Search Results

You are looking at 1 - 9 of 9 items for

  • Author or Editor: R. J. MacKay x
  • Refine by Access: All Content x
Clear All Modify Search

Abstract

Objectives—To measure serum polymyxin B concentration after single and repeated IV infusions in horses.

Animals—5 healthy horses.

Procedures—In study 1, 1 mg (6,000 U) of polymyxin B/kg was given IV and blood samples were collected for 24 hours. In study 2, 1 mg of polymyxin B/kg was given IV every 8 hours for 5 treatments and blood samples were collected until 24 hours after the last dose. Polymyxin B concentration was measured as the ability to suppress nitrite production by murine macrophages stimulated with lipopolysaccharide and interferon-α. Urine was collected prior to the first drug infusion and 24 hours after the fifth drug infusion for determination of urinary γ-glutamyl transferase (GGT)to-creatinine ratios.

Results—In study 1, mean ± SEM maximal serum polymyxin B concentration was 2.93 ± 0.38 μg/mL. Polymyxin B was undetectable 18 hours after infusion. In study 2, maximal polymyxin B concentrations after the first and fifth doses were 2.98 ± 0.81 μg/mL and 1.91 ± 0.50 μg/mL, respectively. Mean trough concentration for all doses was 0.22 ± 0.01 μg/mL. A significant effect of repeated administration on peak and trough serum concentration was not detected. Urine GGT-to-creatinine ratios were not affected by polymyxin B administration.

Conclusions and Clinical Relevance—Polymyxin B given as multiple infusions to healthy horses by use of this protocol did not accumulate in the vascular compartment and appeared safe. Results support repeated IV use of 1 mg of polymyxin B/kg at 8-hour intervals as treatment for endotoxemia.

Full access
in American Journal of Veterinary Research
in Journal of the American Veterinary Medical Association

SUMMARY

A monoclonal antibody (mab) against equine tumor necrosis factor-α (Eq tnf) was used to investigate the role of tnf in cytokine, eicosanoid, and metabolic responses of Miniature Horses given endotoxin. Plasma concentrations of interleukin 6 (il-6), lactate, thromboxane A2 metabolite, and prostacyclin metabolite (6-keto-pgf ) were measured in 10 Miniature Horses given 0.25 µg of lipopolysaccharide (lps; Escherichia coli O55:B5)/kg of body weight. Five horses were given Eq tnf mab and 5 were given isotype-matched mab as control. All horses were given 1.86 mg of antibody/kg by iv infusion, 5 minutes before lps was given iv. Blood samples were taken 20 minutes before and at multiple intervals for 24 hours after lps was given. Interleukin 6 bioactivity in plasma was measured, using il-6-dependent cell line (B9). Eicosanoid activities were assessed by enzyme immunoassay, and plasma lactate concentration was determined enzymatically. Data were analyzed by anova and Tuke's honest significant difference test for significant (P < 0.05) effect of treatment. Horses given Eq tn mab had significantly (P < 0.050) lower peak mean ± sem il-6 (59 ± 29 U/ml), lactate (16 ± 2.00 mg/dl), and 6-keto-pgf (254 ± 79 pg/ml) values then did horses given control mab (880 ± 375 U/ml for il-6; 26 ± 0.04 mg/dl for lactate; and 985 ± 290 pg/ml for 6-keto-pgf ). There was no effect of anti-tnf treatment on lps-induced thromboxane A2 metabolite production. Tumor necrosis factor mediated il-6, lactate, and prostacyclin responses, without affecting thromboxane production in horses given lps.

Free access
in American Journal of Veterinary Research

SUMMARY

Tumor necrosis factor-α (tnf) is an important mediator of endotoxin-induced pathologic changes. To help define the role of tnf in equids with endotoxemia, the effects of pretreatment with a murine monoclonal antibody (mab) against equine tnf were evaluated in Miniature Horses given endotoxin. Five horses were given tnf mab at a dosage of 1.86 mg/kg of body weight, iv, and 5 were given control mab. Five minutes later, lipopolysaccharide (lps; Escherichia coli O55:B5), 0.25 µg/kg, was given to all horses by bolus iv infusion. Clinical signs of disease were monitored at intervals up to 24 hours after lps infusion, and blood was taken for determination of hematologic and clinical responses of horses given wbc count, pcv, plasma total protein concentration, plasma tnf activity, and serum mab concentration. Reduction of plasma tnf activity in anti-tnf-treated horses was highly significant (P < 0.001), compared with that in control horses. Horses given tnf mab had significantly improved clinical abnormality score (P < 0.010), lower heart rate (P < 0.001), and higher wbc count (P < 0.001), compared with horses given control mab. Rectal temperature, respiratory rate, pcv, and plasma total protein concentration were not significantly different between groups. Serum mab concentration peaked at 68 µg/ml 30 minutes after the end of antibody infusion in both groups. Neutralization of lps-induced tnf activity reduced the hematologic and clinical responses of horses given lps iv.

