Liquid chromatographic determination of coumarin anticoagulants in tablets: collaborative study

A liquid chromatographic method for the determination of coumarin anticoagulants in tablets was collaboratively studied by 7 laboratories. The method uses an octadecylsilane-bonded microparticulate column, tetrahydrofuran-methanol-water-acetic acid mobile phase, and photometric detection at 311 nm. Each collaborator received samples of warfarin sodium, phenprocoumon, and dicumarol as a synthetic composite and as commercial individual and composited tablets. Pooled average assay values for synthetic and commercial tablet samples of warfarin sodium were 101.6 and 99.5%, respectively, with a combined reproducibility SD of 2.38% (CV = 2.37%) and combined repeatability SD of 1.49% (CV = 1.49%). Pooled average (SD) assay values for dicumarol and phenprocoumon commercial samples were 98.0 (2.27) and 101.3% (4.00), respectively. The content uniformity determinations of 2 mg warfarin sodium and 25 mg dicumarol tablets indicated average tablet contents (range) of 99.5% (91.0-116.0) and 98.0% (89.8-108.8), respectively. The method has been approved interim official first action.     

Coastal Chip: A chipping potato variety resistant to heat stress

Coastal Chip is a medium-late maturing potato chipping variety suitable for production in locations along the east coast of the United States where heat stress reduces internal quality of tubers. It yields as well as the variety Atlantic but is not as susceptible to heat necrosis. The specific gravity of Coastal Chip averages approximately 0.010 less than Atlantic at locations subject to heat stress. In the seed producing areas of Maine it’s specific gravity averages approximately 0.005 less than that of Atlantic. Tubers are round, netted-skinned, and have moderately deep stem and bud ends. Chips from Coastal Chip are slightly lighter in color than those produced by Atlantic. In mid-Atlantic states where heat stress adversely affects chip color Coastal Chip processes into chips for a slightly longer period of time after harvest than does Atlantic. Glycoalkaloid content of Coastal Chip averaged 7.9 mg/100 g fresh tissue. Sunburned (green) tubers of Coastal Chip develop purple streaks that remain following processing. Hills must be properly covered to reduce losses. Coastal Chip is resistant to race A of the golden nematode (Globodera rostochiensis) and potato virus A. It is tolerant to Verticillium wilt, more susceptible to common scab and Rhizoctonia than Atlantic and susceptible to potato virus X.     

Plasma and Pulmonary Fluid Endothelin in Horses with Seasonal Recurrent Airway Obstruction

Background: Summer pasture-associated recurrent airway obstruction (SPA-RAO), a seasonal airway obstructive disease of horses, is characterized by clinical exacerbation after exposure to pasture during warm months of the year. Endothelin (ET)-1, potent bronchoconstrictor, mitogen, secretagogue, and proinflammatory mediator, has been implicated in the pathogenesis of asthma and equine heaves.
Hypothesis: Immunoreactive ET-1 concentrations increase during clinical exacerbation and return to basal values during periods of disease remission.
Animals: Twelve horses, 6 affected with SPA-RAO and 6 nonaffected.
Methods: Prospective, observational study. Bronchoalveolar lavage fluid (BALF), arterial and venous plasma samples, and clinical variables were obtained from affected horses during clinical exacerbation and remission. Samples and data of nonaffected horses were collected during the summer and winter on dates similar to affected horses. Immunoreactive ET-1 was determined using a commercial ELISA.
Results: The median and range ET-1 concentrations (pg/ml) in arterial (1.3, 0.7–1.8) and venous (1.3, 1.2–1.7) plasma and in BALF (0.3, 0.2–0.4), and pulmonary epithelial lining fluid (PELF) (25.5, 21–50) were greater in affected horses during clinical exacerbation compared with remission ( P < .01). The concentrations of immunoreactive ET-1 were greater in affected horses during clinical exacerbation compared with nonaffected horses ( P < .05).
Conclusions and Clinical Importance: During clinical exacerbation of SPA-RAO, ET-1 is increased in circulation and pulmonary secretions. Intervention with ET receptor antagonists should provide further information on the role of ET-1 in SPA-RAO.     

