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Biomedical subjects

R W Sweeney

Publications and source records attributed to R W Sweeney.

At least 19 recordsLinked to original sources

Tissue predilection sites and effect of dose on Mycobacterium avium subs. paratuberculosis organism recovery in a short-term bovine experimental oral infection model.

The objective of this study was to develop a short-term experimental infection model for Mycobacterium avium subsp. paratuberculosis (MAP) in cattle, using small oral doses of organisms. Specifically, the effect of dose size was evaluated, as well as specific tissue predilection sites for recovery of MAP. Oral doses as low as 1.5 x 10(6) CFU reliably produced infection that could be detected 3 weeks following infection. Detection of infection required culture of multiple intestinal samples (jejunum and ileum) for MAP. Histological examination did not permit detection at this early stage. Results from this study suggest intestinal mucosa, rather than tonsil, as the primary portal of entry for MAP. The experimental infection model described here is useful for studying the early effects of preventive and therapeutic interventions for paratuberculosis in cattle.

Animals↗

Disposition of flunixin meglumine injectable preparation administered orally to healthy horses.

An injectable preparation of flunixin meglumine was administered orally and intravenously at a dose of 1.1 mg/kg to six healthy adult horses in a cross-over design. Flunixin meglumine was detected in plasma within 15 min of administration and peak plasma concentrations were observed 45-60 min after oral administration. Mean bioavailability of the oral drug was 71.9 +/- 26.0%, with an absorption half-life of 0.76 h. The apparent elimination half-life after oral administration was 2.4 h. The injectable preparation of flunixin meglumine is suitable for oral administration to horses.

Administration, Oral↗

Hypokalaemia as a cause of recumbency in an adult dairy cow.

A 3-year-old Holstein cow was presented for evaluation of recumbency. Physical examination and laboratory evaluations resulted in a diagnosis of hypokalaemia causing extreme skeletal muscle weakness. Treatment involved intravenous and oral potassium supplementation, antimicrobial and anti-inflammatory therapy, and management of recumbency using a flotation tank (the Aquacow Rise System). The cow recovered and returned to the milking herd. Multifactorial elements were identified as the cause of hypokalaemia including inappetance, treatments for ketosis and administration of dexamethasone.

Administration, Oral↗

Evaluation of a commercial ELISA for diagnosis of paratuberculosis in cattle.

OBJECTIVE: To evaluate sensitivity and specificity of a new ELISA for antibodies against Mycobacterium avium subsp paratuberculosis. DESIGN: Cross-sectional observational survey. SAMPLE POPULATION: Serum samples from 590 cattle that were infected with M avium subsp paratuberculosis and 723 cattle that were not infected. PROCEDURE: Serum samples were tested by use of an ELISA for antibodies against M avium subsp paratuberculosis. RESULTS: Sensitivity of the test varied from 15.4 to 88.1%, depending on the clinical stage and bacterial shedding status of the cattle. CONCLUSIONS AND CLINICAL RELEVANCE: Results obtained with use of the new ELISA agreed favorably with those of a previous ELISA. Practitioners must be aware of variability in the sensitivity of the test, which depends on the clinical and shedding status of the cattle, because this may affect interpretation of test results.

Animals↗

ELISA and fecal culture for paratuberculosis (Johne's disease): sensitivity and specificity of each method.

