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Biomedical subjects

N D Cohen

Publications and source records attributed to N D Cohen.

At least 19 recordsLinked to original sources

Antimicrobial activity of gallium against virulent Rhodococcus equiin vitro and in vivo.

Rhodococcus equi, a facultative intracellular bacterium, causes severe pneumonia in foals. Evidence suggests that most foals become infected very early in life, when they have immature or ineffective innate immune responses. This study evaluated the antimicrobial activity of gallium against R. equi, as a potential chemoprophylactic and therapeutic agent. Rhodococcus equi was grown in media with various concentrations of gallium nitrate (GN), with and without excess iron. GN significantly inhibited growth and killed R. equi, and these effects were abolished with excess iron. Antimicrobial effects of Ga appear to be related to its interference with iron metabolism. Mice were treated orally with gallium maltolate (GaM), 10 or 50 mg/kg BW, or distilled H2O prior to and after experimental infection with R. equi. Six days post-infection, organs were harvested and R. equi concentrations assessed, and serum gallium concentrations determined. GaM was absorbed in a dose-dependent manner, and R. equi tissue burdens were greater in control mice than in all GaM-treated mice. GaM may aid in the control of disease by preventing development of overwhelming R. equi tissue burdens prior to the establishment of requisite innate and adaptive immune responses.

Actinomycetales Infections↗

Are feeding practices associated with duodenitis-proximal jejunitis?

REASONS FOR PERFORMING STUDY: Feeding concentrate has been putatively associated with risk of development of duodenitis-proximal jejunitis (DPJ); however, this association has not been evaluated systematically in a controlled study. OBJECTIVES: To determine whether there was evidence that feeding practices were associated with increased odds of developing DPJ employing a case control study. HYPOTHESIS: The amount of concentrate fed daily to horses is significantly greater among horses that develop DPJ than control horses with either lameness or other types of colic. METHODS: Feeding practices of cases of DPJ diagnosed between 1997 and 2003 were compared with those of 2 populations of control horses (colic controls and lameness controls) admitted to the clinic from the same time period. Following multiple imputation of missing data, comparisons were made using polytomous logistic regression. RESULTS: Horses with DPJ were fed significantly more concentrate and were significantly more likely to have grazed pasture than either control populations; DPJ horses were significantly more likely to be female than were lameness horses. Results were unchanged after adjusting for bodyweight of the horse. CONCLUSIONS: Feeding and grazing practices differ among horses with DPJ relative to horses with other forms of colic and lame horses. POTENTIAL RELEVANCE: The observed magnitudes of association were not sufficiently strong to merit diagnostic/predictive application; however, these observations, if substantiated by other studies, might provide important aetiological clues.

Animal Feed↗

Factors influencing pre-race serum concentration of total carbon dioxide in Thoroughbred horses racing in California.

REASONS FOR PERFORMING STUDY: Many racing jurisdictions monitor pre-race serum concentration of total carbon dioxide (TCO2) among racing horses. To our knowledge, factors influencing concentration of TCO2 among horses participating in racing have not been systematically evaluated and reported. OBJECTIVES: To determine if characteristics of horses and racing conditions routinely recorded were significantly associated with pre-race concentration of TCO2, while accounting for and estimating effects of trainer and horse. METHODS: Pre-race serum TCO2 concentrations from 5028 starts made by 2,349 horses trained by 287 trainers at 2 racetracks in California during 2005 were examined. Data regarding characteristics of starters and race conditions obtained from a commercial database were recorded for each start. Data were analysed using mixed-effects, with TCO2 concentration as the dependent variable, and trainer and horse nested within trainer as random effects. RESULTS: Sex, class and distance of race, frusemide administration and cloudy weather conditions were significantly (P<0.001) associated with pre-race TCO2 concentration. Horses that finished in the top 3 positions had values that were slightly (0.2 mmol/) but significantly (P<0.001) greater than horses not finishing in the top 3. There were significant effects of trainer on pre-race TCO2 concentration. CONCLUSIONS: A variety of factors may influence pre-race TCO2 concentration in horses. Horses with better performance tend to have higher pre-race TCO2 concentrations. POTENTIAL RELEVANCE: TCO2 concentration is associated with improved performance although the magnitude of effect was quite small. Regulatory programmes based on monitoring should consider the influence of other factors on TCO2 concentration.

Administration, Oral↗

Study of serum amyloid A concentrations as a means of achieving early diagnosis of Rhodococcus equi pneumonia.

