Oral pharmacokinetics of carbamazepine in dogs from commercial tablets and a cyclodextrin complex.

The extent of absorption of carbamazepine from a 2-hydroxypropyl-beta-cyclodextrin/carbamazepine complex was significantly greater and the rate of absorption was faster when compared with an immediate-release carbamazepine tablet in the dog. Six dogs were dosed orally in a two-way crossover study in which the tablet was compared with an equivalent dose of the complex in solution. The area under the curve of concentration versus time for the complex was 5.6 times greater than the tablet, whereas the mean time to reach maximum concentration for the tablet was 1.4 hours versus 0.5 hours for the complex. The complex, therefore, had a greater rate and extent of absorption. A rapidly acting and better absorbed carbamazepine product has the potential to decrease the daily dose of carbamazepine, increase its utility as emergency treatment of epileptic seizures, and provide an acceptable alternative dosage form in patients who are unable to swallow tablets.

Latent dichlorvos neurotoxicity detected by vagal tone monitoring in dogs.

Dichlorvos (dimethyl 2,2-dichlorovinyl phosphate) was administered orally to German Shorthair Pointer dogs at approximately 60 mg/kg (twice the usual clinical dose). Plasma and erythrocyte cholinesterase (ChE) was monitored prior to, 90 min, and 180 min post-ingestion. 2-PAM (20 mg/kg IV) and atropine sulfate (0.022 mg/kg IM) were administered 90 min after the dichlorvos to paired treated and control dogs. The telemetered electrocardiographic (ECG) signal was analyzed by a Vagal Tone Monitor (VTM) to yield mean heart period (msec) and an estimate of the amplitude of respiratory sinus arrhythmia (V in natural log values of msec2) for five min intervals. Dichlorvos did not cause cholinomimetic symptoms even though blood cholinesterase was significantly inhibited (plasma -51.3% and erythrocyte -43.7%). The atropine sulfate treatment resulted in the expected vagolytic effects in both the control and the dichlorvos treated dogs, but the atropine effects were attenuated in the latter dogs. Three weeks later, ChE activity was not significantly depressed in the dichlorvos treated dogs, and their V responses to atropine were more similar to the responses in control dogs.

Plasma theophylline concentration and lung function in ponies with recurrent obstructive lung disease.

Six ponies with recurrent obstructive lung disease were studied during two separate 60 min periods while receiving constant equal volume infusions of either aminophylline or sterile water. Dynamic lung compliance, pulmonary resistance, respiratory rate, tidal volume, blood gas tensions and heart rate were measured. Plasma samples were obtained for determination of theophylline concentrations before, and at 10 min intervals during, the infusion period. Excitability was assessed subjectively at these same time periods. The plasma theophylline concentrations in ponies were well predicted by a previously published model of theophylline pharmacokinetics in the horse. Sterile water had no effect on lung function. Aminophylline produced significant changes in lung function compared to baseline values, including a decrease in resistance at 30 min when the mean plasma theophylline concentration was 59 +/- 14 mumol/litre and an increase in compliance at 60 mins at a mean plasma theophylline concentration of 102 +/- 23 mumol/litre. Excitement was noted between 40 and 50 mins in all ponies (mean plasma theophylline concentration 74 +/- 20 and 84 +/- 24 mumol/litre, respectively). Heart rate increased at 50 mins. The therapeutic range for intravenous (iv) theophylline concentration in 'heavey' ponies therefore appears to be between 59 and 84 mumol/litre when aminophylline is administered iv. Below 59 mumol/litre there was no consistent bronchodilator activity and above 84 mumol/litre excitement and tachycardia limited the usefulness of the drug.

Tidal breathing flow-volume loops in healthy and bronchitic cats.

