Biomedical subjects

Noah D Cohen

Publications and source records attributed to Noah D Cohen.

At least 19 recordsLinked to original sources

PubMed2025

Nebulization of an mRNA-encoded monoclonal antibody for passive immunization of foals against Rhodococcus equi.

Inhalation of Rhodococcus equi causes severe pneumonia in humans and animals worldwide, most commonly affecting horse foals. The standard for preventing R. equi pneumonia in foals is transfusion of hyperimmune plasma, which is expensive and carries the risk of adverse effects. Our goal was to passively immunize foals against R. equi by nebulizing mRNA encoding an equine monoclonal antibody (mAb) against the virulence-associated protein A (VapA) directly into the lungs. VapA-specific memory B cells from an immunized horse were used to identify and select the sequence for an equine immunoglobulin (Ig)G1 mAb. In vitro-transcribed mRNA encoding this sequence expressed full-length, VapA-specific mAbs in vitro and safely and effectively produced intrapulmonary mAb in foals for at least 5 days following nebulization. These findings establish a platform to generate mRNA-encoded mAbs for immunotherapeutic and immunoprophylactic applications in horses and demonstrate the feasibility of delivering nebulized mRNA-mAb for intrapulmonary mAb expression in neonates.

Animals↗

PubMed2007

Evaluation of fecal samples from mares as a source of Rhodococcus equi for their foals by use of quantitative bacteriologic culture and colony immunoblot analyses.

OBJECTIVE: To determine whether mares are a clinically important source of Rhodococcus equi for their foals. SAMPLE POPULATION: 171 mares and 171 foals from a farm in Kentucky (evaluated during 2004 and 2005). PROCEDURES: At 4 time points (2 before and 2 after parturition), the total concentration of R equi and concentration of virulent R equi were determined in fecal specimens from mares by use of quantitative bacteriologic culture and a colony immunoblot technique, respectively. These concentrations for mares of foals that developed R equi-associated pneumonia and for mares with unaffected foals were compared. Data for each year were analyzed separately. RESULTS: R equi-associated pneumonia developed in 53 of 171 (31%) foals. Fecal shedding of virulent R equi was detected in at least 1 time point for every mare; bacteriologic culture results were positive for 62 of 171 (36%) mares at all time points. However, compared with dams of unaffected foals, fecal concentrations of total or virulent R equi in dams of foals with R equi-associated pneumonia were not significantly different. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that dams of foals with R equi-associated pneumonia did not shed more R equi in feces than dams of unaffected foals; therefore, R equi infection in foals was not associated with comparatively greater fecal shedding by their dams. However, detection of virulent R equi in the feces of all mares during at least 1 time point suggests that mares can be an important source of R equi for the surrounding environment.

Actinomycetales Infections↗

PubMed2006

Effect of hyperimmune plasma on the severity of pneumonia caused by Rhodococcus equi in experimentally infected foals.

This study evaluated the prophylactic effectiveness of hyperimmune plasma (HIP) as an aid in the prevention of pneumonia caused by experimental infection with Rhodococcus equi. Thirty neonatal foals were administered R. equi HIP or saline at 2 days of age and were infected with virulent R. equi at 7 days. All foals developed signs or symptoms of respiratory disease. Radiographic scores on day 28 and neutrophil concentrations on day 49 were significantly greater in control foals, and time to respiratory effort score of 2 or higher was significantly shorter for control foals. Three foals, all in the principal group, died or were euthanized before the end of the study, but there was no significant difference in mortality between groups. VapA titers were significantly greater in principal foals. Administration of R. equi HIP decreased the severity of radiographic lesions and prolonged time to increased respiratory effort due to R. equi-induced pneumonia.

Actinomycetales Infections↗

PubMed2005

Musculoskeletal problems associated with lameness and poor performance among horses used for barrel racing: 118 cases (2000-2003).