REASONS FOR PERFORMING STUDY: Prognosis of Rhodococcus equi pneumonia can be challenging because the course of the disease is often insidious and overt clinical signs are subtle. Early diagnosis is considered desirable because it may offer the chance of more successful implementation of treatment and, thereby, improved outcome. Serological tests have previously failed to be accurate for early detection or diagnosis. Measurement of serum amyloid A (SAA) prior to and at the time of clinical signs was therefore chosen in order to assess its potential clinical use. OBJECTIVE: To determine whether SAA concentrations differentiate foals affected with R. equi pneumonia from unaffected foals, either prior to the onset of disease or at the time of onset of clinical signs. HYPOTHESIS: SAA concentrations are significantly higher among foals that develop R. equi pneumonia than in foals from the same environment that remain clinically unaffected. METHODS: Serum samples were obtained from 212 foals 7-14 days and 196 foals 21-28 days post partum, and from affected foals and age-matched controls at the time of onset of signs of pneumonia. SAA concentration was determined for each sample. RESULTS: There were no significant differences between SAA concentrations of foals with R. equi and clinically unaffected foals during the 2 periods of examination or at the time of onset of clinical signs of R. equi pneumonia. CONCLUSIONS: Concentrations of SAA are variable among foals with R. equi pneumonia and cannot be used reliably either as an ancillary diagnostic tool or to screen for early detection of disease during the first month post partum. POTENTIAL RELEVANCE: Bimonthly monitoring concentration of SAA is not useful as a screening test for early detection of R. equi pneumonia and does not facilitate diagnosis of this disease when used according to the protocol of this study.

Actinomycetales Infections↗

Meal size and starch content affect gastric emptying in horses.

REASONS FOR PERFORMING STUDY: Feeding practices have been associated with colic in horses. If meal size and composition have an effect on gastric emptying, this could be one of the mechanisms by which feeding practices are related to the occurrence of colic. OBJECTIVES: To evaluate the effect of meal size and starch content on solid phase gastric emptying. METHODS: Solid phase gastric emptying of 3 different radiolabelled meals, small low-starch (SmLS), small high-starch (SmHS) and large high-starch (LgHS) meals, was measured in 5 horses by scintigraphy using 99mTc-disofenin. Data were compared among meals using nonlinear mixed-effects models and paired t tests. RESULTS: On a percentage basis, SmHS emptied significantly faster than LgHS and SmLS emptied significantly faster than SmHS meals. However, when meals of unequal size were compared by emptying rate in g/min and Kcal/min, LgHS emptied significantly faster than SmHS. CONCLUSIONS: Meal size and composition affect gastric emptying. POTENTIAL RELEVANCE: Further work needs to be performed in order to substantiate the possibility of a relationship between digestive functions and occurrence of colic and gastric ulcers.

Animal Feed↗

Temporal changes in cytokine expression of foals during the first month of life.

Foals are uniquely susceptible to a wide variety of opportunistic infections normally associated with immunodeficiencies. Little is understood about the immune system of foals during the neonatal period. An apparent age-related susceptibility predisposes neonatal foals to infectious diseases and hinders therapeutic and preventative interventions for these diseases. Cytokine expression is correlated with the type of immune response as well as the severity of a disease. In this study, we measured foal peripheral blood mononuclear cell (PBMC)-specific mRNA cytokine expression from 72 foals from three different farms during the first 4 weeks of life. Interleukin-1alpha (IL-1alpha), IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p35, IL-12p40, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta1 (TGF-beta1) were cloned and transcribed in vitro to generate antisense probes for ribonuclease protection assays. Using linear mixed-effect models, we determined that IFN-gamma, TGF-beta1, and IL-1alpha increased significantly (P<0.05) with age.

Age Factors↗

The effects of xylazine, detomidine, acepromazine and butorphanol on equine solid phase gastric emptying rate.

