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Biomedical subjects

C Kearns

Publications and source records attributed to C Kearns.

9 recordsLinked to original sources
PubMed2003

Evaluation of an absorbed ELISA and an agar-gel immuno-diffusion test for ovine paratuberculosis in sheep in Australia.

The sensitivities and specificities of an absorbed enzyme-linked immunosorbent assay (ELISA) and an agar-gel immuno-diffusion (AGID) test for the detection of Johne's disease in sheep were estimated using data from six known infected and 12 assumed uninfected sheep flocks. Sensitivities were estimated for all histologically positive sheep, as well as by histological lesion score, lesion type (paucibacillary or multibacillary) and sheep body-condition score, with ELISA sensitivities estimated at 95 and 99% specificity. Logistic-regression analysis was used to test for significant effects of lesion score and condition score, with flock included in the model as a random effect. Estimated specificities were 95% (95% CI: 93.4, 95.6%) and 99% (98.4, 99.4%) for ELISA cut-point ratios of 2.4 and 3.6, respectively, and 100% (99.7, 100.0%) for the AGID. Estimated sensitivities for all infected sheep were 41.5% (35.0, 48.3%), 21.9% (16.6, 27.9%) and 24.6% (19.1, 30.7%) for ELISA cut-point ratios of 2.4 and 3.6 and for AGID, respectively. Sensitivities of all tests and cut-points varied significantly between flocks and between categories of lesion score and condition score. Sensitivity ranged from 25 to 73, 10 to 47 and 9.2 to 63% between flocks, for the ELISA with cut-points of 2.4 and 3.6, and for the AGID, respectively. Sensitivity was highest in thin sheep and in sheep with multibacillary lesions. The effects of lesion type and condition score on test sensitivity were significant in the logistic regressions for the AGID and ELISA at both cut-points and the flock effect was significant for the AGID but not for the ELISA at either cut-point.

Animals↗
PubMed2001

Leveling the playing field for EMS services.

Pinellas County's emergency medical services system is a public utility model EMS system where as the purchaser of services, the EMS Authority can achieve the highest-quality, most cost-effective and most reliable EMS services. Pinellas County's use of an absolute level-playing-field, non-political bidding process that isolated quality and pricing issues has raised the bar for government purchasing. The entire EMS industry has seen how contract services can be evaluated fairly, in a non-political atmosphere, for the betterment of the citizens of the community. Our EMS Authority voted to award the contract to the best overall proposal based on fact and merit. The new agreement allows us to provide significantly improved paramedic ambulance services to our citizens at a substantial cost reduction to the county.

Competitive Bidding↗
PubMed1999

Further observations on the epidemiology and spread of epizootic haematopoietic necrosis virus (EHNV) in farmed rainbow trout Oncorhynchus mykiss in southeastern Australia and a recommended sampling strategy for surveillance.

Epizootic haematopoietic necrosis virus (EHNV) is an iridovirus confined to Australia and is known only from rainbow trout Oncorhynchus mykiss and redfin perch Perca fluviatilis. Outbreaks of disease caused by EHNV in trout populations have invariably been of low severity, affecting only 0+ post-hatchery phase fingerlings < 125 mm in length. To date the virus has been demonstrated in very few live in-contact fish, and anti-EHNV antibodies have not been found in survivors of outbreaks, suggesting low infectivity but high case fatality rates in trout. During an on-going study on an endemically infected farm (Farm A) in the Murrumbidgee River catchment of southeastern New South Wales, EHNV infection was demonstrated in 4 to 6 wk old trout fingerlings in the hatchery as well as in 1+ to 2+ grower fish. During a separate investigation of mortalities in 1+ to 2+ trout on Farm B in the Shoalhaven River catchment in southeastern New South Wales, EHNV infection was demonstrated in both fingerlings and adult fish in association with nocardiosis. A 0.7% prevalence of antibodies against EHNV was detected by ELISA in the serum of grower fish at this time, providing the first evidence that EHNV might not kill all infected trout. EHNV infection on Farm B occurred after transfer of fingerlings from Farm C in the Murrumbidgee river catchment. When investigated, there were no obvious signs of diseases on Farm C. 'Routine' mortalities were collected over 10 d on Farm C and EHNV was detected in 2.1% of 190 fish. Tracing investigations of sources of supply of fingerlings to Farm B also led to investigation of Farm D in Victoria, where the prevalence of anti-EHNV antibodies in 3+ to 4+ fish was 1.3%. The results of this study indicate that EHNV may be found in trout in all age classes, need not be associated with clinically detectable disease in the population, can be transferred with shipments of live fish, can be detected in a small proportion of 'routine' mortalities and may be associated with specific antibodies in a small proportion of older fish. Sampling to detect EHNV for certification purposes should be based on examination of 'routine' mortalities rather than random samples of live fish. Antigen-capture ELISA can be used as a cost effective screening test to detect EHNV on a farm provided that sampling rates conform with statistical principles.

Animals↗
PubMed1997

Detection of antibodies against iridoviruses in the serum of the amphibian Bufo marinus.