OBJECTIVE: To identify types of musculoskeletal problems associated with lameness or poor performance in horses used for barrel racing. DESIGN: Retrospective case series. ANIMALS: 118 horses. PROCEDURE: Medical records were reviewed for information on signalment, history, physical and lameness examination findings, diagnostic tests performed, diagnosis, and treatment. RESULTS: Most horses were examined because of lameness (n = 72 [61%]) rather than poor performance (46 [39%]), but owner complaint was not significantly associated with age or body weight of the horse. The most common performance change was refusal or failure to turn properly around the first barrel (19/46 [41%]). The right forelimb (n = 57 [48%]) was most commonly affected, followed by the left forelimb (51 [43%]), the left hind limb (31 [26%]), and the right hind limb (25 [21%]). In 31 horses (26%), both forelimbs were affected, and in 6 (5%), both hind limbs were affected. The most common musculoskeletal problems were forelimb foot pain only (n = 39 [33%]), osteoarthritis of the distal tarsal joints (17 [14%]), suspensory ligament desmitis (15 [13%]), forelimb foot pain with distal tarsal joint osteoarthritis (11 [9%]), and bruised feet (10 [8.5%]). In 81 (69%) horses, the affected joint was treated with intra-articular medications. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that in horses used for barrel racing that are examined because of lameness or poor performance, the forelimbs are more likely to be affected than the hind limbs, with forelimb foot pain and osteoarthritis of the distal tarsal joints being the most common underlying abnormalities.

Animals↗

PubMed2005

Lameness and poor performance in horses used for team roping: 118 cases (2000-2003).

OBJECTIVE: To determine the types of musculoskeletal problems that result in lameness or poor performance in horses used for team roping and determine whether these problems are different in horses used for heading versus heeling. DESIGN: Retrospective study. ANIMALS: 118 horses. PROCEDURE: Medical records of team roping horses that were evaluated because of lameness or poor performance were reviewed to obtain information regarding signalment, primary use (ie, head horse or heel horse), history, results of physical and lameness examinations, diagnostic tests performed, final diagnosis, and treatment. RESULTS: Among horses evaluated by lameness clinicians, the proportion with lameness or poor performance was significantly greater in horses used for heading (74/118) and lower in horses used for heeling (44/118) than would be expected under the null hypothesis. Most horses examined for poor performance were lame. A significantly greater proportion of horses used for heading had right forelimb lameness (26/74 [35%]), compared with horses used for heeling (7/44 [16%]). Horses used for heading had more bilateral forelimb lameness (18/74 [24%]), compared with horses used for heeling (4/44 [9%]). Horses used for heeling had more bilateral hind limb lameness (3/44 [7%]), compared with horses used for heading (0%). The most common musculoskeletal problems in horses used for heading were signs of pain limited to the distal sesamoid (navicular) area, signs of pain in the navicular area plus osteoarthritis of the distal tarsal joints, and soft tissue injury in the forelimb proximal phalangeal (pastern) region. Heeling horses most commonly had signs of pain in the navicular area, osteoarthritis of the metatarsophalangeal joints, and osteoarthritis of the distal tarsal joints. CONCLUSIONS AND CLINICAL RELEVANCE: Horses used for heading were most commonly affected by lameness in the right forelimb. Horses used for heeling had more bilateral hind limb lameness than horses used for heading.

Animals↗

PubMed2005

Farm characteristics and management practices associated with development of Rhodococcus equi pneumonia in foals.

OBJECTIVE: To identify farm characteristics and management practices associated with development of Rhodococcus equi pneumonia in foals. DESIGN: Prospective case-control study. ANIMALS: 5230 foals on 138 breeding farms with 9136 horses. PROCEDURE: During 2003, participating veterinarians provided data from 1 or 2 farms with > or =1 foal with R equi pneumonia and unaffected farms. Data from affected and unaffected farms were compared by use of logistic regression analysis. RESULTS: A number of variables relating to farm size and desirable management practices were significantly associated with increased odds of farms being affected with R equi pneumonia. By use of multivariate logistic regression, affected farms were determined significantly more likely to have raised Thoroughbreds, housed > or =15 foals, used concrete floors in foaling stalls, and tested foals for passive transfer of immunity than unaffected farms. These results remained significant even after accounting for exposure of foals to other breeding farms during the first month of life. Conclusions and Clinical Relevance-Breeding farms with large acreage and a large number of mares and foals have greater odds of being affected by R equi pneumonia. Clinical relevance of associations with Thoroughbred breed and concrete flooring in foaling stalls remains uncertain. Desirable management factors commonly used on farms were not effective for controlling or preventing development of R equi pneumonia. This finding indicates a need to focus on host factors that influence disease development.

