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Biomedical subjects

M O'Keeffe

Publications and source records attributed to M O'Keeffe.

At least 19 recordsLinked to original sources
PubMed2006

Evaluation of the Premi Test and comparison with the One-Plate Test for the detection of antimicrobials in kidney.

The Premi Test, a test kit designed for the rapid screening of antimicrobial residues in meat, fish and eggs, was evaluated and compared with the (modified) One-Plate Test, an agar diffusion assay. The performance characteristics described for qualitative, screening methods in Commission Decision 2002/657/EC were used for the evaluation. The Premi Test was found to detect a range of antimicrobials to MRL levels in kidney fluid but to have poorer sensitivity for some antimicrobials such as tetracyclines, sulphonamides, flumequine and streptomycin. The test was found not to be sensitive for the banned antimicrobial chloramphenicol. The One-Plate Test was found to detect most tetracyclines and flumequine to MRL levels but to be less sensitive than the Premi Test for most of the other classes of antimicrobials. Neither test alone provides a comprehensive screening test for antimicrobial residues in kidney at MRL levels. However, the Premi Test is fast, easy to use and rugged and, in combination with other antimicrobial tests, may be used to provide a comprehensive screening system for antimicrobials in tissues.

Animals↗
PubMed2006

Five year follow up of laser in situ keratomileusis for all levels of myopia.

AIMS: To assess the long term refractive and visual outcome of patients who have laser in situ keratomileusis (LASIK) surgery. METHODS: This was a retrospective study of visual and refractive outcome of patients who had LASIK surgery performed in 1998 and 1999. All levels of myopia were included in the study. 49 patients attended for follow up. The main outcome measures were safety, predictability, efficacy, and stability. Postoperative complications and aberrations were also recorded. The mean preoperative spherical equivalent was -4.85. RESULTS: At 2 months postoperatively 67% of eyes were within plus or minus 0.5D of attempted correction with 81% within plus or minus 1.0D. At 5 years postoperatively 60% of eyes were within plus or minus 0.5D of attempted correction with 83% within plus or minus 1.0D. 88% of eyes had a vision of 6/12 or better at 2 months compared to 89% of eyes at 5 years. Best spectacle corrected visual acuity (BSCVA) was unchanged or improved in 51%. No eye lost more than one line of BSCVA. Overall, there was regression towards myopia with a mean change in refraction of -0.5D over the 5 years. As expected, severely myopic patients regressed more with a mean change of -1.06D. However, there was a high level of patient satisfaction with the surgery. CONCLUSION: LASIK surgery offers predictable results in terms of refractive and visual outcome with mild regression in refraction over time.

Adult↗
PubMed2006

Cystoid macular oedema in paediatric aphakia and pseudophakia.

AIM: To assess the incidence of cystoid macular oedema (CMO), following lensectomy, anterior vitrectomy (limbal and pars plicata), and primary posterior capsulorhexis following surgery for congenital and developmental cataract. METHODS: A prospective study was carried out involving 30 eyes (20 children) with cataract. Lensectomy, primary posterior capsulorhexis, and anterior vitrectomy were performed on all eyes. Vitrectomy was performed using either a limbal or pars plicata approach. Fluorescein angiography was carried out 4-7 weeks after surgery. Fluorescein was administered intravenously and visualised using the Retcam. RESULTS: Anterior vitrectomy was carried out via the limbal approach in 12 eyes and, of these, six were implanted with an intraocular lens. The pars plicata approach was carried out in 18 eyes and 10 received an implant. CMO was not detected in any eye. CONCLUSION: CMO was not detected in the early postoperative period irrespective of approach to anterior vitrectomy or presence of an intraocular lens. Intravenous fluorescein angiography was performed without complication.

Aphakia, Postcataract↗
PubMed2004

A case control study to examine the pharmacological factors underlying ventricular septal defects in the North of England.