The aim of this study was to measure the effects of specific commonly used sedative protocols on equine solid phase gastric emptying rate, using the 13C-octanoic acid breath test (13C-OABT). The gastric emptying of a standard 13C-labelled test meal was measured once weekly in 8 mature horses over two 4 week treatment periods. Each horse acted as its own control. In treatment Period 1, saline (2 ml i.v.), xylazine (0.5 mg/kg i.v.), detomidine (0.01 mg/kg i.v.) or detomidine/butorphanol combination (0.01/0.02 mg/kg i.v.) was administered in randomised order after ingestion of the test meal. During treatment Period 2, test meal consumption was followed by saline, xylazine (1.0 mg/kg i.v.), or detomidine (0.03 mg/kg i.v.) administration, or preceded by acepromazine (0.05 mg/kg i.m.) in randomised order. The 13C:12C ratio of sequential expiratory breath samples was determined by isotope ratio mass spectrometry, and used to measure the gastric half-emptying time, t 1/2, and duration of the lag phase, t lag, for each of the 64 tests. In treatment Period 1, detomidine/butorphanol prolonged both t 1/2 and t lag with respect to xylazine 0.5 mg/kg and the saline control (P < 0.05). In Period 2, detomidine 0.03 mg/kg delayed each parameter with respect to saline, acepromazine and xylazine 1.0 mg/kg (P < 0.001). Xylazine 1.0 mg/kg also lengthened t lag relative to the saline control (P = 0.0004), but did not cause a significant change in t 1/2. Comparison of treatment periods showed that the inhibitory effect of detomidine on gastric emptying rate was dose related (P<0.05). These findings may have clinical significance for case selection when these agents are used for purposes of sedation and/or analgesia.

Acepromazine↗

Quantitative detection of atropine-delayed gastric emptying in the horse by the 13C-octanoic acid breath test.

The 13C-octanoic acid breath test has been correlated significantly to radioscintigraphy for measurement of gastric emptying indices in healthy horses. The objective of this study was to investigate the validity of the test for measurement of equine delayed gastric emptying, prior to its potential clinical application for this purpose. A model of atropine-induced gastroparesis was used. Gastric emptying rate was measured twice in 8 horses using concurrent radioscintigraphy and/or breath test after treatment i.v. with either atropine (0.035 mg/kg bwt) or saline in randomised order. Analysis of both data sets demonstrated that the atropine treatment had caused a significant delay in gastric emptying rate. Paired breath test data showed an atropine-induced delay in gastric half-emptying time (t 1/2), with no overlap in the 99% CI range (P < 0.001). Significant correlations were found between scintigraphy and 13C-octanoic acid breath test for calculation of both t 1/2 (P < 0.01) and lag phase duration (P < 0.05) in the atropine-delayed emptying results. The mean (s.d.) bias in breath test t 1/2 when compared with scintigraphy was 1.78 (0.58) h. The results demonstrated that the 13C-octanoic acid breath test was an effective diagnostic modality for the measurement of equine delayed gastric emptying. The technique offers advantages to existing methods for clinical investigation, as it is noninvasive, not radioactive, quantitative and requires minimal equipment or training to perform.

Animals↗

Feeding practices associated with colic in horses.

OBJECTIVE: To determine whether specific feeding practices were associated with development of colic in horses. DESIGN: Prospective matched case-control study. ANIMALS: 364 horses examined by veterinarians in private practice in Texas because of colic (cases; n = 182) or any other reason (controls; 182). PROCEDURE: Participating veterinarians were sent forms at the beginning of the study to collect information on signalment, feeding management practices, farm management practices, and preventive medical treatments. Case and control horses were compared by use of conditional logistic regression to identify factors associated with colic. RESULTS: Risk factors for colic were a recent change in batch of hay, decreased exposure to pasture, a recent change in type of grain or concentrate fed, feeding > 2.7 kg (6 lb) of oats/d, feeding hay from round bales, and Thoroughbred breed. Recent anthelmintic administration decreased the risk of colic. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that certain changes in diet (eg, change in batch of hay, change in type of grain or concentrate, feeding hay from round bales) and management (eg, decreased availability of pasture) increase the risk of colic in horses.

Animal Feed↗

Quality of tissue specimens obtained endoscopically from the duodenum of dogs and cats.

OBJECTIVE: To evaluate quality of duodenal tissue specimens obtained endoscopically from dogs and cats and submitted to 1 of 2 diagnostic laboratories for evaluation. DESIGN: Case series. SAMPLE POPULATION: Slides from 50 consecutive canine and 50 consecutive feline endoscopically obtained duodenal tissue specimens submitted to laboratory 1 and 49 consecutive canine and 46 consecutive feline specimens submitted to laboratory 2. PROCEDURE: Slides were examined independently by 3 investigators, and each tissue piece on each slide was classified as clearly inadequate, questionable, or clearly adequate on the basis of 4 criteria. An overall score was then assigned to the slide. RESULTS: Slides from laboratory 1 were more likely to be scored as clearly adequate and less likely to be scored as clearly inadequate than slides from laboratory 2. Clearly adequate slides from laboratory 1 had a higher number of clearly adequate pieces of tissue than did clearly adequate slides from laboratory 2. Slides scored as clearly adequate had a higher number of individual tissue pieces than did slides scored as clearly inadequate. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that the quality of endoscopically obtained duodenal tissue specimens submitted to laboratories can vary, possibly because of differences in experience of individuals collecting biopsy specimens. Results suggest that at least 8 individual tissue pieces should be submitted when performing endoscopic biopsy of the duodenum in dogs and cats.