Tidal breathing flow-volume loops (TBFVL) were obtained from 19 healthy cats and 7 cats with chronic bronchial disease. Peak inspiratory flow (PIF) occurred late in the inspiratory cycle and was preceded by a gradual but more linear increase in the flow rate. Peak expiratory flow (PEF) occurred early during expiration and was followed by a curvilinear decrease in flow to a point near the end of expiration where flow ceased. The loops obtained were generally reproducible. The mean coefficient of variation (CV) for TBFVL indices of healthy cats ranged from 5.6% to 21.9%. Loop indices from cats with chronic bronchial disease had a mean CV between 6.6% and 28.4%. Significant differences were noted in the bronchitic cats' TBFVLs, including an increased ratio of expiratory time to inspiratory time, lower expiratory flow rates, decreased area under total and peak expiratory flow curves, and decreased tidal breathing expiratory volumes (TBEV) at 0.1 and 0.5 seconds. Selected TBFVL indices were also significantly reduced. TBFVL evaluation in the cat is easy to perform, is reproducible, and has allowed for the detection of changes during tidal breathing in cats with histories and physical findings of chronic lower airway disease.

Quantitative bacterial cultures and cytological examination of bronchoalveolar lavage specimens in dogs.

Cytology and quantitative bacterial cultures of lower respiratory tract secretions are widely used in human medicine to differentiate airway infection from simple bacterial colonization. A retrospective study was conducted to determine the usefulness of quantitative aerobic cultures and Gram stain intracellular bacteria counts from bronchoalveolar lavage (BAL) specimens in dogs in diagnosing lower respiratory tract infection (LRTI) and to determine whether chronic bronchitis is associated with marked bacterial growth in dogs. The threshold determined to define clinically relevant bacterial growth was 1.7 x 10(3) colony-forming units per milliliter of BAL fluid. We used this threshold and found that diagnostic sensitivity and specificity were 86% and 100%, respectively. With a threshold for infection of >2 intracellular bacteria observed in any of 50 fields, microscopic examination of Gram stain BAL preparations had a sensitivity of 71% and a specificity of 97% in establishing LRTI. There was a high correlation between bacterial morphology on BAL Gram stain and bacterial cultures. Combining the results of intracellular bacteria counts from the BAL Gram stain with those from the quantitative cultures, the sensitivity in diagnosing LRTI was 87% and the specificity was 97%. BAL quantitative cultures as well as quantitating intracellular bacteria on Gram stain BAL cytology were revealed to be useful in identifying LRTI in dogs. Chronic bronchitis does not appear to be associated with marked bacterial growth in dogs.

Bronchopulmonary disease in the cat: historical, physical, radiographic, clinicopathologic, and pulmonary functional evaluation of 24 affected and 15 healthy cats.

The results of clinical and pulmonary functional evaluation of 24 cats with bronchopulmonary disease and 15 healthy cats are presented. Affected cats had historical evidence of excessive reflexes (coughing, sneezing); physical evidence of airway secretions (crackles), obstruction (wheezing), and increased tracheal sensitivity; radiographic evidence of bronchial and interstitial lung disease; and cytological evidence of airway inflammation or mucous secretions. Bacterial isolates from healthy and affected cats were predominantly Gram-negative rods, indicating that bronchi of cats are not always sterile and that normal flora should be considered in interpreting cultures from cats with suspected bronchopulmonary disease. Cats were grouped according to relative disease severity based on scored historical, physical, and radiographic abnormalities. The mean (+/- standard deviation) baseline lung resistance measurement in healthy cats was 28.9 cm H2O/L/s (+/- 6.2 cm H2O/L/s), whereas in mildly, moderately, and severely affected cats it was 38.3 cm H2O/L/s (+/- 21.5 cm H2O/L/s), 44.8 cmH2O/L/s (+/- 7.7 cm H2O/L/s), and 105.2 cm H2O/L/s (+/- 66.9 cm H2O/L/s), respectively. In healthy cats, dynamic lung compliance was 19.8 (+/- 7.4), whereas in mildly, moderately, and severely affected cats it was 14.7 mL/cm H2O (+/- 3.8 mL/cm H2O), 17.7 mL/cm H2O (+/- 6.9 mL/cm H2O), and 13.0 mL/cm H2O (+/- 7.9 mL/cm H2O), respectively. Thus, airway obstruction was present in many of the affected cats. Based on acute response to the bronchodilator, terbutaline, airway obstruction was partially reversible in many affected cats, although the degree of reversibility varied. Furthermore, based on bronchoprovocation testing, 6 (of 7) affected cats evaluated also had increased airway responsiveness to aerosolized methacholine.

Systematic identification of endobronchial anatomy during bronchoscopy in the dog.