BACKGROUND: Amphetamine exposure is associated with congenital cardiac abnormalities in animals. We previously reported an association between recreational use of 2,4-methylenedioxymethamphetamine (ecstasy, MDMA) and ventricular septal defect in babies born to users. We have carried out a case control study to investigate risks in the occurrence of ventricular septal defect in a cohort of babies born in the North East of England. METHODS: Cases were identified from paediatric cardiology units in Newcastle upon Tyne and Leeds, and controls were recruited from the mothers of babies born in the same hospital as the index case. Research nurses carried out interviews using a structured questionnaire. RESULTS: A total of 296 case control pairs were studied. There was insufficient exposure to ecstasy to test the primary hypothesis. Increased risk of ventricular septal defect was found to be associated with consumption of cough and cold remedies [pre-conception OR 2.2, 95% CI 1.41, 3.51; pregnancy OR 5.1, 95% CI 2.56, 11.27; exposure in either OR 2.83, 95% CI 1.85, 4.45; P<0.005] and in the case of non-steroidals for exposures in pregnancy (OR 4.2, 95% CI 1.54, 14.26; P<0.005). CONCLUSIONS: These findings suggest that ventricular septal defect is associated with consuming the medications identified. They are also compatible with the hypothesis that sympathomimetics (pseudoephedrine, phenylephrine and phenylpropanolamine) present in cough mixtures cause the increased risk, and with our original hypothesis that sympathomimetics and amphetamines are potentially cardiotoxic in utero.

Adolescent↗
PubMed2004

Application of a modified Oszlányi and Süto ab initio charge-flipping algorithm to experimental data.

The structures of two crystals have been solved using a new iterative phasing method. The iterative phasing algorithm is developed from the 'charge-flipping' method proposed by Oszlányi & Süto [Acta Cryst. (2004), A60, 134-141]. Positivity and point-atom constraints are incorporated within this extremely simple and effective algorithm by flipping (sign reversal) of less-positive density values during the iterations. Convergence is reliably achieved and the two structures were solved. This structure solution method does not require information on atomic scattering factors or symmetry. Heavy atoms can be distinguished from light ones by their charge-density values.

Journal Article↗
PubMed2004

Structural study of new hydrocarbon nano-crystals by energy-filtered electron diffraction.

A new brittle hydrocarbon has been successfully synthesized in polycrystalline form, and its crystal structure solved by quantitative electron diffraction. By 3D tilting of the nano-crystals, the lattice type and unit cell parameters were determined. (Triclinic, [Formula: see text] A, [Formula: see text] A, [Formula: see text] A, [Formula: see text] degrees, [Formula: see text] degrees, and [Formula: see text] degrees.) Spot diffraction patterns were obtained at -165 degrees C using the Koehler selected-area mode on a LEO 912 TEM fitted with an omega in-column elastic energy filter. The direct methods algorithm was then applied to merged intensities and a trial structure obtained assuming single scattering. This was further refined to obtain good agreement with a small residual of about 10% using multiple scattering calculations. A diagram of the proposed structure is given.

Journal Article↗
PubMed2003

Charge density and chemical bonding in rutile, TiO2.

The low-order structure factors of rutile (TiO(2)) have been measured with an accuracy of up to 0.09% by quantitative convergent-beam electron diffraction (QCBED). This error is an order of magnitude smaller than that in conventional Bragg X-ray diffraction and equivalent to the accuracy of the X-ray Pendellösung method. It is sufficient to distinguish atomic, covalent and ionic bonding. By refinement of the combined data of low-order reflections measured by electron diffraction with high-order reflections from X-ray diffraction, accurate charge-density maps are obtained and used to understand the role of the 3d electrons in Ti-O bonding. The results are combined with electron energy-loss spectra (EELS) in a study of the electronic structure.

Journal Article↗
PubMed2003

Preliminary evaluation of a lateral flow immunoassay device for screening urine samples for the presence of sulphamethazine.

A lateral flow immunoassay (LFIA) device was developed and applied to testing urine samples for residues of the antimicrobial sulphamethazine (SMZ). This report describes the preparation of a rat monoclonal antibody to SMZ and its characterisation in an ELISA format. Apart from SMZ, the antibody showed high (> or =50%) cross-reactivity to N4-acetyl-sulphamethazine (55%), sulphamerazine (59%) and sulphisoxazole (50%) and lower cross-reactivity of 18% to sulphachlorpyridazine and sulphadiazine. The LFIA device consisted of a nitrocellulose membrane spotted with SMZ-ovalbumin and goat anti-mouse antibody as capture line and control line, respectively. Mouse anti-rat IgG F(ab')2 fragment specific antibody, adsorbed to colloidal carbon, was used as the detection ligand in the LFIA. The LFIA device had a cut-off value of 6.3 ng/ml in diluted (1/10) urine. Urine samples from SMZ-treated pigs, and bovine and porcine urine samples fortified with SMZ were used for a blind, four-laboratory evaluation of the performance of the LFIA device. Concentrations of SMZ in the test samples (n=29), as determined by LC-MS/MS, ranged from 0 (<3) to 1174 ng/ml. The evaluation of the LFIA device showed an overall sensitivity of 100%, a specificity of 71%, and positive and negative prediction values of 73% and 100%, respectively. The LFIA device has been fabricated as a test kit for determining SMZ residues in animals produced for slaughter.