Actinomycetales Infections↗

PubMed2005

Protective role of neutrophils in mice experimentally infected with Rhodococcus equi.

Neutrophils are important in controlling early infections with the intracellular bacterium Rhodococcus equi. Antineutrophil monoclonal antibody (RB6-8C5)-induced neutrophil deficiency during the first week after experimental infection of mice with R. equi resulted in more severe disease and significantly increased tissue concentrations of R. equi.

Actinomycetales Infections↗

PubMed2005

Evaluation of a multiplex polymerase chain reaction assay for simultaneous detection of Rhodococcus equi and the vapA gene.

OBJECTIVE: To evaluate sensitivity and specificity of a multiplex polymerase chain reaction (PCR) assay for simultaneous detection of Rhodococcus equi and differentiation of strains that contain the virulence-associated gene (vapA) from strains that do not. SAMPLE POPULATION: 187 isolates of R equi from equine and nonequine tissue and environmental specimens and 27 isolates of bacterial species genetically or morphologically similar to R equi. PROCEDURE: The multiplex PCR assay included 3 gene targets: a universal 311-bp bacterial 16S ribosomal RNA amplicon (positive internal control), a 959-bp R equi-specific target in the cholesterol oxidase gene (choE), and a 564-bp amplicon of the vapA gene. Duplicate multiplex PCR assays for these targets and confirmatory singleplex PCR assays for vapA and choE were performed for each R equi isolate. An additional PCR assay was used to examine isolates for the vapB gene. RESULTS: Results of duplicate multiplex and singleplex PCR assays were correlated in all instances, revealing high specificity and reliability (reproducibility) of the vapA multiplex assay. Of the pulmonary isolates from horses with suspected R equi pneumonia, 97.4% (76/78) yielded positive results for vapA. Seven of 50 (14%) human isolates of R equi yielded positive results for vapA. Six human R equi isolates and 1 porcine isolate yielded positive results for vapB. No isolates with vapA and vapB genes were detected. CONCLUSIONS AND CLINICAL RELEVANCE: The multiplex PCR assay is a sensitive and specific method for simultaneous confirmation of species identity and detection of the vapA gene. The assay appeared to be a useful tool for microbiologic and epidemiologic diagnosis and research.

Actinomycetales Infections↗

PubMed2005

Concentrations of serum amyloid A and lipopolysaccharide-binding protein in horses with colic.

OBJECTIVE: To determine concentrations of 2 acute-phase proteins (serum amyloid A [SAA] and lipopolysaccharide-binding protein [LBP]) in serum samples obtained from horses with colic and identify relationships among these acute-phase proteins and clinical data. ANIMALS: 765 horses with naturally developing gastrointestinal tract diseases characterized by colic (ie, clinical signs indicative of abdominal pain) and 79 healthy control horses; all horses were examined at 2 university teaching hospitals. PROCEDURE: Serum concentrations of SAA and LBP were determined by immunoturbidometric and dot-blot assays, respectively. RESULTS: SAA and LBP concentrations were determined for 718 and 765 horses with colic, respectively. Concentrations of SAA were significantly higher in nonsurvivors than in survivors, and horses with enteritis or colitis and conditions characterized by chronic inflammation (eg, abdominal abscesses, peritonitis, or rectal tears) had SAA concentrations significantly greater than those for horses with other conditions. Serum concentrations of LBP did not correlate with outcome, disease process, or portion of the gastrointestinal tract affected. CONCLUSIONS AND CLINICAL RELEVANCE: Circulating concentrations of SAA were significantly higher at admission in horses with colic attributable to conditions having a primary inflammatory cause (eg, enteritis, colitis, peritonitis, or abdominal abscesses) and were higher in horses that failed to survive the episode of colic, compared with concentrations in horses that survived. Serum concentrations of LBP did not correlate with survival. Analysis of these findings suggests that evaluation of SAA concentrations may be of use in identifying horses with colic attributable to diseases that have inflammation as a primary component of pathogenesis.