The sensitivity and specificity of the ELISA and fecal culture tests for paratuberculosis in dairy cattle are examined. ELISA and fecal culture data from seven dairy herds where both fecal cultures and ELISA testing was done concurrently are included. A cohort of 954 cattle including 697 parturient adults, cultured every 6 months from 10 herds followed over 4 years served as the basis to determine fecal culture sensitivity. The fecal culture technique utilized a 2g sample with centrifugation and double incubation. Of the 954 cattle cohort of all ages (calf to adult) that were fecal sampled on the first herd visit, 79 were culture positive. An additional 131 animals were detected as culture positive over the next seven tests at 6-month intervals. The sensitivity of fecal culture to detect infected cattle on the first sampling was 38%. Of the 697 parturient cattle cohort, 67 were positive on the first fecal culture, while an additional 91 adult cattle were culture positive over the next seven tests, resulting in a sensitivity of 42% on the first culture of the total animals identified as culture positive. Animals culled from the herds prior to being detected as infected and animals always fecal culture negative with culture positive tissues at slaughter are not included in the calculations. Both groups of infected cattle will lower the apparent sensitivity of fecal culture. Infected dairy herds tested concurrently with both fecal culture and ELISA usually resulted in more than twofold positive animals by culture compared to ELISA. The classification of infected cattle by the extent of shedding of Mycobacterium paratuberculosis in the feces helps define the relative proportion of cattle in each group and therefore the likelihood of detection by the ELISA test. ELISA has a higher sensitivity in animals with a heavier bacterial load, i.e. high shedders (75%) compared to low shedders (15%). Repeated testing of infected herds identifies a higher proportion of low shedders which are more likely to be ELISA negative. Thus, the sensitivity of the ELISA test decreases with repeated herd testing over time, since heavy shedders will be culled first from the herds.

Animals↗

Treatment of potassium balance disorders.

Potassium is the predominant intracellular cation and is critical for the maintenance of resting cellular membrane potential. Abnormalities of potassium balance can manifest as skeletal and cardiac muscle dysfunction. Abnormalities of potassium concentration in plasma can result from changes in external potassium balance (intake vs. excretion) or internal balance (intracellular to extracellular). Hyperkalemia can result from renal failure, uroperitoneum, or severe dehydration and acidosis in calves with diarrhea. Hypokalemia occurs due to reduced forage intake, when increased gastrointestinal losses occur as with diarrhea, due to increased renal losses as with metabolic alkalosis or exogenous corticosteroid administration which promote kaliuresis, or with redistribution of potassium into the intracellular compartment with alkalosis or in association with insulin-mediated glucose uptake. Aggressive intravenous and oral therapy are often necessary to correct potassium balance disorders, in addition to therapy aimed at correcting any underlying disorder contributing to the potassium imbalance.

Animals↗

Evaluation of a rapid reagent strip test for blood glucose determination in diarrheic calves.

Sixty-three blood samples from 10 diarrheic calves were tested for glucose concentration by two methods. Plasma glucose concentration was measured by the conventional glucose-6-phosphate dehydrogenase method in the clinical laboratory, and the results compared to those obtained using a rapid reagent strip test for blood glucose concentration measurement. The rapid reagent strip test result could not be used to make an accurate prediction of the actual plasma glucose concentration as determined by the conventional method, due to the wide variability in actual plasma glucose concentrations corresponding to each rapid test result.

Journal Article↗

Enteric beta-defensin: molecular cloning and characterization of a gene with inducible intestinal epithelial cell expression associated with Cryptosporidium parvum infection.

A growing body of evidence suggests that endogenous antibiotics contribute to the innate defense of mammalian mucosal surfaces. In the cow, beta-defensins constitute a large family of antibiotic peptides whose members have been previously isolated from the respiratory and oral mucosa, as well as circulating phagocytic cells. A novel bovine genomic clone with beta-defensin-related sequence [corrected] related to those of these alpha-defensins was isolated and characterized. The corresponding cDNA was isolated from a small intestinal library; its open reading frame predicts a deduced sequence of a novel beta-defensin, which we designate enteric beta-defensin (EBD). Northern blot analysis of a variety of bovine tissues revealed that EBD mRNA is highly expressed in the distal small intestine and colon, anatomic locations distinct from those for previously characterized beta-defensins. EBD mRNA was further localized by in situ hybridization to epithelial cells of the colon and small intestinal crypts. Infection of two calves with the intestinal parasite Cryptosporidium parvum induced 5- and 10-fold increases above control levels of EBD mRNA in intestinal tissues. An anchored-PCR strategy was used to identify other beta-defensin mRNAs expressed in the intestine. In addition to that of EBD, several low-abundance cDNAs which corresponded to other beta-defensin mRNAs were cloned. Most of these clones encoded previously characterized beta-defensins or closely related isoforms, but two encoded a previously uncharacterized prepro-beta-defensin. Northern blot evidence supported that all of these other beta-defensin genes are expressed at levels lower than that of the EBD gene in enteric tissue. Furthermore, some of these beta-defensin mRNAs were abundant in bone marrow, suggesting that in enteric tissue their expression may be in cells of hematopoietic origin. Extracts of small intestinal mucosa obtained from healthy cows have numerous active chromatographic fractions as determined by an antibacterial assay, and one peptide was partially purified. The peptide corresponded to one of the low-abundance cDNAs. This study provides evidence of beta-defensin expression in enteric tissue and that the mRNA encoding a major beta-defensin of enteric tissue, EBD, is inducibly expressed in enteric epithelial cells. These findings support the proposal that beta-defensins may contribute to host defense of enteric mucosa.

