice variant has a novel C-terminus with no homology to that of the full-length TF (flTF), lacks a transmembrane domain, and is active in the presence of phospholipids. Mouse models offer unique opportunities to examine the relative importance of flTF and asTF in mediating thrombosis, the response to arterial injury, and ischemic damage. To that end, we have identified and characterized murine asTF (masTF). Like the human splice variant, masTF lacks a transmembrane domain and has a unique C-terminus. We have generated antibodies specific to masTF and murine flTF (mflTF) to examine the expression of both forms of TF. masTF antigen is widely and abundantly expressed, with a pattern similar to that of mflTF, in adult tissues, in experimentally induced thrombi, and during development. These studies demonstrate that masTF contributes to the pool of total TF and may thus play an important role in mediating TF-dependent processes.

Effect of anaesthesia of the palmar digital nerves on proximal interphalangeal joint pain in the horse.

REASONS FOR PERFORMING STUDY: Anaesthesia of the palmar digital nerves is claimed to attenuate lameness in some horses that are lame because of pain in the proximal interphalangeal (PIP) joint. OBJECTIVE: To determine the response of horses with pain in the PIP joint to anaesthesia of the palmar digital nerves. METHODS: Horses were video recorded trotting before and after induction of pain in the PIP joint and 10 mins after anaesthesia of the palmar digital nerves. The palmar digital nerves were anaesthetised 3 times at different sites, and the video recorded gaits were scored subjectively. RESULTS: The median lameness score of gaits after administration of 2% mepivacaine 1 cm proximal to the cartilages of the foot was not significantly different from the median lameness score before anaesthesia of the palmar digital nerves (P > or = 0.05), although that of 1 of 6 horses improved markedly. The median lameness score was significantly (P < or = 0.05) improved after mepivacaine was administered 2 and 3 cm proximal to the cartilages of the foot. CONCLUSIONS: The PIP joint is unlikely to be anaesthetised when the palmar digital nerves are anaesthetised at the proximal margin of the cartilages of the foot. POTENTIAL RELEVANCE: Pain within the PIP joint cannot be excluded as a cause of lameness when lameness is attenuated by anaesthesia of the palmar digital nerves at any site proximal to the proximal margin of the cartilages of the foot.

Rapid generation of thrombin by atheroma and platelets.

Rapid re-occlusion of an atheromatous vessel after angioplasty may occur through yet incompletely known mechanisms. Atheromatous plaque has been shown to contain tissue factor (TF) activity. When atheroma extracts (atheroma) and platelets are incubated together a powerful prothrombinase is rapidly generated, which neither platelets nor atheroma alone can generate. Large amounts of thrombin were generated in minutes by many atheroma-platelet mixtures. However in these mixtures, generation of factor (F)Xa activity was not enhanced, but was in fact decreased by platelet tissue factor pathway inhibitor (TFPI) activity. Leukocytes had no appreciable effect in these short-term experiments. Although levels of factor VII and FX in atheroma were extremely low, antibodies to each of these factors inhibited prothrombinase formation. So did an antibody to factor V. A FXa inhibitor, DX 9065a, was very effective in preventing prothrombinase generation. These findings may explain the rapid occlusion that has been observed after angioplasty and point to avenues of prevention.

Dietary supplements: how they are used and regulated.

Overall use of nutrient and botanical dietary supplements (DS) has increased for years across all major categories. Many DS are simply taken as part of a healthy lifestyle, but some are used to reduce risk of or modulate risk factors for specific chronic diseases, such as heart disease (vitamin E, folic acid, garlic), cancer (selenium, vitamin E, garlic) and certain birth defects (folic acid). Other DS are used for short-term benefits such as sleep management (valerian, melatonin) and enhanced physical performance (pyruvate, creatine). DS are regulated under food law, but with certain provisions that apply only to DS. Thus, DS are eligible for Food and Drug Administration (FDA)-authorized health claims under the Nutrition and Labeling Education Act (NLEA). Health claims have already been authorized for folic acid and calcium, but not for several others. In 1994, when the Dietary Supplement Health and Education Act (DSHEA) was passed, it expanded and clarified the definition of DS, specified additional requirements for safety and provided for four types of claims of nutritional support. These include prevention of classic nutritional deficiencies, structure or function (S/F) effects, mechanisms for S/F effects and general well-being. Although S/F effects result from both foods and drugs, representation that a product will treat, cure, mitigate or diagnose a disease is reserved for drugs. Therefore, the wording of S/F claims for DS has become a difficult issue in the proposed DS labeling regulations.