Acute-Phase Proteins↗

PubMed2005

Use of a Bayesian risk-mapping technique to estimate spatial risks for mare reproductive loss syndrome in Kentucky.

OBJECTIVE: To estimate spatial risks associated with mare reproductive loss syndrome (MRLS) during 2001 among horses in a specific study population and partition the herd effects into those attributable to herd location and those that were spatially random and likely attributable to herd management. Animals-Pregnant broodmares from 62 farms in 7 counties in central Kentucky. PROCEDURE: Veterinarians provided the 2001 abortion incidence proportions for each farm included in the study. Farms were georeferenced and data were analyzed by use of a fully Bayesian risk-mapping technique. RESULTS: Large farm-to-farm variation in MRLS incidence proportions was identified. The farm-to-farm variation was largely attributed to spatial location rather than to spatially random herd effects. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that there are considerable data to support an ecologic cause and potential ecologic risk factors for MRLS. Veterinary practitioners with more detailed knowledge of the ecology in the 7 counties in Kentucky that were investigated may provide additional data that would assist in the deduction of the causal factor of MRLS via informal geographic information systems analyses and suggest factors for inclusion in further investigations.

Abortion, Veterinary↗

PubMed2005

Temporality of early-term abortions associated with mare reproductive loss syndrome in horses.

OBJECTIVE: To characterize the temporality of dates of breeding and abortion classified as mare reproductive loss syndrome (MRLS) among mares with abortions during early gestation. ANIMALS: 2,314 mares confirmed pregnant at approximately 28 days after breeding from 36 farms in central Kentucky, including 515 mares that had early-term abortions. PROCEDURE: Farm veterinarians and managers were interviewed to obtain data for each mare that was known to be pregnant to determine pregnancy status, breeding date, last date known to be pregnant, and date of abortion. RESULTS: Mares bred prior to April 1, 2001, appeared to be at greatest risk of early-term abortion, both among and within individual farms. Mares bred in mid-February appeared to be at greatest risk of abortion, with an estimated weekly incidence rate of abortion of 66% (95% CI, 52% to 80%). CONCLUSIONS AND CLINICAL RELEVANCE: Mares in central Kentucky bred between mid-February and early March were observed to be at greatest risk of early-term abortion, and risk gradually decreased to a background incidence of abortion of approximately 11%. Mares bred after April 1, 2001, appeared to be at markedly less risk, indicating that exposure to the cause of MRLS likely occurred prior to this date.

Abortion, Veterinary↗

PubMed2005

Effect of an indwelling nasogastric tube on gastric emptying rates of liquids in horses.

OBJECTIVE: To evaluate the effect of an indwelling nasogastric tube on gastric emptying of liquids in horses. ANIMALS: 9 healthy adult horses. PROCEDURE: A randomized block crossover design was used. For treatment group horses, a nasogastric tube was placed and 18 hours later, acetaminophen was administered; the nasogastric tube remained in place until the experiment was complete. For control group horses, a nasogastric tube was passed into t stomach, acetaminophen was administered, and the nasogastric tube was removed immediately. Serial blood samples were collected 15 minutes before and after administration of acetaminophen. Serum concentration of acetaminophen was determined by use of fluorescence polarization immunoassay. The variables, time to maximum acetaminophen concentration (Tmax) and the appearance constant for acetaminophen (Kapp), were determined. The values for Kapp and Tmax in horses with and without prolonged nasogastric tube placement were compared. RESULTS: No significant difference was found in Kapp between horses with and without prolonged nasogastric tube placement; the median difference in Kapp was 0.01 min(-1) (range, -0.48 to 0.80 min(-1). No significant difference was found in Tmax between horses with and without prolonged nasogastric tube placement; the median difference in Tmax was 5 minutes (range, -30 to 50 minutes). Reanalysis of data following the removal of possible outlier values from 1 horse resulted in a significant difference in Tmax between horses with and without prolonged nasogastric tube placement. CONCLUSIONS AND CLINICAL RELEVANCE: Although no clinically important impact of 18 hours of nasogastric intubation was found on gastric emptying in healthy was found among horses.

Acetaminophen↗

PubMed2005

Evaluation of a real-time quantitative polymerase chain reaction assay for detection and quantitation of virulent Rhodococcus equi.

