bluuebunny/crossref_metadata_2025 huggingface dataset:
Population pharmacokinetics of gentamicin in horses
Authors: Martín-Jiménez Tomás , Papich Mark G. , Riviere Jim E.
Published: January 2024

Objective

To develop and validate a population pharmacokinetic model for gentamicin in horses, using retrospective clinical data.

Animals

62 horses that had been treated IV with multiple doses of gentamicin at our veterinary teaching hospital between 1987 and 1996.

Procedure

46 horses were assigned to the study group, and 16 to the validation group. Detailed history of dosage, sample collection times, and selected pathophysiologic variables were recorded for each patient. Samples were analyzed by use of a fluorescence polarization immunoassay method. Pharm-acostatistical analysis was conducted, using computer software. The predictive model correlates pharmacokinetic parameters to concomitant pathophysiologic variables and estimates the inter- and intraindividual variability in disposition.

Results

A two-compartment model best described the data. Clearance (Cl) was linearly correlated to body weight and serum creatinine concentration. Volume of the central compartment (Vdc) was linearly related to body weight. Interindividual coefficients of variability for Cl and Vdc were 24 and 16%, respectively. The residual variability (intraindividual) was 13%; mean prediction error percent (bias) was 2%; and mean absolute prediction error percent (precision) was 29%.

Conclusions

Population pharmacokinetic analysis allows study of the basic features of gentamicin disposition in horses with sparse data per individual. A considerable proportion of the pharmacokinetic variability of gentamicin in our study population was explained by differences in body weight and serum creatinine concentration.

Clinical Relevance

Population pharmacokinetics can be used to design first-dosage regimens according to the clinical characteristics of individual animals. Population pharmacokinetic models could also be included in Bayesian forecasting strategies to improve plasma concentration predictions in individual patients. (Am J Vet Res 1998;59:1589-1598)
Analysis of coagulation proteins as acute-phase reactants in horses with colic
Authors: Topper Michael J. , Prasse Keith W.
Published: January 2024

Objectives

To measure coagulation factor VIII:coagulant (F.VIII:C) and C1-esterase inhibitor (C1-INH), hemostasis-associated acute-phase reactant proteins, and coagulation factors VII (F.VII), IX (F.IX), and X (F.X), hemostasis proteins not associated with an acute-phase response, in a select population of horses with colic and hemostasis abnormalities, and presumed to have acute-phase changes. To compare these values and other routine hemostasis test results in the horses with colic with values for a population of healthy horses. To correlate the values of known equine acute-phase reactants, F.VIII:C and fibrinogen, to those of other tests of hemostasis. To identify hemostasis-associated acute-phase reactant proteins and gain insights into the effects the acute-phase response has on hemostatic abnormalities in horses with colic syndrome.

Sample Population

54 plasma samples from horses with colic attributable to inflammatory (n = 39) or strangulating (n = 15) intestinal disorders.

Procedure

Plasma samples were evaluated for activities of F.VII, F.VIII:C, F.IX, F.X, C1-INH, antithrombin III, protein C, plasminogen, and α2-antiplasmin (α2AP); fibrinogen concentration; and prothrombin (PT) and activated partial thromboplastin (APTT) times.

Results

Horses with colic had significantly higher fibrinogen concentration, greater α2AP and protein C activities, and longer PT and APTT than did healthy horses. Horses with colic also had significantly lower mean F.VII activity than did healthy horses. Significant positive correlations between fibrinogen concentration and F.VIII:C, C1-INH, and α2AP values, and between F.VIII:C activity and fibrinogen, C1-INH, α2AP, and plasminogen values were identified.

Conclusions

An acute-phase response contributes to changes observed in coagulation proteins in horses with colic attributable to inflammatory and strangulating intestinal disorders. The data suggest that plasminogen, α2AP, and C1-INH should be considered equine acute-phase proteins. (Am J Vet Res 1998;59:542–545)
Immunohistochemical characterization of immunoglobulin-containing cells and T cells in the colonic mucosa of healthy dogs
Authors: Jergens Albert E. , Gamet Yvan , Niyo Yosiya , Bailey Theodore B. , Brabec Marek , Smith Becky
Published: January 2024

Objectives

To quantitate numbers of immunoglobulin (Ig)-containing cells (IgA, IgG, and IgM) and T cells (CD3+, CD4+, and CD8+) in the colonic mucosa of healthy dogs, and to determine whether mean cell numbers differ among colonic regions.

Animals

10 clinically normal young adult mixed-breed dogs.

Procedure

Endoscopically obtained specimens of ascending, transverse, and descending colonic mucosa were stained specifically for IgA, IgG, and IgM heavy chains and T-cell antigens, CD3+, CD4+, and CD8+, using immunoperoxidase techniques. Morphometric analysis, performed by light microscopy, was used to quantitate numbers in these standardized areas of colonic mucosa. Data analysis allowed determination of mean cell numbers in each colonic region, as well as comparison of mean cell numbers among colonic regions.

Results

The CD3+ and CD8+ T cells were the predominant immune cell types in all colonic regions. In the mucosa, CD3+ T cells were significantly (P < 0.05) more numerous than CD8+ T cells, and CD8+ T cells were significantly (P < 0.05) more numerous than CD4+ T cells. The IgA-containing cells were significantly (P < 0.05) more numerous than IgG-containing cells, whereas IgM-containing cells were least numerous (P < 0.05). Differences in mean cell counts among colonic regions were not significant for Ig-containing cells or T cells.

Conclusions

Mean numbers of immune cells did not differ significantly among colonic regions in healthy dogs, although differences existed in mean populations of T cells and Ig-containing cells. The CD3+ and CD8+ T cells were the most numerous immune cell types in colonic mucosa.

