An in vitro study to determine the effectiveness of a patellar ligament/fascia lata graft and new tibial suture anchor points for extracapsular stabilization of the cranial cruciate ligament-deficient stifle in the dog

OBJECTIVE: (1) To determine whether an extracapsular patellar ligament/fascia lata graft would provide stability in the cranial cruciate ligament (CrCL)-deficient stifle comparable with that of the intact stifle. (2) To determine if different tibial anchor points would enhance stability of the CrCLdeficient stifle when compared with the standard fabellar-tibial suture (FTS) placement. STUDY DESIGN: Experimental. ANIMALS: Twenty-eight canine cadaver hind limbs. METHODS: Stifles were mounted in a jig and tested between loads of -65 and 80 N. After testing the intact CrCL, 4 stabilization techniques were tested after CrCL transection: lateral graft technique (LGT) and 3 FTS with different tibial anchor points. RESULTS: There were no significant differences in displacement between the LGT and standard FTS, between the LGT and the intact CrCL, or between the FTS and the intact CrCL, in either the Securos or the Screw-washer experiments. Stiffness of the intact CrCL was significantly greater than that of any stabilization technique and the cut CrCL. The standard FTS showed the least displacement of all suture stabilization techniques. Differences in stiffness were not significant between the suture stabilization techniques. CONCLUSIONS: Securely anchored, the LGT results in a reduction in drawer motion similar to that of the intact CrCL and the standard FTS. Altering the tibial anchor point for the FTS does not improve stiffness or enhance stabilization of the CrCL-deficient stifle. CLINICAL RELEVANCE: The LGT could be used for the treatment of CrCL ruptures in the dog. A clinical study is recommended.     

Multifocal cutaneous histiocytic sarcoma in a young dog and review of histiocytic cell immunophenotyping

A 9‐month‐old male Great Dane had progressive generalized nodular dermatopathy for several months. There were > 100 raised, alopecic, firm, painful nodules throughout the skin. Aspirates from several lesions yielded moderate numbers of irregularly round or polygonal to spindle‐shaped cells with mild to moderate anisocytosis and few inflammatory cells, and the cytologic interpretation was proliferation of mesenchymal or histiocytic cells. On histopathologic examination, nodules were composed of densely packed sheets of round to spindle‐shaped cells with mild anisokaryosis and low mitotic activity. Multifocal histiocytic sarcoma with a spindle‐cell pattern was diagnosed based on morphologic features and intense expression of CD18. Additional immunophenotypic analysis on frozen sections of tissue confirmed the diagnosis of histiocytic sarcoma; expression of CD18, CD45, CD1a, CD11b, and CD11c, limited expression of Thy‐1 (CD90) and CD80, and lack of expression of CD4, CD11d, and CD86 indicated that the cells were likely interstitial dendritic cells; a review of reactive and neoplastic dendritic cells is provided. Based on staging, internal organs were not affected. Sequential treatment with lomustine and doxorubicin failed to prevent progression of the cutaneous lesions, and the dog died 3 months after initial diagnosis. At necropsy, a focus of neoplastic cells was present in one lymph node, but except for skin other organs were not involved. The clinical presentation of histiocytic sarcoma may be unusual, and neoplastic cells may lack overt features of malignancy on cytologic and histopathologic examination. In some instances, immunophenotyping is required to differentiate histiocytic sarcoma from other histiocytic disorders.     

Magnetic resonance imaging features of feline intracranial neoplasia: retrospective analysis of 46 cats

The purpose of this retrospective study was to determine the magnetic resonance imaging (MRI) characteristics of feline brain tumors and to determine whether these characteristics can be used to accurately predict the histologic diagnosis. MRI scans of 46 cats with histologically confirmed brain tumors were reviewed, including 33 meningiomas, 6 lymphomas, 4 gliomas, 2 olfactory neuroblastomas, and 1 pituitary tumor. MRI features including axial origin, shape, location, signal intensity, contrast enhancement, peritumoral edema, and mass effect were reviewed and characterized for each tumor type. Tumor shape, axial origin, contrast enhancement, and degree of peritumoral edema aided in the identification of tumor type. Meningiomas were always extra-axial and were most often ovoid with marked contrast enhancement and mild peritumoral edema. Gliomas were always intra-axial with ring enhancement and generally caused more peritumoral edema than other tumors. The brain tumor was detected on MRI in 45 (98%) cats. Two blinded independent reviewers correctly identified 82% of all of the tumor types on the basis of MRI appearance alone. Thus, MRI is an excellent diagnostic tool for the detection of brain tumors in cats, and it provides important information to aid in the diagnosis of tumor type.     

