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Biomedical subjects

D Keen

Publications and source records attributed to D Keen.

10 recordsLinked to original sources
PubMed2005

Oral vaccination of brushtail possums (Tichosurus vulpecula) with BCG: immune responses, persistence of BCG in lymphoid organs and excretion in faeces.

AIMS: To determine immune responses, and the localisation and persistence of Mycobacterium bovis bacille Calmette-Guérin (BCG) in gut-associated lymphoid tissues (GALT) and other organs in possums vaccinated orally with lipid-formulated BCG vaccine. To determine the duration of excretion and longevity of survival of BCG in the faeces of vaccinated animals. METHODS: Possums (n=28) were vaccinated with lipid-formulated BCG (1 x 10(8) colony forming units (cfu) of formulated BCG) by the oral route. Control possums (n=17) were fed oral bait pellets containing formulation medium only. Possums were sacrificed at 3 days and at 1, 3, 6 and 8 weeks after vaccination or ingestion of bait. Proliferation responses to bovine purified protein derivative (PPD) were measured in lymphocytes from blood and mesenteric lymph nodes (MLN) and samples of lung, spleen, liver, MLN and Peyer's patches (PP) were cultured for the presence of BCG. The number of BCG organisms excreted in faeces and the duration of excretion were determined in eight vaccinated possums and eight control possums over a 3-week period. In a separate experiment, a further six possums were vaccinated with oral BCG vaccine (5-10 x 10(8) cfu BCG/possum) and their faeces collected over 48-72 h, for culture of BCG. The longevity of survival of BCG in these faeces was determined by storing faecal samples (n=12) under three different conditions: in an incubator (22.5 degrees C), and conditions which simulated the forest floor and open pasture. A proportion (1-2 g) of these faecal samples was collected after storage for 1, 3, 5, 8 or 20 weeks, and cultured for BCG. RESULTS: Possums vaccinated orally with BCG vaccine showed strong proliferation responses to bovine PPD in peripheral blood lymphocytes at 6-8 weeks post-vaccination (p.v.). Positive lymphocyte proliferation assay (LPA) responses to bovine PPD were first evident in MLN at 3 weeks p.v. BCG was cultured from MLN and PP in a proportion of animals at 3-8 weeks p.v. BCG was not cultured from sections of spleen, lung or liver at any time p.v. BCG was recovered in low to moderate numbers from the faeces of vaccinated possums for up to 7 days, and maximal numbers were cultured in faeces collected 48-72 h p.v. After storage for 1 week, BCG was cultured from all faecal samples placed in the incubator and from a proportion of faeces exposed to conditions similar to those on the forest floor and pasture. With the exception of one faecal sample stored under forest floor conditions which was culture-positive for BCG at 3 and 5 weeks, BCG was not cultured from any other faecal sample stored for more than 1 week. CONCLUSIONS: Ingestion of oral BCG vaccine by possums was associated with the development of strong cell-mediated immunity in both blood and MLN. Following oral vaccination with BCG, the organisms were localised and persisted in GALT but did not spread to the spleen, liver or lungs. BCG was shed in low to moderate numbers in the faeces for up to 7 days p.v. The viability of BCG excreted in faeces decreased rapidly, particularly when faeces were exposed to an open pasture environment. Oral vaccination of possums with formulated BCG is unlikely to result in undue contamination of the environment with BCG.

Adjuvants, Immunologic↗
PubMed2001

Replacing prelinguistic behaviors with functional communication.

This study evaluated the effectiveness of a teacher-implemented intervention package designed to replace prelinguistic behaviors with functional communication. Four young children with autism participated in a multiple-probe design across three communicative functions. Initially, three existing communication functions were selected for each child. Next, the existing prelinguistic behaviors that the children used to achieve these functions were identified. Replacement forms that were considered more recognizable and symbolic were defined to achieve these same functions. After a baseline phase, teachers received inservice training, consultation, and feedback on how to encourage, acknowledge, and respond to the replacement forms. During intervention, the replacement forms increased and prelinguistic behaviors decreased in most cases. The results suggested that the teacher-implemented intervention was effective in replacing prelinguistic behaviors with alternative forms of functional communication.

Autistic Disorder↗
PubMed2000

Cereal crops as viable production and storage systems for pharmaceutical scFv antibodies.

This report describes the stable expression of a medically important antibody in the staple cereal crops rice and wheat. We successfully expressed a single-chain Fv antibody (ScFvT84.66) against carcinoembryonic antigen (CEA), a well characterized tumor-associated marker antigen. scFv constructs were engineered for recombinant antibody targeting to the plant cell apoplast and ER. Up to 30 microg/g of functional recombinant antibody was detected in the leaves and seeds of wheat and rice. We confirmed that transgenic dry seeds could be stored for at least five months at room temperature, without significant loss of the amount or activity of scFvT84.66. Our results represent the first transition from model plant expression systems, such as tobacco and Arabidopsis, to widely cultivated cereal crops, such as rice and wheat, for expression of an antibody molecule that has already shown efficacy in clinical applications. Thus, we have established that molecular pharming in cereals can be a viable production system for such high-value pharmaceutical macromolecules. Our findings provide a strong foundation for exploiting alternative uses of cereal crops both in industrialized and developing countries.