Free access
in American Journal of Veterinary Research

SUMMARY

Serum and plasma from horses injected with endotoxin was examined for cytotoxic activity. Each of the cell lines, L929 and WEHI 164 clone 13, was sensitive to the cytotoxic effects of equine serum; however, a precipitation artifact caused by the use of isopropanol in the WEHI assay limited the use of this assay to samples containing <2 mg of protein/ml. In foals treated with a sublethal iv bolus of 5 μg of lipopolysaccharide (LPS)/kg and in adult horses given a low-dose continuous infusion of LPS (30 ng/ kg/h for 4 hours), cytotoxic activity was detected in all serum or plasma samples taken between 30 minutes and 4 hours after LPS infusion began. In horses given either continuous or bolus lps infusions, circulating cytotoxic activity peaked at 1 to 2 hours before decreasing sharply. The onset of pyrexia after lps infusion coincided with the appearance of circulating cytotoxic activity, but the temperature remained high, even after cytotoxic activity disappeared. Treatment of horses with flunixin meglumine (1 mg/kg) appeared to blunt the pyrexic effect of low-dose continuous LPS infusion, but had no significant effect on circulating cytotoxic activity. Incubation of serum samples with an antibody raised against a portion of human tumor necrosis factor (tnf) resulted in the removal of >90% of serum cytotoxicity, suggesting strongly that the cytotoxic activity was attributable to tnf. These findings are consistent with the hypothesis that tnf is an early acting mediator of the effects of endotoxin in the horse.

Free access
in American Journal of Veterinary Research

Abstract

Objective—To estimate prevalence of and identify risk factors for fecal Salmonella shedding among hospitalized horses with signs of gastrointestinal tract disease.

Design—Cross-sectional study.

Animals—465 hospitalized horses with gastrointestinal tract disease.

Procedure—Horses were classified as positive or negative for fecal Salmonella shedding during hospitalization by means of standard aerobic bacteriologic methods. The relationship between investigated exposure factors and fecal Salmonella shedding was examined by means of logistic regression.

Results—The overall prevalence of fecal Salmonella shedding was 13%. Salmonella serotype Newport was the most commonly isolated serotype (12/60 [20%]), followed by Anatum (8/60 [13%]), Java (13%), and Saint-paul (13%). Foals with gastrointestinal tract disease were 3.27 times as likely to be shedding Salmonella organisms as were adult horses with gastrointestinal tract disease. Adult horses that had been treated with antimicrobial drugs prior to hospitalization were 3.09 times as likely to be shedding Salmonella organisms as were adult horses that had not been treated with antimicrobial drugs prior to hospitalization. Adult horses that underwent abdominal surgery were 2.09 times as likely to be shedding Salmonella organisms as were adult horses that did not undergo abdominal surgery.

Conclusions and Clinical Relevance—Results suggest that a history of exposure to antimicrobial drugs prior to hospitalization and abdominal surgery during hospitalization were associated with Salmonella shedding in adult horses with gastrointestinal tract disease. Foals with gastrointestinal tract disease were more likely to shed Salmonella organisms than were adult horses with gastrointestinal tract disease. (J Am Vet Med Assoc 2004;225:275–281)

Full access
in Journal of the American Veterinary Medical Association

Abstract

OBJECTIVE

To compare analgesic efficacy and fetal effects between transdermal administration of fentanyl and IM administration of buprenorphine in pregnant sheep.

ANIMALS

12 healthy pregnant ewes.

PROCEDURES

Before study initiation, each ewe was confirmed pregnant with a single fetus between 113 and 117 days of gestation. Ewes were randomly assigned to receive buprenorphine (0.01 mg/kg, IM, q 8 h for 48 hours beginning 1 hour before anesthesia induction; n = 6) or fentanyl (a combination of transdermal fentanyl patches sufficient to deliver a dose of 2 μg of fentanyl/kg/h applied between the dorsal borders of the scapulae 24 hours before anesthesia induction; 6). Ewes were anesthetized and underwent a surgical procedure to instrument the fetus with an arterial catheter and place a catheter in utero for collection of amniotic fluid samples. Physiologic variables and behavioral changes indicative of pain were assessed, and amniotic fluid and blood samples from ewes and fetuses were collected for determination of drug concentrations at predetermined times.

RESULTS

Both protocols provided acceptable postoperative analgesia with no adverse effects observed in the ewes or fetuses. Compared with the buprenorphine protocol, the fentanyl protocol induced more profound analgesia, decreased the requirement for isoflurane during surgery, and was associated with a shorter anesthesia recovery time. Fetal indices did not differ significantly between the 2 analgesic protocols.

CONCLUSIONS AND CLINICAL RELEVANCE

Results indicated that both protocols provided acceptable analgesia. However, the fentanyl protocol was superior in regard to the extent of analgesia induced, inhalant-sparing effects, and anesthesia recovery time.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To examine the relationship between abdominal surgery and nosocomial Salmonella infections and the relationship between high caseload in combination with abdominal surgery and nosocomial Salmonella infections in hospitalized horses with signs of gastrointestinal tract disease.

Animals—140 horses.

Design—Case-control study.

Procedures—To accomplish the first objective, 1 to 4 control horses were matched with each nosocomial case horse on the basis of admission date of a primary case horse. The frequency of abdominal surgery and other investigated exposure factors were compared between nosocomial case horses and control horses. For the second objective, 4 control horses were matched with each nosocomial case horse on the basis of year of admission. The frequency of high caseload (≥ 26 inpatients), abdominal surgery, and other factors was compared between nosocomial case horses and control horses.

Results—The odds of nosocomial Salmonella infection were 8 times as high (odds ratio = 8.2; 95% confidence interval = 1.11, 60.24) in horses that underwent abdominal surgery, compared with the odds for horses that did not undergo surgery. High caseload alone or in combination with abdominal surgery was not associated with increased risk of nosocomial Salmonella infection.

Conclusions and Clinical Relevance—Abdominal surgery was identified as a risk factor for nosocomial Salmonella infections in horses. Horses that undergo abdominal surgery require enhanced infection control and preventative care. Risk of nosocomial Salmonella infections may be reduced by implementation of biosecurity measures (such as the use of plastic boots, gloves, and footbaths) immediately after surgery.

Full access
in Journal of the American Veterinary Medical Association