Clinical Relevance

These quantitative data provide a basis for study of alterations in populations of mucosal immune cells and their possible contribution to the pathogenesis of gastrointestinal tract disease. (Am J Vet Res 1998;59:552–556)
Development and use of an enzyme-linked immunosorbent assay to monitor serum and urine acepromazine concentrations in Thoroghbreds, and possible changes associated with exercise
Authors: Chou Chi-Chung , Chen Chao-Ling , Asbury Atwood C. , Webb Alistair I. , Vickroy Thomas W.
Published: January 2024

Objectives

To develop an ELISA that is sensitive and suitable for measurement of immunoreactive acepromazine (ACP) in horse serum and urine and to determine the acute effects of exercise on immunoreactive ACP values in Thoroughbreds.

Animals

12 healthy Thoroughbreds (5 mares, 5 geldings, 2 stallions), aged 2 to 8 years.

Procedure

A commercially available antibody and a horseradish peroxidase-conjugated oxime derivative of immunoreactive ACP were used to develop a one-step ELISA. Horses were used in a crossover design study to evaluate possible effects of treadmill exercise on serum and urine ACP concentrations after a single (25 mg) IM injection of the drug.

Results

Immunoreactive ACP was detectable at concentrations as low as 50 pg/ml in serum and 100 pg/ml in urine, with intra- and interassay variabilities of 1.1 and 5.2%, respectively. The antibody had some cross-reactivity with a limited number of other phenothiazines. After drug administration, serum ACP immunoreactivity achieved a peak concentration (10.5 ng/ml) within 30 minutes and could be measured up to 48 hours in serum and 120 hours in urine. Although exercise had no significant effect on serum drug concentration, immunoreactive ACP disappeared more quickly (by 48 hours) from the urine of horses in the exercised group.

Conclusions

This one-step ELISA provides a simple and sensitive means to measure immunoreactive ACP in equine serum and urine. The ability to detect drug several days after administration of a low dose of ACP should augment efforts to control illicit use of this drug in performance horses. Potential changes in ACP kinetics after exercise warrant further study. (Am J Vet Res 1998;59:593–597)
Effect of xylazine, detomidine, and a combination of xylazine and butorphanol on equine duodenal motility
Authors: Merritt A. M. , Burrow J. A. , Hartless C. S.
Published: January 2024

Objective

To evaluate the effect on equine duodenal motility of some analgesic agents commonly used to treat colic.

Animals

4 healthy adult healthy horses—2 mares and 2 geldings—which were carrying an indwelling gastric cannula made of silastic rubber. One horse also carried 2 long-term indwelling bipolar electrodes that had been sutured onto the duodenum and jejunum.

Procedure

To ensure an empty stomach, solid food was withheld from horses for around 20 hours prior to an experiment. Using videoendoscopic guidance, an 8-F catheter with 3 small, discrete pressure sensors was passed through the gastric cannula and directed into the proximal portion of the duodenum. Deflection of the recording pen, to which the catheter was attached, indicated a motile event in that section. Drugs (treatment) were given into the jugular vein in a randomized block design, 1 treatment/experiment, after a 1-hour baseline recording. Treatments were: 2 ml of 0.9% NaCl, xylazine (XYL, 0.5 mg/kg of body weight), detomidine (DET, 0.0125 mg/kg), or a xylazine/butorphanol combination (XYB, 0.5/0.05 mg/kg). Each horse received each treatment twice. All positive pressure peaks > 5 mm of Hg recorded from the most proximal sensor on the catheter were counted in 15-minute blocks. Each mean 15-minute posttreatment value was compared with the baseline value for that specific treatment.

Results

There was no significant difference between baseline values. All treatments significantly (P < 0.05) reduced frequency of pressure peaks below their respective pretreatment values, but to variable degrees and durations. Comparatively, XYL had the least effect, with mild, though significant, reduction for only the first 30 posttreatment minutes; DET and XYB caused a significant marked reduction for 1 hour after treatment.

Conclusions

The profound suppressive effect of a routine dose of detomidine or xylazine/butorphanol combination on equine duodenal motility must be considered when using these agents for management of colic, especially when encouragement of intestinal motility is desirable. (Am J Vet Res 1998;59:619–623)
Relation between pathologic findings and cellular immune responses in sheep with naturally acquired paratuberculosis
Authors: Pérez V. , Tellechea J. , Corpa J. M. , Gutiérrez M. , Marín J. F. García
Published: January 2024

Objective

To investigate the relation between lesions and cellular immune response-based tests in sheep with naturally acquired paratuberculosis and to evaluate efficacy of an interferon-γ (IFN-γ) assay and the intradermal skin test.

Animals

110 and 88 adult sheep were used to evaluate the IFN-γ assay and skin test, respectively.

Procedure

Before euthanasia, heparinized blood was collected and incubated with avian purified protein derivative (PPD). Interferon-γ production was assessed, using a commercial enzyme immunoassay. Skin testing in the caudal fold also was performed, using avian PPD. Sensitivity and specificity of these techniques were evaluated, using histopathologic findings as reference.

Results

Of the sheep examined, 61 (55.4%) had lesions that were classified in 5 categories, according to location, extension, cellular types, and presence of acid-fast bacilli. Regarding cellular immunity test results, 55.4% of sheep with and 6.1% without pathologic changes had positive results of the IFN-γ assay. Skin test sensitivity (55.6%) and specificity (100%) were slightly greater.