Amino Acid Sequence↗

Interferon-gamma and interleukin 4 gene expression in cows infected with Mycobacterium paratuberculosis.

OBJECTIVE: To determine whether clinical progression of paratuberculosis in cattle was associated with alterations in cytokine gene expression in affected tissues. ANIMALS: 5 uninfected adult Holstein cows, 7 adult Holstein cows naturally infected with Mycobacterium paratuberculosis that did not have clinical signs of disease, and 4 adult Holstein cows naturally infected with M paratuberculosis that had progressive clinical signs of infection. PROCEDURE: Samples of ileum and cecal lymph nodes were obtained from each animal at the time of slaughter. A reverse transcriptase-competitive polymerase chain reaction assay was used to determine mRNA expression of interferon-gamma (IFN-gamma) and interleukin 4 in each sample. RESULTS: Interferon-gamma gene expression was significantly higher in ileum and cecal lymph node samples from subclinically infected cows than from clinically infected cows. CONCLUSIONS AND CLINICAL RELEVANCE: Progression of paratuberculosis to clinical stages is associated with reduced expression of IFN-gamma at site of infection. If immune response to M paratuberculosis can be manipulated so that IFN-gamma expression is increased, resistance to infection in cattle might be enhanced.

Animals↗

Hypokalemia syndrome in dairy cows: 10 cases (1992-1996)

OBJECTIVE: To evaluate clinical findings in cows with recumbency associated with hypokalemia. DESIGN: Retrospective case series. ANIMALS: 10 adult dairy cows with weakness or recumbency and hypokalemia. PROCEDURE: Signalment, history, physical examination findings, results of diagnostic tests, and response to treatment were extracted from the medical record of each cow. RESULTS: 8 cows were recumbent on admission and 2 were profoundly weak. All cows had been given isoflupredone acetate as treatment for ketosis prior to admission. All were hypokalemic (serum potassium concentration, 1.4 to 2.3 mEq/L) with no other apparent cause for recumbency. Despite treatment with potassium, plasma potassium concentrations within the reference range were achieved in only 6 of the 9 cows treated. Two cows responded to treatment. Three cows died, 3 were euthanatized, 2 improved clinically and were discharged, 1 was discharged while still recumbent, and 1 was sent to slaughter prior to treatment. Histologic examination of muscle tissue from 2 cows revealed myonecrosis and vacuolation consistent with hypokalemic myopathy. CLINICAL IMPLICATIONS: Hypokalemia should be considered in the differential diagnosis for cows that are weak or recumbent, particularly after treatment for ketosis with isoflupredone acetate. Aggressive treatment with potassium salts administered orally is indicated.

Administration, Oral↗

Transmission of paratuberculosis.

Infection of the calf soon after birth by oral ingestion of M. paratuberculosis organisms from feces of infected cows is the most important method of transmission of paratuberculosis. The severity and rate of progression of the disease are dependent on the quantity of organisms in the exposure and the age of the animal. Only a small dose of organisms may be required to establish infection in a newborn calf, and overwhelming age-related resistance by introduction of a large dose of organisms to an adult cow is probably possible. Other means of transmission such as transplacental and direct excretion in the milk and colostrum should not be ignored and should be a particular concern primarily in advanced stages of infection when heavy fecal shedding is detected.

Animals↗

Pharmacokinetics of enrofloxacin in adult horses and concentration of the drug in serum, body fluids, and endometrial tissues after repeated intragastrically administered doses.

