Safety of orally administered, USP-compliant levothyroxine sodium tablets in dogs.

The safety of synthetic levothyroxine sodium tablets (Thyro-Tabs® Canine; LLOYD, Inc.) in dogs was evaluated in a randomized, sham-dose controlled, parallel-group study. Young, healthy, euthyroid Beagle dogs were randomized into four groups (four females and four males per group) and received single daily doses of 0×, 2× (0.044 mg/kg), 6× (0.132 mg/kg), or 10× (0.22 mg/kg) the labeled starting dose of 0.022 mg kg-1  day-1 for 182 days. Every 2 weeks, physical examinations, electrocardiology examinations, and sample collections for thyroid panel, hematology, serum biochemistry, coagulation panel, and urinalysis were performed. At the end of the study, the dogs were euthanized and full necropsies performed. The most overt finding was the expected dose-dependent increase in serum concentrations of total and free thyroxine with dose-dependent suppression of the hypothalamic-pituitary-thyroid axis as evidenced by decreased serum thyroid-stimulating hormone concentrations, decreased thyroid+parathyroid/body weight ratios, and a trend for decreased pituitary weight/brain weight ratios. Clinical signs of thyrotoxicosis (excitation, tachypnea, tachycardia) in the treated dogs were sporadic with no dose-response relationship. Other findings statistically associated with levothyroxine treatment were generally mild and not clinically important. In summary, doses of levothyroxine sodium up to 10× the labeled starting dose were well tolerated in healthy dogs.

Target animal safety study of meloxicam administered via transmucosal oral spray (Promist(®) technology) for 6 months in dogs.

This study evaluated the safety of meloxicam administered via transmucosal oral spray (TMOS) at 1, 2, 3 and 5 times the maximum proposed dose for 6 months in dogs. After baseline assessments, 40 Beagles (20 M, 20 F) were randomized to gender-balanced groups administered either water or meloxicam TMOS at 1, 2, 3 and 5 times the maximum proposed dose once daily for 26 weeks. Dogs were subjected to daily food consumption measurements and clinical and dose site observations. Periodic evaluations were made of body weight, physical examination, clinical pathology, urinalysis, buccal mucosal bleeding time (BMBT) and gastroduodenal endoscopy. At study completion, all dogs were subjected to gross necropsy. Histopathology was performed on tissues from dogs in groups 0X and 5X and from selected tissues in other dose groups. Clinical signs of previously reported NSAID-associated gastrointestinal upset were noted with higher frequency in meloxicam-dosed animals than in controls. Despite the presence of statistically significant effects on some clinicopathological variables, no toxicologically relevant dose-associated effects were determined on these or on food consumption, dose site observations, body weight, physical examination, urinalysis, BMBT, endoscopic examination or gross and histopathological examination of necropsy tissues.

Clinical efficacy and tolerance of meloxicam in dogs with chronic osteoarthritis.

A clinical trial was conducted to evaluate the safety and efficacy of the nonsteroidal anti-inflammatory drug meloxicam in dogs with chronic osteoarthritis. Forty clinical cases were enrolled in the 2-phase study. Phase 1 compared therapeutic efficacy and tolerance of meloxicam or placebo for 1 week. Phase 2 involved a 4-week evaluation of the drug's clinical efficacy and tolerance. Clinical efficacy was evaluated by using a scoring system that assessed specific lameness, general stiffness, painful rise, exercise intolerance, and behavior. Evaluations demonstrated significant reductions (P < 0.05) in clinical signs of osteoarthritis following 4 weeks of drug therapy. Side effects were minimal in extent and duration. The drug was accepted without problems in the majority of cases. The findings of this investigation suggest that the efficacy, tolerance, and formulation of meloxicam oral suspension make it well suited for the treatment of chronic osteoarthritis in the dog.

In vitro allergen-induced degranulation of pulmonary mast cells from horses with recurrent airway obstruction (heaves).