Neurokinin receptors in recurrent airway obstruction: A comparative study of affected and unaffected horses

The purpose of the study was to compare in vitro airway responses to neurokinin A & B (NKA and NKB) and expression of NK-2 receptors in airways of horses affected and unaffected with recurrent airway obstruction (RAO). Neurokinin-A, an inflammatory mediator belonging to the tachykinin family of neuropeptides, causes bronchoconstriction by binding to NK-2 receptors. Neurokinin-B is a lesser-known neuropeptide that acts on NK-3 receptors. Horses were placed into RAO-affected and RAO-unaffected groups based on their history, clinical scoring, and pulmonary function testing. Lung tissue from each lobe was collected for immunohistochemical staining for NK-2 receptors. Cumulative concentration-response relationships were determined on bronchial rings (4-mm wide) collected and prepared from the right diaphragmatic lung lobe to graded concentrations (half log molar concentrations 10⁻⁷M to 10⁻⁴M) of NKA and NKB. The results showed that NKA caused significantly greater contraction than NKB in both groups. In RAO-affected horses, both agents produced significantly greater bronchial contractions than those in the RAO-unaffected horses. Immunohistochemical staining showed that the overall NK-2 receptor distribution was significantly increased in bronchial epithelium and smooth muscles of bronchi and pulmonary vessels of RAO-affected than RAO-unaffected horses. The findings indicate that NK-2 receptors are up-regulated in RAO, suggesting that NK-2 receptor antagonists may have some therapeutic value in controlling the progression of airway hyperreactivity in horses affected with RAO.     

In vitro susceptibility patterns of Aspergillus and Fusarium species isolated from equine ulcerative keratomycosis cases in the midwestern and southern United States with inclusion of the new antifungal agent voriconazole

Objective  To evaluate and compare the in vitro susceptibility of Aspergillus and Fusarium spp. isolated from horses with ulcerative keratomycosis, address regional differences in equine keratomycosis isolates, and provide susceptibility data to update prior studies.
Animal studied  Fourteen horses with ulcerative keratomycosis.
Procedures  Banked fungal isolates from equine corneal ulcers (eight Aspergillus spp. and six Fusarium spp.) were identified at The University of Texas Health Science Center at San Antonio. In vitro minimum inhibitory concentration and susceptibility to natamycin, fluconazole, itraconazole, voriconazole, ketoconazole, and miconazole were determined for each isolate.
Results  Fungi were significantly more susceptible to voriconazole than to natamycin, itraconazole, fluconazole, and ketoconazole, but miconazole susceptibility did not differ significantly from voriconazole. Aspergillus spp. were most susceptible to voriconazole, miconazole, and itraconazole, which were significantly better to fluconazole and ketoconazole. Fusarium spp. susceptibility was greatest to natamycin and voriconazole and lowest to itraconazole and ketoconazole. Fusarium spp. were significantly less susceptible to itraconazole and ketoconazole compared to natamycin. No significant differences in susceptibility were found when isolates from Florida were compared with isolates from other states.
Conclusions and clinical relevance  Based on in vitro evidence, voriconazole appears to be the most effective antifungal for initial treatment of equine keratomycosis in the midwestern and southern United States. Results are comparable with previous studies in that isolated fungi from equine keratomycosis cases showed consistently poor susceptibility to fluconazole. Organisms isolated in different geographic locations of the midwestern and southern United States appeared to have similar patterns of antifungal susceptibility.     

Serum total thyroxine and thyroid stimulating hormone concentrations in dogs with behavior problems

The aim of this case controlled study was to determine whether dogs with behavioral problems have evidence of abnormal thyroid function on routine screening tests for hypothyroidism. The hypothesis of the study was that thyroid function, as assessed by serum total thyroxine (TT4) and serum thyroid stimulating hormone (thyrotropin) (TSH) concentrations, is normal in most dogs with behavioral problems. Concentrations of TT4 and TSH in 39 dogs with behavior problems presenting to a veterinary behavior referral clinic (abnormal behavior group), were compared with TT4 and TSH concentrations in 39 healthy control dogs without behavior problems presenting to 5 community veterinary practices (control group). Dogs in the control group were matched for age and breed with the abnormal behavior group. Dogs with behavioral problems had higher TT4 concentrations than dogs without behavioral problems (t-test: t = 2.77, N = 39, P = 0.009), however none of the TT4 values were outside the reference range. There was no significant difference in TSH concentration between the 2 groups. Two dogs with behavior problems and 1 dog without behavior problems had results suggestive of hypothyroidism. All other dogs were considered to be euthyroid. There was no evidence to support a diagnosis of hypothyroidism in the majority of dogs with behavior problems in this study. The higher concentration of TT4 in dogs with behavior problems suggests, however, that alteration in thyroid hormone production or metabolism may occur in some dogs with behavior problems. Further studies that include additional indicators of thyroid status such as serum total triiodothyronine, serum, free thyroxine, and anti-thyroid antibody concentrations are necessary to further evaluate the significance of this finding.     