Animals↗

Risk factors associated with development of postoperative ileus in horses.

OBJECTIVE: To determine risk factors associated with development of postoperative ileus in horses undergoing surgery for colic. DESIGN: Case-control study. ANIMALS: 69 horses that developed ileus after surgery for colic and 307 horses that did not develop postoperative ileus. PROCEDURE: Signalment, history, clinicopathologic data, treatment, lesions, and outcome were obtained from medical records. RESULTS: Variables associated with increased risk of postoperative ileus included age > 10 years, Arabian breed, PCV > or = 45%, high serum concentrations of protein and albumin, anesthesia > 2.5 hours' duration, surgery > 2 hours' duration, resection and anastomosis, and lesions in the small intestine. Enterotomy reduced the risk of postoperative ileus. After multivariate logistic regression, the final model included the variables Arabian breed, PCV > or = 45%, lesion type, duration of surgery (> 2 hours vs < or = 2 hours), and pelvic flexure enterotomy. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that by evaluating certain factors, horses at increased risk of postoperative ileus may be recognized before the condition develops. Preventative treatment and early intervention may be instituted in these horses. Shortening surgery time and performing an enterotomy may decrease the probability of horses developing postoperative ileus.

Age Factors↗

Statistical evaluation of the regulatory guidelines for use of furosemide in race horses.

The pharmacokinetic behavior of furosemide concentrations in performance horses is of great interest to the equine industry and equine researchers. Specifically, such information is useful for the evaluation of the existing guidelines in several racing jurisdictions and for the possible development of new guidelines for varying time periods after administration. We studied several approaches within the framework of nonlinear mixed effects models to increase the accuracy of evaluating these guidelines. Theoretical properties of the proposed methods were examined and the variances of the resulting estimators compared. Their numerical performances were further evaluated through simulations. Finally, we applied these methods to a furosemide concentration profile data set and used our findings to address certain important practical issues.

Animals↗

Prevalence of virulent Rhodococcus equi in soil from five R. equi-endemic horse-breeding farms and restriction fragment length polymorphisms of virulence plasmids in isolates from soil and infected foals in Texas.

Rhodococcus equi isolates (462) obtained from 64 soil samples collected on 5 R. equi-endemic horse-breeding farms and isolates from 100 infected foals in Texas were examined to determine the prevalence and genotypic diversity of virulence-associated plasmids. Isolates were tested for the presence of 15-17-kDa virulence-associated protein antigens (VapA) by immunoblotting and virulence-associated plasmids by PCR. Plasmid DNAs were isolated and analyzed by digestion with restriction endonucleases for estimation of size and comparison of polymorphisims. Rhodococcus equi were isolated from soil of all 5 farms; however, virulent R. equi were only isolated from 3 of the 5 farms and represented 18.8% (87 of 462) of total isolates. Of the 87 virulent soil isolates, 56 (64.5%) contained an 85-kb type I plasmid, 23 (26.4%) an 87-kb type I plasmid, 7 (8%) a newly defined 85-kb type III plasmid (Tx 43), and 1 (1.1%) a newly defined 85-kb type IV plasmid (Tx 47). Of the 100 isolates from infected foals, 96 were virulent. Of the 96 virulent isolates, 51 (53.1%) contained an 85-kb type I plasmid, 39 (40.6%) an 87-kb type I plasmid, 4 (4.2%) an 85-kb type III plasmid (Tx 43), and 2 (2.1%) an 85-kb type IV plasmid (Tx 47). There are at least 4 different R. equi virulence-associated plasmids in Texas, 2 of which have not previously been described. Based upon virulence plasmid typing, there is geographic diversity among isolates of R. equi from clinical and environmental samples on horse-breeding farms in Texas. There is not a strong correlation between the presence of virulent R. equi in farm soils and the R. equi disease status of those farms.

Actinomycetales Infections↗

Estimation of the probability for exceeding thresholds of urine specific gravity and plasma concentration of furosemide at various intervals after intravenous administration of furosemide in horses.