OBJECTIVE: To determine the capacity of pulmonary mast cells (PMC) to degranulate in response to various potential allergens and other secretagogues in horses with recurrent airway obstruction (heaves) and clinically normal horses before and after exposure to moldy hay. ANIMALS: 5 horses with heaves and 5 clinically normal horses. PROCEDURES: Heaves was characterized as an increased clinical respiratory score and maximum change in transpulmonary pressure of > 20 cm H2O after exposure. Bronchoalveolar lavage was performed during each period. Washed and resuspended cells were exposed for 20 minutes at 37 C with whole reconstituted freeze-dried preparations of Aspergillus fumigatus, Alternaria tenuis, and Ambrosia elatior, fungal extracts of Aspergillus fumigatus, Alternaria tenuis, and Micropolyspora faeni; A23187; and compound 48/80. Histamine release (HR) was used as a marker of degranulation. RESULTS: Compared with clinically normal horses, HR was significantly greater from PMC from horses with heaves during remission and exacerbation in response to whole preparations and extracts of Aspergillus fumigatus and whole preparations of Alternaria tenuis. Extracts of Alternaria tenuis caused significantly greater HR from PMC from horses with heaves during exacerbation. Histamine was also released from PMC in response to A23187 and to changes in osmolality of the medium, but only as a result of cell lysis by compound 48/80. CONCLUSIONS: Increased degranulation of PMC after antigenic challenge may contribute to the pathogenesis of heaves in horses. CLINICAL RELEVANCE: Strategies for prevention and treatment that attenuate degranulation of PMC may assist in the clinical management of horses with heaves.

Pulmonary eosinophilia associated with increased airway responsiveness in young racing horses.

Horses are known to acquire small airway disease (SAD), an allergen-induced naturally occurring syndrome of reversible obstructive lung disease accompanied by airway hyperresponsiveness and increased inflammatory cell numbers on bronchoalveolar lavage (BAL). This disorder has received scant attention in young racehorses. The purpose of the present report was to examine the effect of BAL eosinophilia in young racehorses on clinical examination, BAL, hematology, airway responsiveness, and on pulmonary function at rest and after a standardized exercise challenge. Five (3 males, 2 females; age 2.6 +/- 0.9 years) with a history of respiratory compromise and BAL eosinophil differential count > 5% and 6 controls (4 males, 2 females; age 3.5 +/- 1.0 years) training and performing to expectation with normal BAL cell differential (eosinophils < 1%) were studied. Respiratory system clinical examination was performed and expressed as a clinical score. Arterial blood gas measurements, CBC, and pulmonary function testing were performed at rest. Pulmonary mechanics measurements were repeated 1 hour and 20 hours after a standardized treadmill exercise challenge. Incremental histamine inhalation challenge was performed and the concentration of histamine effecting a 35% decrease in dynamic compliance (PC35CDyn) was determined. Significant differences were noted between and controls with regard to clinical score (P = .01), blood eosinophils (P = .04), BAL cell count (P = .04), BAL macrophage differential (P = .04), PC35CDyn (P = .008), and tidal volume and respiratory rate at 20 hours following exercise challenge (P = .05). We conclude that pulmonary eosinophilia and airway hyperresponsiveness are manifest in some young horses without overt airway obstruction at rest. We speculate that these may be early events in the natural progression of heaves.

Evaluation of an in vitro degranulation challenge procedure for equine pulmonary mast cells.

Pulmonary mast cells (PMC) are important components of the inflammatory process in equine allergic lung diseases such as heaves. Very little, however, is known of the degranulation kinetics of these cells and thus, their pathophysiologic role remains largely speculative. The purpose of this study was to develop a repeatable protocol for in vitro equine PMC degranulation. Five mature horses (sex: 2 M, 3 F; age: 8.8 +/- 6.5 y), historically free of pulmonary disease and normal on clinical respiratory examination, arterial blood gas analysis, pulmonary mechanics testing and histamine inhalation challenge, were studied. Bronchoalveolar lavage was performed on 4 separate occasions, at least 2 d apart, in a different lung lobe on each occasion. The lavage fluid was concentrated by centrifugation. Cells were resuspended in modified HEPES/Tyrode, assessed for viability by Trypan blue exclusion, and PMC concentration determined. Cell inocula containing 30,000 PMC were incubated with 10(-8) to 6 x 10(-5) M A23187. Cells were then separated by centrifugation and histamine release (HR) was determined by fluorometric assay. The procedure was readily performed and yielded sufficient PMC for 30 to 60 inocula per lavage. Maximal HR (34.4 +/- 16.1%) was obtained with 10(-5) M A23187. The degranulation process was largely complete by 20 min but cell lysis was negligible. The challenge was repeatable within horse and produced a mean coefficient of variability of 23.0% following 20 min incubation with 10(-5) M A23187. We conclude that equine PMC degranulation can be repeatably performed in vitro and speculate that this protocol may be useful in further studies on the pathophysiology and treatment of equine allergic lung diseases.

Treatment of feline otoacariasis with 2 otic preparations not containing miticidal active ingredients.

Two otic products not containing miticidal active ingredients were compared for the treatment of otoacariasis in 20 cats. It was concluded that treatment of feline otoacariasis can be achieved using products with an oil/wax base in conjunction with routine ear cleaning and total body parasitacide treatment.