Canine and feline urolithiasis: Examination of over 50 000 urolith submissions to the Canadian Veterinary Urolith Centre from 1998 to 2008

This study reports on trends in canine and feline urolithiasis in Canada during the past 10 years. Age, sex, breed of animals and mineral composition from 40 637 canine and 11 353 feline bladder uroliths submitted to the Canadian Veterinary Urolith Centre between 1998 and 2008 were recorded. Struvite and calcium oxalate uroliths comprised > 85% of all uroliths submitted. In dogs, the number of struvite submissions has declined and the number of calcium oxalate submissions has increased. Struvite uroliths were most common in female dogs and calcium oxalate uroliths in male dogs. The shih tzu, miniature schnauzer, bichon frisé, lhasa apso, and Yorkshire terrier were the breeds most commonly affected for both struvite and calcium oxalate uroliths. Urate uroliths were most common in male dalmatians. In cats, struvite submissions declined and calcium oxalate submissions remained constant. Struvite and calcium oxalate uroliths were common in domestic, Himalayan, Persian, and Siamese cats. Urate uroliths were over-represented in Egyptian maus.     

ULTRASONOGRAPHIC AND CLINICOPATHOLOGIC FINDINGS IN 21 DOGS WITH INTESTINAL ADENOCARCINOMA

In a retrospective study of 21 dogs with intestinal adenocarcinoma, the signalment, clinical presentation, laboratory findings, ultrasonographic features, treatment, and outcome were reviewed. Anorexia (n = 16), vomiting (n = 15), diarrhea (n = 10), and weight loss (n = 9) were the most common clinical signs reported. Ultrasonographic features that were evaluated included location, length, wall thickness, echogenicity, regional motility, layering, regional lymphadenopathy, and fluid accumulation proximal to the lesion site. All lesions were transmural and associated with complete loss of wall layering. Maximum wall thickening at the lesion site ranged from 7 to 17 mm (median 12 mm, mean 11.9 mm). Most of the dogs had a lesion measuring from 23 to 63 mm in length, (median 40 mm, mean 42 mm). Most intestinal lesions were poorly echogenic and had an irregular lumen. Fluid accumulation proximal to the lesion site was identified in 17 of 21 dogs, and in 13 of 17 dogs the fluid accumulation was considered moderate to severe. Regional lymphadenopathy and/or nodular mesentery/omentum were noted in 12 of 21 dogs. The tumor was located in small intestine for 15 dogs and in the colon for the remaining 6 dogs. Fifteen dogs were treated by surgical resection of the intestinal mass. Their median survival time was 233 days. Only gender appeared to influence survival. Female dogs lived a median of 28 days, whereas male dogs lived a median of 272 days.     

Intravenous administration of 9-aminocamptothecin to dogs with lymphoma

A colloidal dispersion formulation of 9‐aminocamptothecin (9‐AC) was administered intravenously to 10 dogs with previously untreated, spontaneously occurring, multicentric lymphoma. The dogs received a 72‐h infusion of 9‐AC at a rate of 46.5–51.25 µg m^?2 h^?1 (total dose range 3.35–3.69 mg m^?2). This dose range was associated with myelosuppression, consisting principally of neutropenia with a nadir at 7 days following the start of infusion. Neutropenia and thrombocytopenia were the most common toxicoses and are most likely to be dose‐limiting toxicities; low‐grade gastrointestinal signs were rarely seen. Concentrations of 9‐AC lactone, as well as clinical toxicities, compare favourably with those found in humans. Tumour responses were seen in all treated dogs. Response to other chemotherapy, following cessation of 9‐AC treatment, was not obviously compromised even in dogs clinically resistant to 9‐AC. 9‐AC is a novel treatment drug for canine lymphoma, which appears to show great promise.