Conclusion

Close association between pathologic findings and cellular immune response was apparent. Most sheep with focal (tuberculoid) and some with diffuse lesions (borderline tuberculoid), all with scant or no acid-fast bacilli in the intestine, had positive results of the IFN-γ assay and skin test. Most sheep with diffuse lesions and high numbers of bacilli (borderline lepromatous) were test negative.

Clinical Relevance

Cellular immune response-based and serologic tests are useful tools for seeking evidence of paratuberculosis. Each technique detects different types of immune-reacting sheep, and their simultaneous use may detect most infected animals. (Am J Vet Res 1999;60:123–127)
Potential for contact and mechanical vector transmission of vesicular stomatitis virus New Jersey in pigs
Authors: Stallknecht D. E. , Howerth E. W. , Reeves C. L. , Seal B. S.
Published: January 2024

Objective

To determine whether swine could be infected with vesicular stomatitis virus New Jersey (VSV-NJ) by routes simulating mechanical vector and contact transmission, and to document clinical response and measure source, duration, and extent of associated viral shedding.

Animals

48 approximately 10-kg male pigs.

Procedure

7 inoculation routes were tested at 3 virus concentrations (106, 104, and 102 median tissue culture-infective doses [TCID50]). Inoculation routes included intradermal (snout), topical application of virus to a scarified area (ear or mucous membrane of the lip), mucosal (oral or conjunctiva) application, and nasal instillation (drop or aerosol). Swine were monitored daily for clinical disease, seroconversion, and virus isolation.

Results

Virus was isolated from swab specimens of nasal planum, nasal cavity, saliva, tonsil, and feces from 15 pigs infected by intradermal snout inoculation (106 and 104 TCID50), scarification of the lip (106 and 104 TCID50), and oral route (106 TCID50). Virus was not isolated from plasma. Vesicular lesions were restricted to pigs inoculated via intradermal snout and lip scarification routes. Seroconversion was detected in 23 pigs inoculated by all routes except intranasal aerosol and conjunctival. Frequency of virus isolation from these pigs was dependent on serologic status and presence of vesicular lesions.

Conclusions

Viral titers obtained from swab specimens and infective doses indicated that sufficient virus is shed from infected swine for contact or mechanical transmission to occur. Amount of virus is highest when lesions are present and before seroconversion. Pigs may represent an effective large-animal model for studying pathogenesis and transmission of VSV-NJ. (Am J Vet Res 1999;60: 43–48)
Influence of sex and age on serum total immunoglobulin E concentration in Beagles
Authors: Racine Brigitte P. , Marti Eliane , Busato André , Weilenmann Richard , Lazary Sandor , Griot-Wenk Monika E.
Published: January 2024

Objective

To establish an ELISA for detection of serum total IgE concentration in dogs and to analyze IgE values in a dog colony.

Animals

147 healthy Beagles (31 males and 116 females).

Procedure

2 canine IgE-specific polyclonal antibodies elicited by 2 recombinant fragments of the epsilon chain in hens were used to develop a capture ELISA specific for serum total IgE concentration. The IgE values were calculated by comparing serum dose-response curves (1:50 to 1:6,400) with a reference serum pool assigned 100 relative ELISA units (REU).

Results

Mean IgE concentration in female Beagles was 51.2 REU (range, 0 to 337.8 REU; median, 31.4 REU), whereas mean IgE concentration in male dogs was only 7.5 REU (range, 0 to 32.6 REU; mean, 3.6 REU). Distribution of IgE values was skewed; approximately 80% of dogs had IgE values < 50 REU. Analysis of natural logarithmically transformed IgE values indicated that sex and age significantly (P < 0.05) influenced IgE values; mean serum IgE values increased until the age of 4 years. Heritability estimates of IgE concentration indicated a trend toward a genetic influence.

Conclusion

A reliable capture ELISA specific for canine IgE was developed. Serum total IgE values vary with age and sex in the sample population.

Clinical Relevance

Serum total IgE concentration can now be evaluated in various dog breeds and, subsequently, in dogs with IgE-mediated diseases provided that these significant influences are accounted for. Serum total IgE values may then prove to be of diagnostic value, similar to their use in human beings. (Am J Vet Res 1999;60:93–97)
Pathologic changes in the lumbosacral vertebrae and pelvis in Thoroughbred racehorses
Authors: Haussler Kevin K. , Stover Susan M. , Willits Neil H.
Published: January 2024

Objective

To describe the prevalence, characteristics, and severity of soft-tissue and osseous lesions in the caudal portion of the thoracic and lumbosacral vertebral column and pelvis in Thoroughbred racehorses.

Animals

36 Thoroughbred racehorses that died or were euthanatized at California racetracks between October 1993 and July 1994.

Procedure

Lumbosacral and pelvic specimens were collected and visually examined for soft-tissue and osseous lesions.

Results

Acute sacroiliac joint injury was observed in 2 specimens. Signs of chronic laxity or subluxation of the sacroiliac joint were not observed in any specimens. Impingement of the dorsal spinous processes and transverse processes was observed in 92 and 97% of specimens, respectively. Thoracolumbar articular processes had variable degrees of degenerative change in 97% of specimens. Degenerative changes were observed at lumbar intertransverse joints and sacroiliac articulations in all specimens. Some degenerative changes were widespread and severe.

Conclusions

Numerous degenerative changes affected vertebral processes, intervertebral articulations, and sacroiliac joints in these Thoroughbred racehorses.