Animals↗
PubMed2002

Methods for generation of monoclonal antibodies to the very small drug hapten, 5-benzimidazolecarboxylic acid.

Drug-specific monoclonal antibodies (MAbs) were produced against the very small drug hapten (162.15 Da), 5-benzimidazolecarboxylic acid, an analogue of 2-(4-Thiazolyl)benzimidazole (TBZ) but lacking the thiol group. TBZ is widely used as a broad-spectrum anthelmintic in various animal species and humans and also as a food preservative and agricultural fungicide. The anti-5-benzimidazolecarboxylic acid antibodies produced have potential use for extraction and/or detection of protein-bound residue forms of TBZ. Three in vivo immunisation regimes (with combinations of two related small drug haptens and two different adjuvants/carrier molecules) and an in vitro immunisation procedure using a combination of three related unconjugated small drug haptens were investigated. Specificity for the hapten immunogen/s was initially determined using two different ELISA procedures. BIACORE analysis, in conjunction with drug binding inhibition studies, was used to confirm the specificity of a small number of selected clones. In vivo immunisation with a drug molecule conjugated to a lipopeptide/T-cell epitope, which acts both as a carrier molecule and an adjuvant was the most useful of the methods tested for the production of specific MAbs to a typically very small hapten with low immunogenic properties.

Animals↗
PubMed2002

Tumour cell radiosensitization using constitutive (CMV) and radiation inducible (WAF1) promoters to drive the iNOS gene: a novel suicide gene therapy.

Nitric oxide (NO(*)) has many characteristics including cytotoxicity, radiosensitization and anti-angiogenesis, which make it an attractive molecule for use in cancer therapy. We have investigated the use of iNOS gene transfer, driven by both a constitutive (CMV) and X-ray inducible (WAF1) promoter, for generating high concentrations of NO(*) within tumour cells. We have combined this treatment with radiation to exploit the radiosensitizing properties of this molecule. Transfection of murine RIF-1 tumour cells in vitro with the iNOS constructs resulted in increased iNOS protein levels. Under hypoxic conditions cells were radiosensitized by delivery of both constructs so that these treatments effectively eliminated the radioresistance observed under hypoxic conditions. In vivo transfer of the CMV/iNOS construct by direct tumour injection resulted in a delay (4.2 days) in tumour growth compared with untreated controls. This was equivalent to the effect of 20 Gy X-rays alone. Combination of CMV/iNOS gene transfer with 20 Gy X-rays resulted in a dramatic 19.8 day growth delay compared with controls. Tumours treated with the CMV/iNOS showed large areas of necrosis and abundant apoptosis. We believe that iNOS gene transfer has the potential to be a highly effective treatment in combination with radiotherapy.

Animals↗
PubMed2002

Use of solid phase extraction for the isolation and clean-up of a derivatised furazolidone metabolite from animal tissues.

A method is presented for the determination of protein-bound residues of furazolidone in animal tissue. The use of furazolidone in food-producing animals has been banned in the EU. Illegal use of furazolidone can be monitored most effectively by testing for bound residues containing the 3-amino-2-oxazolidone (AOZ) moiety which, unlike the parent drug, is stable and can be detected for prolonged periods after cessation of treatment. This paper reports the development of an extraction and clean-up procedure for AOZ from liver using solid phase extraction. The method replaces solvent extraction and provides extensive sample clean-up with removal of approximately 99% of the derivatising agent, 2-nitrobenzaldehyde, which may interfere with the determination. It also offers the advantage of being suitable for automation, thereby increasing throughput of samples. The extraction procedure may be used for HPLC and ELISA screening techniques. The method has been validated in fortified and incurred pig liver samples, yielding mean recovery of AOZ in excess of 60%.