Effect of 5-hydroxytryptamine type-2 receptor blockade on pulmonary function in calves with experimentally induced Pasteurella haemolytica pneumonia.

OBJECTIVE: To evaluate a 5-hydroxytryptamine type-2 receptor antagonist, metrenperone (MET), in alleviating respiratory distress associated with experimentally induced Pasteurella haemolytica pneumonia in feedlot calves. DESIGN: Double-blind controlled clinical trial. ANIMALS: 30 healthy 6- to 8-month-old Hereford-type calves (250 to 450 kg). PROCEDURE: Initial measurements were made of rectal temperature (RT), arterial blood gas (ABG) tensions, and pulmonary mechanics. Calves were then infected with P haemolytica in logarithmic phase of growth by intratracheal inoculation. 18 hours later, determination of RT and ABG tensions, and pulmonary function testing were repeated and calves were selected for inclusion in the study on the basis of having 2 of the following: respiratory rate > 50 breaths/min, RT > 40 C, or PaO2 > 20 mm of Hg below the baseline value. MET (0.1 mg/kg of body weight, IM) or an equivalent vehicle dose was then administered. RT, ABG, and pulmonary mechanics measurements were repeated at 0.5, 1, 2, 3, 4, 6, 12, and 24 hours after treatment. Calves were then euthanatized, and gross necropsy scoring and histologic examination were performed on the lungs. RESULTS: Infection with P haemolytica caused significant increases in RT and respiratory rate, and reduction in PaO2, PaCO2, and tidal volume 18 hours after inoculation. MET-treated calves and significantly reduced rectal temperature between 1 and 12 hours, compared with vehicle-treated calves. In addition, MET-treated calves had reduced respiratory rate with concomitantly increased tidal volume between 0.5 and 2 hours after treatment, compared with vehicle-treated calves. Necropsy revealed acute lobar bronchopneumonia in all 30 calves, but there was no difference in necropsy score between treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: MET may have an antipyretic effect on calves with pneumonia caused by P haemolytica. Its influence on pulmonary mechanics was minimal however, and it did not induce lung lesions in the short term.

Effect of sodium cromoglycate on light racehorses with elevated metachromatic cell numbers on bronchoalveolar lavage and reduced exercise tolerance.

Some young horses with clinical signs of small airway disease demonstrate increased metachromatic cell numbers on bronchoalveolar lavage. The purpose of this study was to determine the effect of sodium cromoglycate treatment on clinical signs, bronchoalveolar lavage cytology and bronchoalveolar lavage histamine parameters in these horses. Twelve racehorses (age: 3.4 +/- 1.6 years) with a history of respiratory embarrassment at exercise, clinical signs of obstructive airway disease and bronchoalveolar lavage metachromatic cell differential greater than 2% were selected. Horses were randomly assigned to receive either 200 mg sodium cromoglycate or saline placebo nebulized twice daily for 7 days. A clinical respiratory score was assigned and bronchoalveolar lavage was performed on each animal on days 0 and 7. Measurements were made of the following bronchoalveolar lavage fluid parameters: total nucleated cell concentration, differential cell percentage and concentration, supernatant and lysate histamine concentration, lysate: supernatant histamine ratio and metachromatic cell histamine content. Between the two evaluation periods, sodium cromoglycate treated horses demonstrated an improvement in respiratory score (P = 0.01) and a stabilizing of metachromatic cell histamine content (P = 0.04) when compared with placebo treated horses. We concluded that sodium cromoglycate is effective for the treatment of small airway disease in this population of young racehorses although the pharmacodynamics of this drug in the horse require further investigation.

Commercial contracts and the moral contract: a response to Nigel Cameron.

John E. Hare responds to Cameron's article by challenging the adequacy of the Hippocratic Oath as a basis for ethical medicine. The Oath promoted a "guild mentality" that is evident, for example, in modern medicine's resistance to alternative forms of practice. Christians need to "winnow" bioethical views, both those traditionally honored and those that confront us because of new medical developments.

Holographic color schlieren.

A 20-in (51-cm) diam schlieren system was convereted to a genrualized holographic flow visualization system. The system has been used successfully in producing the following types of visualization from a single holographic plate: three-dimensional photography, variable focus shadowgraph, variable knife-edge position schlieren, color-schlieren, and interferometry. All of these except for holographic color schlieren have previously been reported with varying degrees of success. This paper presents a technique for producing color schlierent photographs from holograms formed in the above system and shows preliminary results of the application. The method possesses a number of advantages over conventional color schlieren photography.