Magnetic resonance imaging features of brain stem abscessation in two cats.

Premortem magnetic resonance imaging (MRI) was performed in two cats with brain stem abscessation confirmed post mortem by histology and recovery of multiple bacterial species. The MRI features of the abscesses were distinctive and included a thick and marked enhancement of the abscess capsule and extension of the lesion from a tympanic bulla in one cat. A focal area of increased signal intensity was present on T2-weighted images. A circumscribed area of decreased signal intensity was surrounded by a ring of increased signal intensity on precontrast T1-weighted images. A center of decreased signal intensity with a thick, markedly enhanced abscess capsule was observed on post contrast T1-weighted images. These findings are compared to the current experimental and clinical literature of brain abscess. The underlying pathogenesis of MRI features is reviewed.

Computed tomographic characteristics of multilobular tumor of bone involving the cranium in 7 dogs and zygomatic arch in 2 dogs.

Computed tomography (CT) images of nine dogs with a multilobular tumor of bone of the head were reviewed. The CT characteristics of the neoplasms involving the calvarium (n = 7) were rounded, well defined with a fine granular, nonhomogeneous bone opacity usually in the occipital region. Cranial vault invasion (5 of 7) was commonly found with a significant portion of the mass within the vault. The neoplasms involving the zygomatic arch (n = 2) were also generally rounded and well defined but with a more coarse granular appearance. The common CT findings were best seen when the images were viewed in a bone window.

Low-field magnetic resonance imaging of the equine tarsus: normal anatomy.

The objective of this study was to define the normal gross anatomic appearance of the adult equine tarsus on a low-field magnetic resonance (MR) image. Six radiographically normal, adult, equine tarsal cadavers were utilized. Using a scanner with a 0.064 Tesla magnet, images were acquired in the sagittal, transverse and dorsal planes for T1-weighted and the sagittal plane for T2-weighted imaging sequences. Anatomic structures on the MR images were identified and compared with cryosections of the imaged limbs. Optimal image planes were identified for the evaluation of articular cartilage, subchondral bone, flexor and extensor tendons, tarsal ligaments, and synovial structures. MR images provide a thorough evaluation of the anatomic relationships of the structures of the equine tarsus.

Active tissue factor shed from human arterial smooth muscle cells adheres to artificial surfaces.

Through a series of in vitro assays, this study outlines a flow-mediated process by which active tissue factor (TF), the prime initiator of coagulation, may be transferred from the plasma membrane of vascular smooth muscle cells (VSMCs) to that of artificial surfaces such as those typically associated with intravascular implants. Studies with quiescent and activated rat VSMCs demonstrated that pathologically high shear stresses (tau(w) = 250 dyn cm(-2)) resulted in the loss of TF activity from the cell surface. Subsequent experiments with human VSMCs showed that VSMCs continuously release active TF into their extracellular medium, presumably in the form of lipid vesicles or microparticles, and that fluid shear stress (tauw = 50 dyncm(-2)) or chemical agonists (A23187) can significantly accelerate this release. Experiments with a wide array of polymeric and metallic materials showed that the TF shed from VSMCs was able to adhere to these surfaces and promote the activation of coagulation factor X (FX) at the material surface. Extracellular TF bound strongly to both uncoated and human plasma coated surfaces under a wide range of hemodynamic shear stresses (0-20 dyncm(-2)). When an extracellular, VSMC-derived TF mixture was perfused over Ti 6-4 surfaces, the adhesion of TF was found to be time-dependent, gradually accumulating on the material surface over time. Thus an important criterion in the design or success of intravascular devices may be related to their ability to interact with TF, shed from cell surfaces. This is especially important as TF may lead to thrombotic complications, the products of which may also increase cellular proliferation.

Coccygeal muscle injury in English Pointers (limber tail).

A condition colloquially referred to as "limber tail" and "cold tail" is familiar to people working with hunting dogs, primarily Pointers and Labrador Retrievers. The typical case consists of an adult dog that suddenly develops a flaccid tail. The tail either hangs down from the tail base or is held out horizontally for several inches from the tail base and then hangs straight down or at some degree below horizontal. Initially, the hair on the dorsal aspect of the proximal tail may be raised and dogs may resent palpation of the area 3-4 inches (8-10 cm) from the tail base. Most dogs recover spontaneously within a few days to weeks. Anecdotal reports suggest that anti-inflammatory drugs administered within 24 hours after onset hasten recovery. Less than one half of affected dogs experience a recurrence. Affected Pointers almost always have a history of prolonged cage transport, a hard workout the previous day, or exposure to cold or wet weather Most owners and trainers familiar with the condition do not seek veterinary assistance. In cases where people are not familiar with this disease, other conditions such as a fracture, spinal cord disease, impacted anal glands, or prostatic disease have been incorrectly diagnosed. We examined 4 affected Pointers and found evidence of coccygeal muscle damage, which included mild elevation of creatine kinase early after onset of clinical signs, needle electromyographic examination showing abnormal spontaneous discharges restricted to the coccygeal muscles several days after onset, and histopathologic evidence of muscle fiber damage. Specific muscle groups, namely the laterally positioned intertransversarius ventralis caudalis muscles, were affected most severely. Abnormal findings on thermography and scintigraphy further supported the diagnosis.