Clinical Relevance

Various types of vertebral and pelvic lesions need to be considered during clinical evaluation of the back and pelvis in horses. Undiagnosed vertebral or pelvic lesions could be an important contributor to poor performance and lameness in athletic horses. (Am J Vet Res 1999:60:143-153).
In vitro response of large colon arterial and venous rings to vasodilating drugs in horses
Authors: Sedrish Steven A. , Venugopalan Changaram S. , Holmes Earnestine P. , Koch Catherine E. , Moore Rustin M.
Published: January 2024

Objective

To determine in vitro vasomotor response of equine large colon arterial and venous rings with and without endothelium to vasodilator drugs, including dopamine (DOP), dopexamine (DPX), acepromazine (ACE), isoxsuprine (ISX), and nifedipine (NFP).

Animals

7 adult horses.

Procedure

Relaxation of large colon arteries and veins in response to vasodilating drugs was determined by measuring the change in tension of vessel rings when exposed to a cumulative concentration range (10−8 to 10−4 M) of each drug. Vessel rings, with and without endothelium, were mounted in organ baths, attached to a transducer, and contracted with norepinephrine (NE). Cumulative concentration-response relationships, percentage maximal relaxation, and EC50 (concentration of drug required to relax the NE-induced contracted tissue to 50% of its contracted state) values were calculated.

Results

There were significant differences among drugs for EC50 (ACE = ISX < NFP) and percentage maximal relaxation (ACE = ISX > NFP = DPX > DOP) values in veins. Endothelium removal from veins had no significant effect. There were no differences in EC50 values for arteries; however, percentage maximal relaxation was significantly different among drugs (ACE = ISX = NFP > DPX = DOP). Endothelial removal resulted in higher EC50 and lower percentage maximal relaxation values, compared with endothelium-intact arteries.

Conclusion and Clinical Relevance

ACE and ISX were the most potent and efficacious drugs evaluated and could potentially be used to improve blood flow after correction of large-colon volvulus. Dopamine cannot be recommended because of its biphasic response and potential to further decrease blood flow. Endothelium removal altered the vasodilatory responses of colonic arterial rings, but did not affect venous rings. (Am J Vet Res 1999;60: 204-210)
Role of platelet activating factor in development of thrombocytopenia and neutropenia in dogs with endotoxemia
Authors: Tsuchiya Ryo , Kyotani Kazumi , Scott Michael A. , Nishizono Kazuya , Ashida Yoshinori , Mochizuki Toshihiko , Kitao Satoshi , Yamada Takatsugu , Kobayashi Kousaku
Published: January 2024

Objective

To determine the role of platelet activating factor (PAF) in lipopolysaccharide (LPS)-induced thrombocytopenia and neutropenia in dogs.

Animals

42 dogs.

Procedures

Blood samples were obtained from dogs given LPS (40 µg/kg of body weight; n = 16), PAF (1 µg/kg; 6), PAF (5 µg/kg/h for 90 minutes; 4), or physiologic saline (0.9% NaCl) solution (0.1 ml/kg/h for 90 minutes; 3) IV to monitor changes in blood cell counts, using automated counters and blood smears stained with Giemsa. Blood samples were also obtained from dogs given LPS (40 µg/kg) that had (n = 5) or had not (6) been treated beforehand with TCV-309, a potent PAF antagonist. Concentration of PAF in blood was determined by use of 125I-radioimmunoassay in dogs given LPS at 1 mg/kg (n = 3) and 40 µg/kg (9).

Results

Thrombocytopenia and neutropenia were found in all dogs except those given saline solution. The LPS-induced thrombocytopenia was significantly suppressed by prior treatment with TCV-309. The PAF concentrations increased markedly 1 hour after injection of 1 mg/kg of LPS and increased slightly but significantly 10 minutes after injection of 40 µg/kg of LPS.

Conclusion and Clinical Relevance

PAF plays an important role in the development of LPS-induced thrombocytopenia and neutropenia in dogs. Control of PAF production, PAF-induced effects, or both may be important in the treatment of dogs with gram-negative bacterial infections and associated thrombocytopenia and neutropenia. (Am J Vet Res 1999;60; 216-221)
Effects of sample storage and delayed secondary enrichment on detection of Salmonella spp in swine feces
Authors: O'Carroll Julia M. , Davies Peter R. , Correa Maria T. , Slenning Barrett D.
Published: January 2024

Objective

To determine effects of fecal sample storage and delayed secondary enrichment (DSE) on detection of Salmonella spp in swine feces.

Sample Population

Fecal samples obtained from 84 pigs in a commercial herd.

Procedure

Each fecal sample underwent 3 storage treatments: no storage (ie, processed on the day of collection), storage at 4 C for 6 days, and storage at −15 C for 14 days. After assigned storage treatments, all samples were enriched in Rappaport-Vassiladias (RV) broth (single enrichment) and plated on XLT4 agar. Delayed secondary enrichment was performed, using single enrichment broths that were stored for 4 days at room temperature.

Results

Of 504 cultures, 186 (36.9%) were Salmonella positive. A difference in proportions of samples with positive results was not found between same-day processing and storage at 4 C for 6 days. Compared with use of single enrichment for 24 hours (34% positive), use of DSE resulted in a greater proportion (40%; P < 0.001) of samples with positive results. Estimated relative sensitivities for the storage methods were 0.90, 0.85, and 0.71 for same-day processing, storage at 4 C for 6 days, and storage at −15 C for 14 days, respectively.

Conclusions

Where practical, processing of fecal samples on the day of collection is recommended, although storage at 4 C for several days does not result in marked loss of sensitivity. Improved detection associated with DSE warrants further investigation and optimization. (Am J Vet Res 1999;60:359–362)
Changes in cortisol concentration in response to stress and postoperative pain in client-owned cats and correlation with objective clinical variables
Authors: Smith Julie D. , Allen Sheila W. , Quandt Jane E.
Published: January 2024

Objective

To identify clinical variables that indicate postoperative pain in cats after ovariohysterectomy in a veterinary hospital setting.