OBJECTIVE: To estimate the probability of concurrently exceeding thresholds for plasma concentration of furosemide and urine specific gravity after IV administration of furosemide in horses. ANIMALS: 12 mature healthy Thoroughbred (n = 6) or Quarter Horse (6) mares. PROCEDURE: Venous blood was collected from each horse prior to and 0.25, 0.5, 0.75, 1, 2, 3, 4, 4.5, 5, and 6 hours after IV administration of 250 mg (first experiment) or 500 mg (second experiment) of furosemide. Urine was collected hourly between 1 and 6 hours after administration of furosemide at both doses. Concentrations of furosemide were determined by use of an ELISA. Concentration of furosemide and urine specific gravity was modeled as a function of time, accounting for inter- and intrahorse variabilities. On the basis of pharmacokinetic and specific gravity data, the probability of exceeding a concentration of 100 ng of furosemide/ml as a function of time was determined, using a semiparametric smooth functional averaging method. A bootstrap approach was used to assess the inherent variation in this estimated probability. RESULTS: The estimated probability of exceeding the threshold of 100 ng of furosemide/ml and urine specific gravity < 1.012 was approximately 0% between 4.0 and 5.5 hours after IV administration of 250 mg of furosemide/horse, and ranged from 0 to 1% between 4 and 5.5 hours after IV administration of 500 mg of furosemide/horse. The probability of a horse being falsely identified as in violation of regulatory concentrations was inversely associated with time. CONCLUSIONS AND CLINICAL RELEVANCE: Coupling plasma furosemide concentration with urine specific gravity testing will greatly reduce the chance that some horses are misclassified as being in violation of regulatory concentrations.

Animals↗

Estimation of the probability for exceeding a threshold concentration of furosemide at various intervals after intravenous administration in horses.

OBJECTIVE: To estimate the probability for exceeding a threshold concentration of furosemide commonly used for regulatory purposes after IV administration of furosemide in horses. ANIMALS: 12 mature healthy horses (6 Thoroughbreds and 6 Quarter Horses). PROCEDURE: Venous blood was collected from each horse prior to and 0.25, 0.5, 0.75, 1, 2, 3, 4, 4.5, 5, and 6 hours after administration of 250 or 500 mg of furosemide. Concentrations of furosemide were determined, using an ELISA. Concentration of furosemide was modeled as a function of time, accounting for inter- and intrahorse variabilities. On the basis of pharmacokinetic data, the probability for exceeding a concentration of 100 ng/ml as a function of time was determined, using a semiparametric smooth functional averaging method. A bootstrap approach was used to assess inherent variation in this estimated probability. RESULTS: The estimated probability of exceeding the threshold of 100 ng of furosemide/ml ranged from 11.6% at 4 hours to 2.2% at 5.5 hours after IV administration of 250 mg of furosemide/horse and 34.2% at 4 hours to 12.3% at 5.5 hours after IV administration of 500 mg of furosemide/horse. The probability of a horse being falsely identified in violation of regulatory concentrations was inversely associated with time and positively associated with dose. CONCLUSIONS AND CLINICAL RELEVANCE: Interhorse variability with respect to pharmacokinetics of furosemide will result in misclassification of some horses as being in violation of regulatory concentrations.

Animals↗

Osseous sequestration in cattle: 110 cases (1987-1997).

OBJECTIVE: To determine risk factors for development of sequestra in cattle and identify factors associated with a successful outcome. DESIGN: Retrospective study. ANIMALS: 110 cattle. PROCEDURE: Medical records of cattle treated at veterinary teaching hospitals in North America were reviewed. To determine risk factors for osseous sequestration, breed, age, and sex of cattle with osseous sequestration were compared with breed, age, and sex of all other cattle admitted during the study period. RESULTS: 110 cattle were included in the study. Three had 2 sequestra; thus, 113 lesions were identified. Most sequestra were associated with the bones of the extremities, most commonly the third metacarpal or third metatarsal bone. Ninety-two animals were treated surgically (i.e., sequestrectomy), 7 were treated medically, 3 were initially treated medically and were then treated surgically, and 8 were not treated. Follow-up information was available for 65 animals treated surgically and 6 animals treated medically. Fifty-one (78%) animals treated surgically and 5 animals treated medically had a successful outcome. Cattle that were 6 months to 2 years old had a significantly increased risk of developing a sequestrum, compared with cattle < 6 months old. Cattle in which sequestrectomy was performed with the aid of local anesthesia were significantly more likely to undergo 2 or more surgical procedures than were cattle in which sequestrectomy was performed with the aid of general anesthesia. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that sequestrectomy will result in a successful outcome for most cattle with osseous sequestration.

Age Factors↗