Animals↗
PubMed1998

Aid and violence, with special reference to Sierra Leone.

This paper looks at how departures from humanitarian principles can be accommodated, legitimised and obscured within the international humanitarian system. It looks particularly at the case of Sierra Leone between 1991 and 1995. It analyses how misinformation about the causes and dynamics of violence and regarding the aid system contribute to the erosion of humanitarian principles.

Altruism↗
PubMed1995

Protection of cattle from bovine tuberculosis by vaccination with BCG by the respiratory or subcutaneous route, but not by vaccination with killed Mycobacterium vaccae.

Groups of cattle were vaccinated either with BCG Pasteur by the intratracheal or subcutaneous route or with killed Mycobacterium vaccae by the intradermal route and challenged intratracheally 54 days later with Mycobacterium bovis. Vaccination with BCG resulted in fewer animals developing tuberculous lesions and in a reduction in the number of lesions in the diseased animals compared with the unvaccinated group and the group vaccinated with M vaccae. None of the nine animals vaccinated intratracheally with BCG developed any tuberculous lung lesions after challenge with M bovis, but two of the nine animals from each of the groups dosed subcutaneously with low and medium doses of BCG developed lung lesions. There was little difference in protection against the M bovis challenge between the animals receiving the low dose (10(3) colony forming units, cfu) or medium dose (10(5) cfu) of subcutaneous BCG, but the medium dose of BCG produced stronger cell-mediated immune responses to bovine purified protein derivative (PPD) after vaccination. Vaccination intradermally with 10(9) heat-killed M vaccae did not protect cattle against an experimental challenge with M bovis and induced only weak cell-mediated immune responses to bovine PPD.

Animals↗
PubMed1995

Effectiveness of BCG vaccination in protecting possums against bovine tuberculosis.

Three groups of eight possums were vaccinated with BCG Pasteur by the subcutaneous, intratracheal or intragastric routes, with a fourth group serving as unvaccinated controls. Forty-two days after the start of vaccination, five possums from each group were challenged intratracheally with virulent Mycobacterium bovis. The vaccination by the subcutaneous or intratracheal routes resulted in a marked reduction in the severity of disease compared with the unvaccinated animals or the animals vaccinated intragastrically. The severity of the disease was assessed by changes in bodyweight, pathological changes in the lungs and bronchial nodes and the number of acid-fast bacilli in the lesions. Before the challenge, lymphocyte blastogenic responses to bovine PPD were observed in the eight animals vaccinated subcutaneously and in two of the animals vaccinated intratracheally.

Animals↗
PubMed1993

Developing and empowering quality teams.

The authors' radiology department recently found that assorted problems had accumulated over time into a long to-do list. Mr. Keen and Ms. Fegley describe the process they followed to implement continuous quality improvement and develop task force teams to address particular problems.

Academic Medical Centers↗
PubMed1991

Factors driving costs must figure into reform.

Employers and employees seeing their health plan premium costs rise faster than physician and hospital costs is one indication that the U.S. healthcare system is in a state of crisis. Examining factors behind providers' and health plans' costs--demographics, increased hospital expenses, insurance overhead, fragmentation among managed care plans, and failure of some cost-containment initiatives--indicates the shape healthcare reform must take if it is to succeed. Reform proposals in the 1990s likely will entail simplification and consolidation, such as providing universal access, consolidating managed care, and establishing a single-payer system.

Canada↗
PubMed1986

Oral 6-mercaptopurine in childhood leukemia: parent drug pharmacokinetics and active metabolite concentrations.

6-Mercaptopurine (6MP) pharmacokinetics and red blood cell 6-thioguanine nucleotide (TGN) concentrations were studied in 19 children receiving remission maintenance treatment for lymphoblastic leukemia. There was a high interpatient variation in all the pharmacokinetic parameters measured. The pharmacokinetic parameters measured in two children who subsequently had relapses were within the 95% confidence limits of the 17 other children. There was no difference in 6MP pharmacokinetic parameters with respect to neutropenia either after or before the study. The children who developed neutropenia 10 to 19 days after study had significantly higher TGN concentrations (U = 8; P less than 0.001) and had spent a longer time receiving reduced 6MP dosage in the 12 weeks before the study (U = 19.5; P less than 0.025). TGN concentrations are a better index of a child's ability to form active cytotoxic metabolites than 6MP dose or plasma concentrations.

Administration, Oral↗