Animals

40 cats.

Procedure

Cats were anesthetized and ovariohysterectomized by senior veterinary students. Butorphanol (0.1 mg/kg [n = 20] or 0.3 mg/kg [20] of body weight) was administered IM after surgery. Blood samples were obtained before, during, and after the anesthestic period for measurements of PCV and blood glucose and cortisol concentrations. Clinical variables measured included heart rate, systolic blood pressure, respiratory rate, and rectal temperature. Data for these variables were compared with changes in cortisol concentrations and with similar data—which was used as historical control data— obtained from 20 cats in another study (10 that had been ovariohysterectomized but had not received butorphanol and 10 that had only been anesthetized).

Results

Surgical durations were longer in this study, and cats had higher cortisol concentrations, compared with historical control cats. Objective clinical variables did not consistently correlate with changes in cortisol concentration.

Conclusions

Cortisol concentration increased in response to surgical stress and pain. This response was greater in cats in which duration of surgery was longer.

Clinical Relevance

The objective clinical variables evaluated in this study were not consistent indicators of pain in an uncontrolled, clinical situation. (Am J Vet Res 1999;60:432-436)
Glucose uptake in horses with polysaccharide storage myopathy
Authors: De La Corte Flavio D. , Valberg Stephanie J. , MacLeay Jennifer M. , Williamson Sarah E. , Mickelson James R.
Published: January 2024

Objective

To determine whether excessive glycogen accumulation in skeletal muscle of Quarter Horses with polysaccharide storage myopathy (PSSM) is a result of enhanced cellular uptake of glucose.

Animals

6 horses with PSSM and 10 healthy (control) horses.

Procedure

Intravenous glucose tolerance tests (IVGTT), oral glucose tolerance tests (OGTT), and modified insulin tolerance tests (MITT) were performed. Plasma glucose and insulin concentrations were measured in blood samples collected before and for up to 8 hours after glucose or insulin administration.

Results

Peak glucose concentrations during IVGTT were similar for both groups of horses, but rate of glucose clearance was 1.5 times faster in horses with PSSM than in controls. Moreover, circulating concentrations of insulin before and after glucose injection were lower in the PSSM group. Blood glucose concentrations from minute 90 to minute 300 of the OGTT were lower in horses with PSSM than in controls. The MITT resulted in acute decreases in blood glucose concentrations in both groups of horses; however, horses with PSSM sustained low blood glucose concentrations for more than 3 hours after insulin injection, whereas blood glucose concentrations in controls returned to baseline values within 2 hours.

Conclusions

Quarter Horses with PSSM have enhanced cellular uptake of glucose that may be, in part, caused by an increased sensitivity to insulin.

Clinical Relevance

Horses with PSSM have an increased rate of glucose clearance in response to insulin secretion. Thus, diets low in soluble carbohydrate may be the most effective way to decrease glycogen accumulation in skeletal muscle of these horses. (Am J Vet Res 1999;60:458-462)
Morphologic, cytochemical staining, and ultrastructural characteristics of blood cells from eastern diamondback rattlesnakes (Crotalus adamanteus)
Authors: Alleman A. Rick , Jacobson Elliot R. , Raskin Rose E.
Published: January 2024

Objective

To evaluate light microscopic, cytochemical, and ultrastructural characteristics of blood cells from eastern diamondback rattlesnakes.

Animals

10 healthy snakes.

Procedure

Various stains, including Wright-Giemsa, benzidine peroxidase, Sudan black B, chloroacetate esterase, α-naphthyl butyrate esterase, acid phosphatase, leukocyte alkaline phosphatase, periodic acid-Schiff with diastase, and toluidine blue, were used to stain leukocytes differentially on multiple blood smears. Electron microscopy also was performed.

Results

Lymphocytes were the most commonly observed leukocyte and could be distinguished from thrombocytes, using periodic acid-Schiff stain with diastase. Azurophils also were commonly observed; their granules stained with peroxidase. Eosinophils were not identified; however, 2 morphologic variations of heterophils were seen in the blood of all snakes and were considered the same cell type at different stages of cytoplasmic granule development. Heterophil granules were better preserved, using a one-step Wright-Giemsa method that did not require alcohol fixation prior to staining. Degranulated heterophils were observed in all preparations.

Conclusions

Most leukocytes of eastern diamond-back rattlesnakes can be identified easily on Wright-Giemsa-stained preparations. However, hematologic stains that do not require alcohol fixing prior to staining may be preferred for leukocyte evaluation in certain reptiles. A limited degree of heterophil maturation may continue in the blood of healthy snakes. This, along with degranulation of heterophils, may result in a variable staining pattern in this cell type, regardless of the stain used.

Clinical Relevance

Results provide baseline data for use in hematologic testing in diagnosis of disease and monitoring of treatment of sick or injured snakes. (Am J Vet Res 1999;60:507-514)
Effects of the α-glucosidase inhibitor acarbose on postprandial serum glucose and insulin concentrations in healthy dogs
Authors: Robertson Jane , Nelson Richard , Kass Philip , Neal Larry
Published: January 2024

Objective

To determine effects of acarbose on baseline and postprandial serum glucose and insulin concentrations in healthy dogs, if effects of acarbose were dosage related, and if acarbose caused any short-term adverse effects.

Animals

5 healthy dogs fed a high-fiber diet.

Procedure

A Latin-square design was used. During each 1-week treatment period, dogs were given a placebo or 25, 50, 100, or 200 mg of acarbose, PO, twice daily immediately prior to feeding. There was a 1-week interval between periods. At the end of each treatment period, serum glucose and insulin concentrations were measured prior to feeding and at 30- to 60-minute intervals for 6 hours after feeding.