Sera from the amphibian Bufo marinus (cane or marine toad) were investigated using a newly-developed enzyme-linked immunosorbent assay for the detection of antibodies to ranaviruses (Family Iridoviridae). Epizootic haematopoietic necrosis virus (EHNV) or Bohle iridovirus (BIV) was affinity purified from cell culture supernatants and simultaneously bound to the solid phase using specific linker antibodies. After binding to antigen, antibodies in Bufo marinus serum were then detected with a specific anti-immunoglobulin reagent. Of 21 Bufo marinus sera, 3 contained antibodies against EHNV, BIV or related viruses in the ranavirus group, at titres greater than 3200. Reactivity of cane toad antibodies against BIV, an amphibian virus, was greater than that against similar concentrations of EHNV, a piscine virus.

Animals↗
PubMed1995

Feasibility and pharmacokinetics of paclitaxel, carboplatin, and concurrent radiotherapy for regionally advanced squamous cell carcinoma of the head and neck and for regionally advanced non-small cell lung cancer.

Sequential chemotherapy and radiotherapy offer considerable improvements in the care of patients with locally advanced non-small cell lung cancer (NSCLC) and squamous cell carcinoma of the head and neck (SCCHN). Improved survival for lung cancer and organ preservation in head and neck cancer have occurred with this approach, but local control remains a problem. Concurrent chemotherapy and radiotherapy can potentially improve both local control and control of micrometastases. We previously showed that concurrent carboplatin plus radiotherapy is a useful potential treatment for advanced NSCLC and SCCHN, producing good local control and acceptable toxicity. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has recently demonstrated strong single-agent activity against both NSCLC and SCCHN. Paclitaxel has also shown favorable interactions with radiotherapy and with platinum compounds. We therefore added weekly paclitaxel at 45 mg/m2 given after premedication and before carboplatin (100 mg/m2) weekly during concurrent standard-dose radiotherapy. Twenty patients (seven with SCCHN and 13 with NSCLC) have been treated (38 and 73 weekly doses, respectively). Toxicities have been manageable with delay or dose reduction in five and eight patients, respectively, for SCCHN and NSCLC. Based on these toxicities paclitaxel dose has been reduced to 40 mg/m2/wk. Plasma pharmacokinetics have shown that concurrent carboplatin and radiotherapy do not alter the pharmacokinetic behavior of paclitaxel compared with single-agent data. Concurrent therapy with carboplatin, paclitaxel, and radiotherapy is feasible on this schedule. Further case accrual to assess efficacy is ongoing.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Clinical pharmacokinetics and pharmacodynamics of anticancer drugs in children.

Pharmacokinetic variability in children with cancer is substantial and confounds drawing conclusions regarding optimal therapy based only on dose-response relationships. Careful pharmacokinetic studies performed during drug development in conjunction with an assessment of patient characteristics, such as age, renal and hepatic function, and concomitant therapy, is essential for defining those factors that may alter drug disposition. By integrating pharmacokinetic studies with measures of efficacy and toxicity, a pharmacodynamic framework can be established for guiding therapy to minimize differences in systemic exposure among subpopulations of patients (eg, impaired renal function and neonates). In selected instances when pharmacokinetic variability cannot be predicted by patient covariates, the potential for individualizing dosages based on patient-specific pharmacokinetic parameters is now a clinically feasible option. The need for and benefits of incorporating such strategies into routine therapy represents an exciting area for further clinical research.

Adult↗
PubMed1992

2-Chlorodeoxyadenosine produces a high rate of complete hematologic remission in relapsed acute myeloid leukemia.

PURPOSE: The purine analog 2-chlorodeoxyadenosine (2-CDA) was well tolerated and showed promising anti-leukemic activity in a phase I trial conducted at St Jude Children's Research Hospital. To substantiate and extend this result, we performed a phase II trial in a representative group of children and young adults with relapsed acute leukemia. PATIENTS AND METHODS: Twenty-four patients (median age, 11 years) with acute myeloid or lymphoid leukemia in first or later relapse (acute myeloid leukemia [AML], 17; acute lymphoid leukemia [ALL], seven) were given continuous infusion 2-CDA for 5 days at 8.9 mg/m2/d. Patients with residual blast cells 10 days after treatment received a second course of 2-CDA that was identical to the first. Detailed pharmacokinetic studies were performed on plasma collected from five patients. RESULTS: Eight (47%) of the 17 patients with AML had complete hematologic remissions (four after the initial course of 2-CDA), and two (12%) had partial remissions, for a total response rate of 59%. Only one child with ALL achieved remission. Seven of the responding patients underwent allogeneic or autologous bone marrow transplantation, with six remaining free of leukemia for a median of 7 months (range, 1 to 11 months). The major form of drug-induced toxicity was hematologic, with severe neutropenia and thrombocytopenia (National Cancer Institute [NCI] grade 3 or 4) developing in 34 of the 36 courses of 2-CDA. In responding patients, the median times to recovery of neutrophil counts greater than 0.5 x 10(9)/L and platelet counts greater than 50 x 10(9)/L were 18 and 21 days, respectively. There were no deaths due to toxicity. The mean steady-state plasma concentration of 2-CDA was 34.6 nmol/L (range, 20 to 54 nmol/L). CONCLUSION: 2-CDA given by prolonged continuous infusion has clinically significant activity against AML and merits further testing in multidrug regimens for this disease.

2-Chloroadenosine↗