The endobronchial anatomy of 10 inflated, air-dried, canine lungs and 8 healthy anesthetized, sternally recumbent, mixed-breed dogs was evaluated, using a flexible fiberoptic bronchoscope. On the basis of the order of branching of lobar and segmental bronchi observed in these lungs, a nomenclature system was devised to systematically identify individual lobar, segmental, and subsegmental bronchi during bronchoscopy in the dog.

Pharmacokinetics of procainamide hydrochloride in dogs.

Pharmacokinetics of procainamide hydrochloride were studied in 2 groups of dogs. In a group of 6 dogs, procainamide was administered IV at a small dose of 8 mg/kg (group 1), and blood samples were obtained for 3.5 hours. In another group of 6 dogs, procainamide was administered IV and orally at an average dose of 25.5 mg/kg (group 2) in a crossover manner. Blood samples were obtained for 48 hours. In 2 dogs (previously used in part II), N-acetylprocainamide (NAPA) was administered IV at a dose of 10 mg/kg. Plasma samples were assayed for procainamide by fluorescence polarization immunoassay, and NAPA samples were assayed by high-performance liquid chromatography. In group 1, the elimination of procainamide was described by a 1-compartment, open pharmacokinetic model. The elimination half-life was 2.43 hours, the apparent volume of distribution was 1.44 L/kg, and the systemic clearance was 0.412 L/kg/hr. In group 2, 2 of the 6 dogs were described by a 1-compartment model, and 4 of the 6 dogs were described with a 2-compartment pharmacokinetic model. The elimination half-life for the IV dosage was 2.85 hours, the apparent volume of distribution was 2.13 L/kg, and the systemic clearance was 0.519 L/kg/hr. For the orally administered dose, the bioavailability was 85%, and the absorption half-life was 0.5 hours. There was no evidence of acetylation of procainamide to NAPA or deacetylation of NAPA to procainamide. The estimated elimination half-life of NAPA was 4.7 hours.

Measurement of upper airway resistance in awake untrained dolichocephalic and mesaticephalic dogs.

A technique for measuring upper airway resistance was developed in awake untrained dolichocephalic and mesaticephalic dogs. Twenty healthy dogs, 10 Collies (group A--dolichocephalic) and 10 mixed-breed dogs (group B--mesaticephalic), were studied. All dogs tolerated the procedure well, and adverse effects were not observed. Mean (+/- SEM) value for upper airway resistance was 7.1 +/- 0.50 cm of H2O/L/L/s. There was a trend toward lower upper airway resistance (R(uaw)) values in group-A dogs, compared with those in group-B dogs. Values of R(uaw) were reproducible for an individual dog. The mean individual dog coefficient of variation for R(uaw) was 7.5%. The overall R(uaw) coefficient of variation for all 20 dogs was 31.4%. This technique for measuring upper airway resistance in dogs is clinically applicable for objectively assessing response to treatment of obstructive upper airway disorders.

Thoracic bite wounds and associated internal injury in 11 dogs and 1 cat.

In 11 dogs and 1 cat with thoracic bite wounds and associated internal injury, the most common radiographic findings were subcutaneous emphysema, pulmonary infiltrates (contusion), pneumothorax, and rib separation. Treatment consisted of simple wound cleansing/repair, extensive thoracic surgery, or pleural drainage. Three of the 12 animals died or were euthanatized as a result of their bite wounds, 1 from a nonthoracic injury and 2 as a result of pleural and/or parenchymal disease.

Use of corticosteroids for treating dogs with airway obstruction secondary to hilar lymphadenopathy caused by chronic histoplasmosis: 16 cases (1979-1997).