Results

Baseline serum glucose and insulin concentrations, insulin peak response, and total glucose absorption were not significantly different following treatment with placebo and treatment with acarbose; however, total insulin secretion was significantly decreased when dogs were treated with 100 or 200 mg of acarbose. Four dogs developed soft to watery stools when treated with 200 mg of acarbose, and 2 dogs lost weight during the study. Results of CBC and serum biochemical analyses were within reference ranges throughout the study.

Conclusions

Acarbose did not induce any serious adverse effects and was effective in healthy dogs in reducing total postprandial insulin secretion when administered immediately prior to meals.

Clinical Relevance

Results suggest that acarbose may help control hyperglycemia in dogs with insulin-dependent diabetes mellitus. Additional studies designed to evaluate the effect of acarbose on postprandial blood glucose concentrations in dogs with diabetes mellitus are indicated. (Am J Vet Res 1999;60:541–545)
Validation of a finite element model of the Kirschner-Ehmer external skeletal fixation system
Authors: Cross Alan R. , Aron Dennis N. , Budsberg Steven C. , Foutz Timothy L. , Pearman Brent T. , Evans Mark D.
Published: January 2024

Objective

To determine the validity of finite element analysis (FEA) as a means of examining biomechanical properties of the Kirschner-Ehmer external skeletal fixation system.

Sample Population

10 paired tibiae harvested from skeletally mature dogs weighing between 30 and 38 kg immediately following euthanasia for reasons unrelated to musculoskeletal disease.

Procedure

A gap fracture was created in each bone; fragments were stabilized with 3 frame configurations (type I, type II, and type III), using enhanced-profile threaded pins. Each bone-frame construct was tested, using a materials testing machine in 3 modes of testing: axial compression (AC), mediolateral (ML) bending, and craniocaudal (CC) bending, for a total of 9 tests/bone. The elastic limit of the constructs was not exceeded during testing. Mean stiffness values were determined from load-displacement curves. A finite element model of each construct was created, using three-dimensional elastic beam elements, and stiffness values were calculated, using FEA. Correlations between experimental and FEA data then were determined.

Results

Significant differences in stiffness were seen among all 3 constructs in CC bending and AC, with stiffness increasing with construct complexity. No significant difference in ML bending stiffness was seen between type-II and type-III constructs; however, both were significantly stiffer than the type-I constructs. The experimental and FEA stiffness data were strongly correlated (AC, r = 0.994; ML bending, r = 0.998; CC bending, r = 0.985).

Conclusions and Clinical Relevance

Strong correlations among experimental and FEA data indicate that FEA is a valid method of comparing stiffness of Kirschner-Ehmer external skeletal fixation constructs. (Am J Vet Res 1999;60:615–620)
Influence of sotalol on the time constant of isovolumic left ventricular relaxation in anesthetized dogs
Authors: Seidler Randolph W. , Mueller Klaus , Nakayama Tomohiro , Hamlin Robert L.
Published: January 2024

Objective

To determine the effects of various doses of sotalol on myocardial relaxation in healthy dogs.

Animals

12 healthy adult mixed-breed dogs anesthetized with thiopental and α-chloralose.

Procedures

Left ventricular pressure (LVP), aortic pressure, and aortic flow velocity were measured. The time constant of isovolumic relaxation (τ) was determined by means of linear regression of the natural logarithm of LVP and by means of direct measurement from the LVP-versus-time curve. Sotalol was administered IV at cumulative doses of 1, 2, 4, and 8 mg/kg to 6 dogs; the other 6 were used as controls. Mean systolic aortic pressure was used to assess afterload, and maximal rate of increase in LVP versus time (dP/dt) was used as an index of contractility.

Results

After administration of the first dose of sotalol, τ was increased significantly, and maximum dP/dt was decreased significantly, compared with baseline values. Administration of additional doses of sotalol did not result in any additional change in τ, but maximum dP/dt increased, and maximum dP/dt after administration of the final dose of sotalol was significantly higher than maximum dP/dt after administration of the first dose. There were no significant changes in mean systolic aortic pressure.

Conclusions and Clinical Relevance

In healthy dogs, sotalol did not have any negative effect on myocardial relaxation beyond those attributable to its β-blocking properties, despite an increase in intracellular ionized calcium concentration, as suggested by an increase in maximum dP/dt after an initial decrease. (Am J Vet Res 1999;60:717-721)
Pharmacokinetics of the antihyperglycemic agent metformin in cats
Authors: Michels Gina M. , Boudinot F. Douglas , Ferguson Duncan C. , Hoenig Margarethe
Published: January 2024

Objective

To determine the pharmacokinetics of metformin in healthy cats after single-dose IV and oral administration of the drug.

Animals

6 healthy adult ovariohysterectomized cats.

Procedure

In a randomized cross-over design study, each cat was given 25 mg of metformin/kg of body weight, IV and orally. Blood and urine samples were collected after drug administration, and concentrations of metformin in plasma and urine were determined by use of high-performance liquid chromatography.

Results

Disposition of the drug was characterized by a three-compartment model with a terminal phase half-life of (mean ± SD) 11.5 ± 4.2 hours. Metformin was distributed to a small central compartment of 0.057 ± 0.017 L/kg and to 2 peripheral compartments with volumes of distribution of 0.12 ± 0.02 and 0.37 ± 0.38 L/kg. Steady-state volume of distribution was 0.55 ± 0.38 L/kg. After IV administration, 84 ± 14% of the dose was excreted unchanged in urine, with renal clearance of 0.13 ± 0.03 L/h/kg; nonrenal clearance was negligible (0.02 ± 0.02 L/kg). Mean bioavailability of orally administered metformin was 48%.