Animals↗
PubMed2001

Homogeneous cubic cylinder packings revisited.

A method of systematically enumerating homogeneous (i.e. symmetry-related) packings of equal cylinders is developed. 19 three-way packings with axes parallel to <100> and 40 four-way packings with axes parallel to <111> are described. Cubic 6-, 12- and 24-way packings are possible and examples are given with axes parallel to <210> and <421>.

Journal Article↗
PubMed2001

A simple isohedral tiling of three-dimensional space by infinite tiles and with symmetry Ia(-)3d.

A tiling of space by tiles that have all hexagonal faces and are infinite in one direction is described. The tiling is simple (four tiles meet at each vertex, three at each edge and two at each face) and carries a 4-connected net whose vertices are the lattice complex S* with symmetry Ia(-)3d. The tiling is closely related to the densest cubic cylinder packing, Gamma. It is shown that the other invariant cubic lattice complexes unique to Ia(-)3d (Y** and V*) are also related to the same cylinder packing.

Journal Article↗
PubMed2001

Development of thymic and splenic dendritic cell populations from different hemopoietic precursors.

The antigen-presenting dendritic cells (DCs) found in mouse lymphoid tissues are heterogeneous. Several types of DCs have been identified on the basis of the expression of different surface molecules, including CD4, CD8alpha, and DEC-205. Previous studies by the authors showed that the mouse intrathymic lymphoid-restricted precursors (lin(-)c-kit(+)Thy-1(low)CD4(low)) can produce DCs in the thymus and spleen upon intravenous transfer, suggesting a lymphoid origin of these DCs. In the current study, the potential for DC production by the newly identified bone marrow (BM) common lymphoid precursors (CLPs), common myeloid precursors (CMPs), and committed granulocyte and macrophage precursors was examined. It was found that both the lymphoid and the myeloid precursors had the potential to produce DCs. All the different DC populations identified in mouse thymus and spleen could be produced by all these precursor populations. However, CLPs produced predominantly the CD4(-)CD8alpha(+) DCs, whereas CMPs produced similar numbers of CD4(-)CD8alpha(+) and CD4(+)CD8alpha(-) DCs, although at different peak times. On a per cell basis, the CLPs were more potent than the CMPs at DC production, but this may have been compensated for by an excess of CMPs over CLPs in BM. Overall, this study shows that the expression of CD8alpha does not delineate the hemopoietic precursor origin of DCs, and the nature of the early precursors may bias but does not dictate the phenotype of the DC product.

Animals↗
PubMed2001

Evidence of 29Si NMR paramagnetic shifts in rare-earth zeolite LSX.

Paramagnetic shifts have been observed for the first time in rare-earth zeolites; the 29Si MAS NMR spectra of rare-earth ion-exchanged low silica X show a large range of isotropic chemical shifts that can be attributed to Fermi contact interactions with the lanthanide electronic moments.

Journal Article↗
PubMed2001

c-Rel regulates interleukin 12 p70 expression in CD8(+) dendritic cells by specifically inducing p35 gene transcription.

Interleukin 12 (IL-12) is a 70-kD proinflammatory cytokine produced by antigen presenting cells that is essential for the induction of T helper type 1 development. It comprises 35-kD (p35) and 40-kD (p40) polypeptides encoded by separate genes that are induced by a range of stimuli that include lipopolysaccharide (LPS), DNA, and CD40 ligand. To date, the regulation of IL-12 expression at the transcriptional level has mainly been examined in macrophages and restricted almost exclusively to the p40 gene. Here we show that in CD8(+) dendritic cells, major producers of IL-12 p70, the Rel/nuclear factor (NF)-kappaB signaling pathway is necessary for the induction of IL-12 in response to microbial stimuli. In contrast to macrophages which require c-Rel for p40 transcription, in CD8(+) dendritic cells, the induced expression of p35 rather than p40 by inactivated Staphylococcus aureus, DNA, or LPS is c-Rel dependent and regulated directly by c-Rel complexes binding to the p35 promoter. This data establishes the IL-12 p35 gene as a new target of c-Rel and shows that the regulation of IL-12 p70 expression at the transcriptional level by Rel/NF-kappaB is controlled through both the p35 and p40 genes in a cell type-specific fashion.

Animals↗