OBJECTIVE: To evaluate a real-time quantitative polymerase chain reaction (QPCR) assay in the detection and quantitation of virulent Rhodococcus equi. SAMPLE POPULATION: 1 virulent, 2 intermediately virulent, and 2 avirulent strains of R. equi and 16 isolates of bacteria genetically related to R. equi. PROCEDURE: The QPCR assay was evaluated for detection and quantitation of the virulence-associated gene (vapA) of R. equi in pure culture and in samples of tracheobronchial fluid, which were inoculated with known numbers of virulent R. equi. Results were compared with those derived via quantitative microbial culture and standard polymerase chain reaction methods. RESULTS: The QPCR assay detected the vapA gene in pure culture of R. equi and in tracheobronchial fluid samples that contained as few as 20 CFUs of virulent R. equi/mL and accurately quantitated virulent R. equi to 10(3) CFUs/mL of fluid. The assay was highly specific for detection of the vapA gene of virulent R. equi and was more sensitive than standard polymerase chain reaction for detection of R. equi in tracheobronchial fluid. CONCLUSIONS AND CLINICAL RELEVANCE: The QPCR assay appears to be a rapid and reliable method for detecting and quantitating virulent R. equi. The accuracy of the QPCR assay is comparable to that of quantitative microbial culture. The increased sensitivity of the QPCR method in detection of virulent R. equi should facilitate rapid and accurate diagnosis of R. equi pneumonia in foals.

Actinomycetales Infections↗

PubMed2004

Evaluation of administration of West Nile virus vaccine to pregnant broodmares.

OBJECTIVE: To determine whether administration of killed West Nile virus vaccine was associated with pregnancy loss among broodmares. DESIGN: Retrospective cohort study. ANIMALS: 595 mares. PROCEDURE: Records of pregnant mares with known vaccination history from 4 farms were reviewed. Information obtained from 595 mares included mare's identification; farm; age; breed; reproductive status; last breeding date; date last known pregnant; vaccination date; age of conceptus at vaccination; vaccination during the early embryonic, early fetal, and late fetal periods; and whether an early embryonic death (EED), early fetal loss (EFL), or late fetal loss (LFL) occurred. The relationships between the dichotomous outcomes of loss (eg, EED, EFL, LFL) and independent categoric variables (eg, vaccination during the early embryonic, early fetal, or late fetal periods) were examined. RESULTS: Vaccination of pregnant mares during any period of gestation was not associated with increased incidence of pregnancy loss. CONCLUSIONS AND CLINICAL RELEVANCE: Many mares are already pregnant at the onset of mosquito season, when mares are more likely to be vaccinated than at other times. Our findings provide evidence that vaccine administration will not compromise pregnancy in horses.

Animals↗

PubMed2004

Evaluation of risk factors associated with development of postoperative ileus in horses.

OBJECTIVE: To determine factors associated with development of postoperative ileus (POI) in horses undergoing surgery for colic. DESIGN: Prospective case-control study. ANIMALS: 251 horses undergoing colic surgery, of which 47 developed POI. PROCEDURE: Signalment, history, clinicopathologic data, pre- and postoperative treatments, lesions, complications, costs, and outcome were recorded for all horses during hospitalization. RESULTS: Variables associated with increased odds of POI included small intestinal lesion, high PCV, and increased duration of anesthesia. There was modest evidence that pelvic flexure enterotomy and intraoperative administration of lidocaine may have reduced the odds of developing POI. CONCLUSIONS AND CLINICAL RELEVANCE: Findings during the preoperative and intraoperative periods can be used to identify horses at increased risk of POI. Reducing surgical and anesthetic duration should decrease the incidence of POI.

Anesthesia↗

PubMed2004

Nramp1 deletion does not confer susceptibility to Rhodococcus equi infection in mice.

Rhodococcus equi is an intracellular bacterium that causes pneumonia in immunocompromised people and foals. The Nramp1 gene influences susceptibility to a variety of intracellular bacteria (including mycobacterial species), but not to Mycobacterium tuberculosis. In this study, we demonstrate that mice functionally deleted of the Nramp1 gene were not more susceptible to infection with virulent R. equi (ATCC 33701) than wild-type mice. Susceptibility of mice to infection with the intracellular bacterium R. equi is more similar to that of M. tuberculosis than to other intracellular bacteria, including other mycobacteria.