Effect of hydration on signal intensity of gelatin phantoms using low-field magnetic resonance imaging: possible application in osteoarthritis.

Five gelatin phantoms were constructed to study the effect of matrical hydration on magnetic resonance imaging (MRI) signal intensity using a low-field strength imager. Water content of the phantoms ranged from 75 to 95% weight/weight. Signal intensity values of each phantom were measured using five imaging sequences: proton density, T1-weighted, T2-weighted, inversion recovery with short inversion time, and inversion recovery with long inversion time. There was significant positive correlation (p < .05) of signal intensity with differences in hydration using the T2-weighted sequence and the inversion recovery sequence with short inversion time. Significant negative correlations (p < .05) were found with T1-weighted imaging and the inversion recovery sequence with long inversion time. In a second part of the study, in vivo focal variations in MRI signal intensity were evaluated in a canine cranial cruciate ligament deficient model of osteoarthritis. Signal intensity measurements were obtained from multiple areas of articular cartilage to identify an initial stage in osteoarthritis that is characterized in part by increased hydration of articular cartilage. At 6 weeks post-transection of the cranial cruciate ligament, an increase in signal intensity was detected in the articular cartilage of the weight-bearing portion of the lateral femoral condyle and the caudal portion of the medial tibial condyle with T1-weighted imaging. The increase in signal intensity may reflect increased proteoglycan synthesis by chondrocytes that also occurs early in the pathogenesis of osteoarthritis.

Low-field magnetic resonance imaging of early subchondral cyst-like lesions in induced cranial cruciate ligament deficient dogs.

Six healthy adult male mongrel dogs underwent cranial cruciate ligament transection in the left stifle. Survey radiography of both stifles and low-field (0.064 T) MRI of the left stifle were performed preoperatively and at 2, 6, and 12 weeks postoperatively. Focal changes in signal intensity were seen with MRI in the subchondral bone of the medial tibial condyle at 2 and 6 weeks postoperatively. At 12 weeks postoperative, a cyst-like lesion was detected using MRI in the subchondral bone of the medial tibial condyle in 4 of 6 dogs and a less defined lesion at this site in the remaining 2 dogs. The cyst-like lesion was spherical in shape and showed typical characteristics of fluid with low signal intensity on T1-weighted images, high signal intensity on T2-weighted images and high signal intensity on inversion recovery images. The lesion was seen in the subchondral bone of the caudal medial and/or middle region of the tibial plateau slightly cranial to the insertion of the caudal cruciate ligament. No subchondral cysts were seen in the tibia on radiographs. Histopathologically, the tibia was characterized by a loose myxomatous phase of early subchondral cyst formation.

Low-field magnetic resonance imaging of the canine stifle joint: normal anatomy.

Low-field magnetic resonance imaging (MRI) was performed on the stifle joints of four normal adult mongrel dogs using a 0.064 Tesla scanner. Markers were placed on each stifle joint to serve as reference points for comparing gross sections with the images. A T1-weighted sequence was used to image one stifle joint on each dog in the sagittal plane and the other stifle joint in the dorsal plane. The dogs were euthanized immediately following MRI and the stifle joints frozen intact. Each stifle joint was then embedded in paraffin, again frozen, and sectioned using the markers as reference points. On T1-weighted images, synovial fluid had low signal intensity (dark) compared to the infrapatellar fat pad which had a high signal intensity (bright). Articular cartilage was visualized as an intermediate bright signal and was separated from trabecular bone by a dark line representing subchondral bone. Menisci, fibrous joint capsule, and ligamentous structures appeared dark. In the true sagittal plane, the entire caudal cruciate ligament was often seen within one image slice. The patella was visualized as an intermediate bright signal (trabecular bone) surrounded by a low intensity signal (cortical bone). The trochlea and the intercondylar notch were difficult areas to analyze due to signal volume averaging of the curved surface of these areas and the presence of several types of tissues.