Conclusions

The general disposition pattern of metformin in cats is similar to that reported for humans. Metformin was eliminated principally by renal clearance; therefore, this drug should not be used in cats with substantial renal dysfunction.

Clinical Relevance

On the basis of our results, computer simulations indicate that 2 mg of metformin/kg administered orally every 12 hours to cats will yield plasma concentrations documented to be effective in humans. (Am J Vet Res 1999;60:738–742)
Urinary orotic acid-to-creatinine ratios in cats with hepatic lipidosis
Authors: VanSteenhouse Jan L. , Dimski Donna S. , Swenson David H. , Taboada Joseph
Published: January 2024

Objective

To determine urinary orotic acid (OA) conentration and evaluate the urinary OA-to-creatinine ratio (OACR) in cats with hepatic lipidosis (HL).

Animals

20 cats with HL and 20 clinically normal cats.

Procedure

Hepatic lipidosis was diagnosed on the basis of clinical signs, results of serum biochemical analyses, exclusion of other concurrent illness, and cytologic or histologic evaluation of liver biopsy specimens. Urine samples were collected from each cat and frozen at −20 C until assayed. Urine creatinine concentrations were determined, using an alkaline picrate method followed by spectrophotometric assay. Urine OA concentration was determined, using high-performance liquid chromatography. Minimum amount of detectable OA in feline urine was 1 µg/ml. Because of small interfering peaks near the base of the OA peak, the minimum quantifiable concentration of OA was determined to be 5 pg/ml. Urinary OACR was compared in both groups of cats.

Results

Differences in urinary OACR were not detected between clinically normal cats and cats with HL. Peaks were not detected for urinary OA in any of the 20 clinically normal cats. Of the 20 HL cats, 14 did not have detectable peaks for urinary OA. Of the 6 HL cats that had detectable urinary OA peaks, 3 had values of < 5 µg/ml.

Conclusions

Apparently, OACR does not increase significantly in cats with HL.

Clinical Relevance

Urinary OACR is not a useful diagnostic test for HL in cats. (Am J Vet Res 1999; 60:753–754)
Effect of protein intake during training on biochemical and performance variables in sled dogs
Authors: Reynolds Arleigh J. , Reinhart Gregory A. , Carey Daniel P. , Simmerman Dawn A. , Frank David A. , Kallfelz Francis A.
Published: January 2024

Objective

To determine effects of protein intake on blood variables, plasma volume, and maximal oxygen uptake (Vo2max) in sled dogs undergoing rigorous training.

Animals

32 Alaskan sled dogs, between 2 and 6 years old.

Procedure

Dogs were assigned to 1 of 4 groups on the basis of age, sex, and ability. Isocaloric diets containing 18% (diet A), 23% (diet B), 29% (diet C), or 35% (diet D) of energy as protein were assigned randomly to each group and fed 1 month before and during a 12-week training period. Maximal oxygen uptake was measured at 0 (before training) and 12 weeks. Body weight, protein and energy intake, plasma volume, PCV, hemoglobin concentration, and serum biochemical variables were measured at 0, 8, and 12 weeks.

Results

Serum biochemical variables, PCV, and hemoglobin concentration remained within reference ranges for all dogs. Dogs fed diet A had a decrease in Vo2max and a greater rate of soft tissue injury throughout training, compared with dogs fed the other diets. At 12 weeks, dogs fed diets C and D had greater serum sodium concentration and hemoglobin concentration than did dogs fed diet A. Dogs fed diet D also had more plasma volume at 12 weeks than did dogs of any other group.

Conclusions and Clinical Relevance

Consumption of a diet with 18% dietary protein on an energy basis (3.0 g of protein/kg of body weight) is insufficient to meet the metabolic requirements of sled dogs in training. For intense interval work, a diet with 35% dietary protein as energy (6.0 g of protein/kg) may provide a performance advantage by promoting an increase in plasma volume. (Am J Vet Res 1999;60: 789–795)
Pharmacokinetics and pharmacologic effects of the S(-) isomer of bupivacaine after intravenous and epidural administration in dogs
Authors: Franquelo Carme , Toledo Alfonso , Manubens Jordi , Valladares J. Enric , Cristòfol Carles , Arboix Margarita
Published: January 2024

Objective

To determine pharmacokinetic variables and pharmacologic effects of the S(-) isomer of bupivacaine (S[-]-BPV) in dogs.

Animals

6 adult male Beagles.

Procedure

Dogs received S(-)-BPV (1 mg/kg of body weight) IV, and 15 days later, the same dogs received 1.8 mg/kg epidurally. Pharmacokinetic variables and pharmacologic effects were determined for each route of administration.

Results

After IV administration, plasma concentration versus time curves were adjusted, using biexponential equations that indicated a rapid distribution phase followed by a slower elimination phase, with a mean ± SD half-life of 33.5 ± 17.0 minutes. Mean plasma clearance was 21.0 ± 10.7 ml/min/kg, and mean volume of distribution at steady state was 0.8 ± 0.2 L/kg. After IV administration, mean peak plasma concentration was 2.6 ± 0.7 µg/ml; after epidural administration, it was 0.9 ± 0.5 µg/ml at approximately 3 minutes. Half-life after epidural administration was 5 times longer than that observed after IV administration. Motor block began immediately after the end of epidural administration and lasted for 3 to 4 hours. Changes in systolic blood pressure and heart rate after epidural administration were slight but occurred at the same time that plasma concentration peaked. After IV administration, motor block or variations in physiologic variables studied were not observed.