OBJECTIVE: To investigate the pharmacokinetics of enrofloxacin in adult horses. DESIGN: 2-dose oral and i.v. cross-over trial followed by multiple oral doses. ANIMALS: 8 clinically normal adult horses. PROCEDURE: Enrofloxacin was administered at dosages of 2.5 mg/kg of body weight to 4 horses and 5.0 mg/kg to 4 other horses. Each dose was given by the intragastric and i.v. routes, using a cross-over design. After the first intragastric dose, 5 additional doses were administered at 12-hour intervals. Enrofloxacin concentrations were measured in serum, synovial fluid, peritoneal fluid, urine, CSF, and endometrial tissues. RESULTS: Disposition of enrofloxacin after i.v. administration conformed to a 2-compartment model with an elimination half-life of 5.95 and 6.09 hours for the low and high dose, respectively. After the first intragastric administration, time to peak concentration was 1.0 +/- 0.35 and 1.25 +/- 0.43 hours, and the bioavailability was 57.39 +/- 8/45 and 62.52 +/- 19.65% for the low and high dose, respectively. After multiple intragastric administration, peak serum concentration (at 72 to 96 hours) was 2.62 +/- 0.61 micrograms/ml for the low dose and 5.97 +/- 1.56 micrograms/ml for the high dose. After multiple intragastric doses, synovial fluid, urine, and endometrial tissue concentrations exceeded serum concentrations. Peritoneal fluid and CSF concentrations were lower than serum concentrations. CONCLUSIONS: Computer modeling of the pharmacokinetic variables suggested that a single daily i.v. administered dose of 5.5 mg/kg, or orally administered doses of 7.5 mg/kg every 24 hours or 4.0 mg/kg every 12 hours, would be effective in horses. Additional studies are necessary to confirm the efficacy and safety of these dosages in a clinical setting.

Administration, Oral↗

Use of imipramine hydrochloride for treatment of urospermia in a stallion with a dysfunctional bladder.

An 8-year-old stallion was evaluated because of recurrent urinary tract infections and chronic intermittent urospermia. After extensive diagnostic testing, it was hypothesized that the stallion had a reflex dyssynergia of the bladder and urethral sphincter. Initial attempts to manage the urospermia included semen fractionation, semen collection after voluntary urination, and use of semen extenders. None of these efforts reliably yielded a quality ejaculate. Administration of imipramine hydrochloride (1.2 mg/kg of body weight, PO, 4 hours prior to semen collection) was initiated in an attempt to enhance bladder neck closure during ejaculation. This treatment, combined with voluntary urination prior to ejaculation, resulted in ejaculates containing little or no urine. Using this protocol, 19 of 20 mares bred during the subsequent 2 years became pregnant. By the third year, the bladder dysfunction had progressed, and the urospermia was no longer manageable. Bladder catheterization, followed by manual expression of the bladder per rectum, were necessary prior to each semen collection to obtain a urine-free ejaculate. Three-and-a-half years after initial examination, transitional cell carcinoma of the bladder with metastasis was identified, and the stallion was euthanatized. It is not known whether the transitional cell carcinoma was related to the dysfunctional bladder. Imipramine hydrochloride did not eliminate, but did reduce, the frequency and degree of urospermia in the affected stallion for approximately 2 years.

Abdominal Neoplasms↗

Rostral mandibulectomy for treatment of an ameloblastic fibro-odontoma in a cow.

A 1-year-old polled Hereford heifer was admitted with a mass of the rostral mandibular area that had been observed 17 days earlier. Cytologic examination of fluid aspirated from the mass revealed normal blood. Radiography revealed an expansile, osteolytic mass involving the rostral portion of the mandible. Mineralization of the soft-tissue component was evident. Rostral mandibulectomy was performed to remove the mass in its entirety. The histologic diagnosis was ameloblastic fibro-odontoma. One year after surgery, cosmetic appearance of the mandible was acceptable, and there was no evidence of tumor regrowth. Radiation therapy, cryotherapy, and thermocautery have been recommended in conjunction with surgical excision to prevent tumor regrowth in the oral cavity. Tumor regrowth was not a factor in long-term prognosis in this cow.

Animals↗