OBJECTIVE: To examine use of corticosteroids in treating dogs with airway obstruction secondary to hilar lymphadenopathy caused by chronic histoplasmosis. DESIGN: Retrospective study. ANIMALS: 16 dogs. PROCEDURE: Records for dogs with airway obstruction examined from January 1979 through December 1997 were reviewed. Dogs were included in the study if they had hilar lymphadenopathy documented radiographically and bronchoscopically, had serum antibodies against Histoplasma capsulatum, and did not have organisms in any cytologic or histologic samples. Dogs were assigned to groups on the basis of treatment given (5 dogs, corticosteroids only; 5 dogs, corticosteroids and antifungal medication; 6 dogs, antifungal medication only). RESULTS: Clinical signs resolved in < 1 week in dogs treated only with corticosteroids. In dogs treated with corticosteroids and an antifungal medication, improvement was evident in a mean of 2.6 weeks. In 5 of 6 dogs treated with only an antifungal medication, clinical signs resolved in a mean of 8.8 weeks. Dogs receiving corticosteroids did not develop active or disseminated histoplasmosis. CLINICAL IMPLICATIONS: Corticosteroids can be used successfully in the treatment of dogs with hilar lymphadenopathy secondary to histoplasmosis. Affected dogs must be carefully evaluated for active infection. Specimens obtained by means of bronchoalveolar lavage, tracheal washing, or other methods should be examined to exclude the possibility of an active infection, which could result in corticosteroid-induced dissemination of disease.

Surgical management of atypical lateral tracheal collapse in a dog.

Tracheal collapse is often diagnosed in small-breed dogs through use of conventional radiography or fluoroscopy, by which the dorsoventral orientation of the collapse can be seen. In the dog of this report, an unusual lateral form of tracheal collapse was diagnosed by means of bronchoscopy after multiple radiographic procedures had failed to define a cause for cough and dyspnea. Surgical reinforcement of the abnormal region of the trachea resulted in resolution of clinical signs and in reduction in dynamic airway collapse, which was documented on follow-up bronchoscopy.

Endoscopically placed tubes for administration of enilconazole for treatment of nasal aspergillosis in dogs.

An endoscopic method for administering commercial-grade enilconazole for treatment of nasal aspergillosis in dogs is described. Six dogs with confirmed nasal aspergillosis were anesthetized and feeding tubes were placed endoscopically into caudal sinuses. Commercial-grade enilconazole was infused into turbinates and sinuses for a total dwell time of 45 to 60 minutes. Dogs did not have recurrence of disease at final rhinoscopic examination and were markedly improved a mean of 13.3 months after treatment.

Pulmonary lobectomy in the management of pneumonia in dogs: 59 cases (1972-1994).

OBJECTIVE: To evaluate the risk and efficacy of pulmonary lobectomy in dogs with pneumonia. DESIGN: Retrospective study. ANIMALS: 59 dogs with pneumonia. PROCEDURE: Review of medical records and telephone conversations. RESULTS: 54.2% of dogs had resolution of pneumonia after lobectomy, 20.3% died in the perioperative period, and 25.4% survived the perioperative period but pneumonia did not resolve. Pneumonia was caused by bacteria (25 dogs), fungi (12), foreign bodies (8), parasites (1), viruses (1), and allergies (1). In 11 dogs, the etiologic agent was not isolated. Bacterial or fungal pneumonias were significantly less likely to resolve compared with foreign body pneumonia or when an etiologic agent was not isolated. Perioperative mortality rate increased significantly with an increase in number of pulmonary lobes removed. Complications during surgery significantly increased perioperative mortality rate. Surgical era (1972 to 1983 vs 1984 to 1994) was a significant predictor of mortality, with the odds of dying in the perioperative period being 11 times greater between 1972 to 1983. The odds of failure to resolve pneumonia was 3 times greater during 1972 to 1983. CLINICAL IMPLICATIONS: Number of pulmonary lobes removed and complications during surgery significantly affect perioperative mortality rate. Identification of etiologic agents may help in predicting dogs likely to resolve pneumonia after surgery.

Use of an amphotericin B lipid complex for treatment of blastomycosis in dogs.

OBJECTIVE: To evaluate efficacy and nephrotoxicity of amphotericin B lipid complex used for treatment of dogs with naturally developing blastomycosis. DESIGN: Prospective clinical trial. ANIMALS: 11 dogs with blastomycosis. PROCEDURE: All dogs were treated with an amphotericin B lipid complex. Two dogs received a cumulative dose of 8 mg/kg of body weight, 1 received a cumulative dose of 10 mg/kg, and 8 received a cumulative dose of 12 mg/kg. RESULTS: The 2 dogs that received a cumulative dose of 8 mg/kg and 1 of the dogs that received a cumulative dose of 12 mg/kg had a relapse of blastomycosis within 30 days after treatment. Seven of the remaining 8 dogs were clinically free of blastomycosis 6 months after treatment. One dog died of an unrelated cause 5.5 months after treatment, but did not have clinical signs of blastomycosis at the time of death. There were not any adverse clinical effects attributable to drug administration in any of the dogs in this study, and none of the dogs developed clinical signs of renal disease or failure. CLINICAL IMPLICATIONS: Amphotericin B lipid complex was a safe and effective treatment for blastomycosis in these dogs.