Effects of testicular biopsy in clinically normal bulls

OBJECTIVE: To determine whether testicular needle biopsy is detrimental to testicular function in clinically normal bulls. DESIGN: Prospective study. ANIMALS: 6 mixed-breed mature bulls. PROCEDURE: A randomly selected testicle from each bull was biopsied with a 14-gauge needle biopsy instrument. Bulls were then evaluated over a 90-day period for changes in scrotal temperature and thermal patterns, ultrasonographic appearance, and quality of spermatozoa. At the end of the 90-day study, bulls were castrated, and testicles were examined grossly and histologically. RESULTS: Changes were detected in scrotal temperatures and thermal patterns and in the breeding soundness examination results during the first 2 weeks of the study. However, there were no long-term changes in semen quality over the course of the experiment. Hyperechoic areas were detected on ultrasonographic examination and corresponded to the areas of penetration by the biopsy instrument. Microscopic lesions that were indicative of testicular dysfunction were not found. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that testicular biopsy is a safe procedure in bulls. Testicular biopsy could possibly be used to further examine bulls that have less than satisfactory results for breeding soundness examinations.     

Mineral Nitrogen in a Crested Wheatgrass Stand: Implications for Suppression of Cheatgrass

Cheatgrass (Bromus tectorum L.) is an exotic annual grass causing ecosystem degradation in western US rangelands. We investigated potential mechanisms by which crested wheatgrass (Agropyron cristatum L. Gaertn., Agropyron desertorum [Fisch. {Ex Link} Scult.]) suppresses the growth and invasibility of cheatgrass. Research focused on monthly mineral soil N availability and the proportional concentration of NH₄⁺-N in a crested wheatgrass community by microsite (crested wheatgrass, unvegetated interspace, shrub subcanopy) and soil depth (0–15, 15–30 cm) over a 1-yr period. Mineral soil N in crested wheatgrass microsites ranged from 0.24 to 1.66 mmol · kg^-1 and was not appreciably lower than the other microsites or other ecosystems we have measured in the Great Basin. The molar proportion of NH₄⁺-N in the mineral N pool of crested wheatgrass averaged over 85% for the year and is significantly higher than the other microsites and far greater than other plant communities we have measured in the Great Basin. We conclude that crested wheatgrass does not suppress cheatgrass by controlling mineral N below a threshold level; rather, we hypothesize that it may limit nitrification and thereby reduce NO₃^--N availability to the nitrophile cheatgrass.     

Successful drug development despite adverse preclinical findings part 1: processes to address issues and most important findings

Unexpected adverse preclinical findings (APFs) are not infrequently encountered during drug development. Such APFs can be functional disturbances such as QT prolongation, morphological toxicity or carcinogenicity. The latter is of particular concern in conjunction with equivocal genotoxicity results. The toxicologic pathologist plays an important role in recognizing these effects, in helping to characterize them, to evaluate their risk for man, and in proposing measures to mitigate the risk particularly in early clinical trials. A careful scientific evaluation is crucial while termination of the development of a potentially useful drug must be avoided. This first part of the review discusses processes to address unexpected APFs and provides an overview over typical APFs in particular classes of drugs. If the mode of action (MoA) by which a drug candidate produces an APF is known, this supports evaluation of its relevance for humans. Tailor-made mechanistic studies, when needed, must be planned carefully to test one or several hypotheses regarding the potential MoA and to provide further data for risk evaluation. Safety considerations are based on exposure at no-observed-adverse-effect levels (NOAEL) of the most sensitive and relevant animal species and guide dose escalation in clinical trials. The availability of early markers of toxicity for monitoring of humans adds further safety to clinical studies. Risk evaluation is concluded by a weight of evidence analysis (WoE) with an array of parameters including drug use, medical need and alternatives on the market. In the second part of this review relevant examples of APFs will be discussed in more detail.     

Cerebrospinal fluid glutamine,tryptophan, and tryptophan metabolite concentrations in dogs with portosystemic shunts

OBJECTIVE: To determine whether glutamine (GLN), tryptophan (TRP), and tryptophan metabolite concentrations are higher in cerebralspinal fluid (CSF) dogs with naturally occurring portosystemic shunts (PSS), compared with control dogs. ANIMALS: 11 dogs with confirmed PSS and 12 control dogs fed low- and high-protein diets. PROCEDURE: Cerebrospinal fluid and blood samples were collected from all dogs. Serum and CSF concentrations of GLN, alanine, serine, TRP, 5-hydroxyindoleacetic acid (5-HIAA), and quinolinic acid (QUIN) were measured. RESULTS: Cerebrospinal fluid concentrations of GLN, TRP, and 5-HIAA were significantly higher in PSS dogs, compared with control dogs fed high- or low-protein diets. Cerebrospinal fluid QUIN concentration was significantly higher in PSS dogs, compared with control dogs fed the low-protein diet. Serum QUIN concentration was significantly lower in PSS dogs, compared with control dogs fed either high- or low-protein diets. CONCLUSIONS AND CLINICAL RELEVANCE: An increase in CNS GLN concentration is associated with high CSF concentrations of TRP and TRP metabolites in dogs with PSS. High CSF 5-HIAA concentrations indicate an increased flux of TRP through the CNS serotonin metabolic pathway, whereas high CSF QUIN concentrations indicate an increased metabolism of TRP through the indolamine-2,3-dioxygenase pathway. The high CSF QUIN concentrations in the face of low serum QUIN concentrations in dogs with PSS indicates that QUIN production from TRP is occurring in the CNS. High concentrations of QUIN and other TRP metabolites in the CNS may contribute to neurologic abnormalities found in dogs with PSS and hepatic encephalopathy.