Actinomycetales Infections↗

PubMed2004

Hematologic and immunophenotypic factors associated with development of Rhodococcus equi pneumonia of foals at equine breeding farms with endemic infection.

Rhodococcus equi causes severe pyogranulomatous pneumonia in foals and in immunocompromised people. In mice, both CD4+ and CD8+ T lymphocytes contribute to host defense against R. equi, but CD4+ T lymphocytes are required for pulmonary clearance of the bacteria. In this prospective study of 208 foals at two equine breeding farms with endemic R. equi infections, we collected peripheral blood samples at 2 and 4 weeks of age and at the time of diagnosis of R. equi pneumonia. Samples were analyzed for concentrations of total and differential leukocytes, EqCD4+ and EqCD8+ T lymphocytes, and B lymphocytes. Thirty (14.4%) foals developed R. equi pneumonia. At the 2nd week of life, affected foals had significantly lower concentrations of white blood cells (WBC) and segmented neutrophils, significantly lower proportions of EqCD4+ T lymphocytes, and significantly higher proportions of EqCD8+ T lymphocytes. The EqCD4:EqCD8 ratio was significantly lower for affected foals. At the 4th week of life, affected foals had significantly lower concentrations of segmented neutrophils and EqCD4+ T lymphocytes than did unaffected foals. The ratio of EqCD4:EqCD8 was significantly lower for affected foals. Two- and 4-week-old foals with ratios of EqCD4:EqCD8<3 were significantly more likely to develop R. equi pneumonia. There was a significant farm effect which diluted our statistical power to detect differences; however; after adjusting for the farm effect, 2-week-old foals with ratios of EqCD4:EqCD8<3 remained significantly more likely to develop R. equi pneumonia. There were no significant differences in immunophenotypic variables between affected foals (at the time of diagnosis) and age-matched control foals. These data suggest that there are hematologic and immunophenotypic differences between affected and unaffected foals during the first 2-4 weeks of life, prior to onset of clinical signs of R. equi pneumonia. These differences may represent important immunologic mechanisms associated with increased susceptibility of individual foals to infection with R. equi. Because there was considerable overlap between values for affected and unaffected foals, we cannot yet recommend immunophenotyping of foals at endemically-infected farms as a clinically useful screening tool to identify foals at increased risk of developing R. equi pneumonia.

Actinomycetales Infections↗

PubMed2004

Evaluation of urine sucrose concentration for detection of gastric ulcers in horses.

OBJECTIVE: To evaluate the use of sucrose permeability testing to detect ulcers in the gastric squamous mucosa of horses. ANIMALS: 13 adult horses ranging from 5 to 19 years of age. PROCEDURE: Following induction of gastric ulcers by intermittent feed deprivation, horses underwent sucrose permeability testing (administration of sucrose by nasogastric intubation followed by collection of urine at 2 and 4 hours after intubation) and gastric endoscopy. Squamous ulcers were assigned a severity score (range, 0 to 3) by use of an established scoring system. Horses were subsequently administered omeprazole for 21 days, and sucrose testing and endoscopy were repeated. Pair-wise comparisons of urine sucrose concentration were made between horses with induced ulcers before and after omeprazole treatment. Urine sucrose concentrations also were compared on the basis of ulcer severity score. RESULTS: Urine sucrose concentrations and ulcer severity scores were significantly higher in horses with induced ulcers before omeprazole treatment than after treatment. Urine sucrose concentrations were significantly higher for horses with ulcer severity scores > 1. Use of a cut-point value of 0.7 mg/mL revealed that the apparent sensitivity and specificity of sucrose permeability testing to detect ulcers with severity scores > 1 was 83% and 90%, respectively. Results were similar after adjusting sucrose concentrations for urine osmolality. CONCLUSIONS AND CLINICAL RELEVANCE: Urine sucrose concentration appears to be a reliable but imperfect indicator of gastric squamous ulcers in horses. Sucrose permeability testing may provide a simple, noninvasive test to detect and monitor gastric ulcers in horses.

Animals↗