Conclusions and Clinical Relevance

In dogs, the pharmacologic behavior of S(-)-BPV was similar to that of the bupivacaine racemate, but motor block attributable to S(-)-BPV lasted longer than that attributable to the racemate, with lower plasma concentrations observed at equivalent sample collection times. (AJVR 1999;60:832–835)
Techniques for evaluation of right ventricular relaxation rate in horses and effects of inhalant anesthetics with and without intravenous administration of calcium gluconate
Authors: Grubb Tamara L. , Constable Peter D. , Benson Gordon J. , Foreman Jonathan H. , Olson William O. , Thurmon John C. , Tranquilli William J. , Davis Lloyd E.
Published: January 2024

Objectives

To determine the most repeatable method for evaluating right ventricular relaxation rate in horses and to determine and compare effects of isoflurane or halothane with and without the added influence of intravenously administered calcium gluconate on right ventricular relaxation rates in horses.

Animals

6 Thoroughbred horses from 2 to 4 years old.

Procedure

6 models (2 for monoexponential decay with zero asymptote, 3 for monoexponential decay with variable asymptote, and 1 for biexponential decay) for determining right ventricular relaxation rate were assessed in conscious and anesthetized horses. The 2 methods yielding the most repeatable results then were used to determine right ventricular relaxation rates in horses anesthetized with isoflurane or halothane before, during, and after IV administration of calcium gluconate. Right ventricular pressure was measured, using a catheter-tip high-fidelity pressure transducer, and results were digitized at 500 Hz from minimum rate of change in ventricular pressure.

Results

2 models that used monoexponential decay with zero asymptote repeatedly produced an estimate for relaxation rate and were used to analyze effects of anesthesia and calcium gluconate administration on relaxation rate. Isoflurane and halothane each prolonged right ventricular relaxation rate, with greater prolongation evident in halothane-anesthetized horses. Calcium gluconate attenuated the anesthesia-induced prolongation in right ventricular relaxation rate, with greater response obtained in isoflurane-anesthetized horses.

Conclusions and Clinical Relevance

Right ventricular relaxation rate in horses is assessed best by use of a monoexponential decay model with zero asymptote and nonlinear regression. Intravenous administration of calcium gluconate to isoflurane-anesthetized horses best preserves myocardial relaxant function. (Am J Vet Res 1999;60:872–879)
Solubilization of liver alkaline phosphatase isoenzyme during cholestasis in dogs
Authors: Solter Philip F. , Hoffmann Walter E.
Published: January 2024

Objective

To determine the mechanism by which liver alkaline phosphatase (LALP) isoenzyme is converted from a membrane-bound enzyme to the soluble enzyme during cholestasis.

Sample Population

Serum and tissues from 2 dogs.

Procedure

The LALP was purified by use of affinity chromatography in samples of serum from dogs with complete bile duct obstruction. Gas chromatography/mass spectrometry was used to detect myo-inositol residues that would be evident when serum LALP had been membrane-attached and released by phospholipase activity. Exclusion chromatography, gel electrophoresis, and octyl-sepharose phase separation of the serum isolate were used to confirm cleavage of the hydrophobic membrane anchor. Western immunoblot analysis was used to distinguish release by glycosylphosphatidylinositol phospholipase D (GPI-PLD) from that by glycosylphosphatidylinositol phospholipase C (GPI-PLC). Intact hepatocytes were incubated with canine serum GPI-PLD to test sensitivity of LALP to release by GPI-PLD. Hepatocyte membrane fragments were treated with serum GPI-PLD and mixtures of taurocholate and taurodeoxycholate to test effects of bile acids on LALP release.

Results

Amounts of myo-inositol per mole of serum LALP isolate were equal to amounts detected with LALP isolated from hepatic tissue. Evaluation of results of western immunoblot analysis and electrophoretic mobility suggested release by GPI-PLD rather than by GPI-PLC. Membrane-bound LALP was resistant to serum GPI-PLD activity in the absence of bile acids; however, incubation in the presence of bile acids caused release of LALP.

Conclusions

Solubilization of LALP during cholestasis involves cleavage of its membrane anchor by endogenous GPI-PLD activity. Action of GPI-PLD is likely enhanced by increased concentrations of hepatic bile acids during cholestasis. (Am J Vet Res 1999;60:1010-1015)
Comparison of sedative effects of romifidine following intravenous, intramuscular, and sublingual administration to horses
Authors: Freeman Sarah L. , England Gary C. W.
Published: January 2024

Objective

To compare sedative effects of romifidine following IV, IM, or sublingual (SL) administration in horses.

Animals

30 horses that required sedation for routine tooth rasping.

Procedure

Horses (n = 10/group) were given romifidine (120 μg/kg) IV, IM, or SL. Heart rate, respiratory rate, head height, distance between the ear tips, thickness of the upper lip, response to auditory stimulation, response to tactile stimulation, and degree of ataxia were recorded every 15 minutes for 180 minutes. Tooth rasping was performed 60 minutes after administration of romifidine, and overall adequacy of sedation was assessed.

Results

IV and IM administration of romifidine induced significant sedation, but SL administration did not induce significant sedative effects. Scores for overall adequacy of sedation after IV and IM sedation were not significantly different from each other but were significantly different from scores for horses given romifidine SL. Sedative and other effects varied among groups during the first 60 minutes after drug administration; thereafter, effects of IV and IM administration were similar.

Conclusions and Clinical Relevance

Onset of action was fastest and degree of sedation was greater after IV, compared with IM, administration of romifidine, but duration of action was longer after IM administration. Sublingual administration did not result in clinically important sedative effects. (Am J Vet Res 1999;60:954-959)