Nonenteric Escherichia coli isolates from dogs: 674 cases (1990-1998).

OBJECTIVE: To determine nonenteric sites associated with Escherichia coli isolates in dogs and the antimicrobial susceptibilities of the isolates. DESIGN: Retrospective study. SAMPLE POPULATION: 17,000 canine specimens. PROCEDURE: Medical records of 17,000 canine specimens submitted for bacteriologic culture were examined and the number of isolations of E coli was determined. For these cases, records were further examined with respect to body system involvement, sex, concurrent infection with other species of bacteria, and antimicrobial susceptibility. RESULTS: 674 E coli isolates (424 from urine, 62 from the skin, 52 from the respiratory tract, 45 from the ear, 43 from the female reproductive tract, 25 from the male reproductive tract, and 23 from other organ systems) were identified. There was a significantly higher proportion of isolates from urine specimens from spayed females than from sexually intact females or males. Escherichia coli was isolated in pure culture from 65.9% of the specimens. Most E coli isolates were susceptible to norfloxacin (90%), enrofloxacin (87.5%), gentamicin (90.7%), and amikacin (85.9%). CONCLUSIONS AND CLINICAL RELEVANCE: Most nonenteric E coli infections in dogs involve the urinary tract. Amikacin, gentamicin, norfloxacin, and enrofloxacin have the highest efficacy against canine E coli isolates. For E coli isolates from dogs, in vitro susceptibility to commonly used antimicrobial agents has remained fairly stable during the past decade.

Diagnosis and treatment of canine chronic bronchitis. Twenty years of experience.

Chronic bronchitis is a frustrating disease because the cause is rarely determined, the pathologic changes that accompany and define the disease are usually nonreversible and often progress to life-threatening disorders, and there is a lack of direct scientific evidence for the treatment recommendations that have been offered for the management of this disease in dogs. This article reviews the pathophysiology, clinical presentation, diagnosis, and evaluation of chronic bronchitis in dogs. Important diagnostic tools for use in diagnosis are discussed, including clinical pathology, chest radiographs, and culture and cytology of airway fluid samples.

Clinical pulmonary function testing in dogs and cats.

Pulmonary function testing is a relatively new area in clinical veterinary medicine, with few individuals currently obtaining TBFVL and pulmonary mechanics on a clinical cases of respiratory disease in dogs and cats. ABG analysis is a technique available to all veterinarians through commercial laboratories or local hospitals. Information obtained from these tests will allow for a better understanding of the pathophysiology of naturally occurring diseases as well as assisting in the determination of the efficacy of various therapeutic agents (such as bronchodilators), which to date has been lacking in veterinary medicine.

Respiratory therapeutics.

Treatment of small animal respiratory diseases tends to target bronchodilators. Although this is not inappropriate, recent advances in the understanding of respiratory diseases have underscored the importance of inflammatory mediators in the pathophysiology of respiratory diseases. Drug therapy of the respiratory tract in small animals is most successful when it is based on a knowledge of normal physiology and disease pathophysiology of respiratory tract diseases.

Pathogenesis and treatment of canine rhinitis.

Unless a systematic approach is used, evaluation of a patient with rhinitis can be frustrating to the veterinary practitioner. A complete differential list for canine rhinitis should include infectious, inflammatory, neoplastic, and traumatic causes. Other causes of rhinitis include dental disease, parasitic infestation, and ciliary dyskinesia. Diagnostic techniques that should be considered when evaluating a patient with rhinitis include obtaining a complete history, performing a thorough physical and oral examination, evaluating the patient's coagulation abilities, cytology and culture of exudate, nasal radiographs, and rhinoscopy. This article describes the pathogenesis and treatment of the various causes of canine rhinitis.