Northern Ireland Primary and Secondary Care Opioid Substitute Treatment Guidelines 2013 (PDF 4.5MB)

Drugs misuse

CMO Annual Report 2010 (PDF 4.43 MB)

Chief Medical Officer Annual Report 2010

A recyclable assay to analyze the NH(2)-terminal trimming of antigenic peptide precursors.

The proteasome plays an essential role in the production of MHC class I-restricted antigenic peptides. Recent results have indicated that several peptidases, including tripeptidyl peptidase II and puromycin-sensitive aminopeptidase, could act downstream of the proteasome by trimming NH(2)-terminal extensions of antigenic peptide precursors liberated by the proteasome. In this study, we have developed a solid-phase peptidase assay that allowed us to efficiently purify and immobilize proteasome, tripeptidyl peptidase II, and puromycin-sensitive aminopeptidase. Whereas the first peptidase was active against small fluorogenic peptides, the latter two could also digest antigenic peptide precursors and could be used repeatedly with different precursors. Using three distinct antigenic peptide precursors, we found that tripeptidyl peptidase II never cleaved within the antigenic peptide sequence, suggesting that, aside from its proteolytic activities, it may also play a role in protecting antigenic peptides from complete hydrolysis in the cytosol. This method should be valuable for high throughput screenings of substrate specificity and potential inhibitors.

Determination of 13C/12C ratios of endogenous urinary 5-amino-imidazole-4-carboxamide 1-D-ribofuranoside (AICAR)

RATIONALE: AICAR (5-aminoimidazole-4-carboxamide 1β-D-ribofuranoside) is prohibited in sport according to rules established by the World Anti-Doping Agency. Doping control laboratories identify samples where AICAR abuse is suspected by measuring its urinary concentration and comparing the observed level with naturally occurring concentrations. As the inter-individual variance of urinary AICAR concentrations is large, this approach requires a complementary method to unambiguously prove the exogenous origin of AICAR. Therefore, a method for the determination of carbon isotope ratios (CIRs) of urinary AICAR has been developed and validated. METHODS: Concentrated urine samples were fractionated by means of liquid chromatography for analyte cleanup. Derivatization of AICAR yielding the trimethylsilylated analog was necessary to enable CIR determinations by gas chromatography/combustion/isotope ratio mass spectrometry. The method was tested for its repeatability and stability over time and a linear mixing model was applied to test for possible isotopic discrimination. A reference population of n = 63 males and females was investigated to calculate appropriate reference limits to differentiate endogenous from exogenous urinary AICAR. These limits were tested by an AICAR elimination study. RESULTS: The developed method fulfills all the requirements for adequate sports drug testing and was found to be fit for purpose. The investigated reference population showed a larger variability in the CIR of AICAR than of the endogenous steroids. Nevertheless, the calculated thresholds for differences between AICAR and endogenous steroids can be applied straightforwardly to evaluate suspicious doping control samples with the same statistical confidence as established e.g. for testosterone misuse. These thresholds enabled the detection of a single oral AICAR administration for more than 40 h. CONCLUSIONS: Determination of thee CIRs is the method of choice to distinguish between an endogenous and an exogenous source of urinary AICAR. The developed method will enable investigations into doping control samples with elevated urinary concentrations of AICAR and clearly differentiate between naturally produced/elevated and illicitly administered AICAR.

Eficacia de la 4-aminopiridina en el tratamiento de pacientes diagnosticados de ataxia con downbeat nystagmus de causa idiopática

L'atàxia amb downbeat nystamgus (ADBN) es una síndrome clínica que cursa amb atàxia vestíbulo-cerebel•losa i downbeat nystagmus. Es va valorar la seguretat i eficàcia del bloquejador de canal de potassi 4-aminopiridina (4-AP) pel tractament d'aquesta entitat. Es varen incloure nou pacients, es va realitzar una avaluació basal i visites mensuals fins als 90 dies. El fàrmac va ser ben tolerat. El 33% dels pacients van presentar milloria objectiva a l'escala de l'equilibri de Berg i el 66% milloria subjectiva i major autonomia. El nombre total de caigudes va disminuir desde 13 fins a 1. La 4-AP millora l'equilibri en pacients amb ADBN.

Regional Advisory Committee on Cancer - Report on Oesophageal Cancer 2000 (PDF 4.0 Mb)

Regional Advisory Committee on Cancer - Report on Oesophageal Cancer 2000 (pdf 4000Kb)

Assessing multiple sclerosis activity: is the in vitro production of tumor necrosis factor-alpha, interleukins 2, 6, 4, and 10, and immunoglobulin G of value?

Tumor necrosis factor (TNF) alpha, interleukins (IL) 2, 4, 6, and 10, and IgG oligoclonal bands (IgG OB) in vitro production was assessed, after whole-blood stimulation with lipopolysaccharide or concanavalin A, in 61 patients presenting with relapsing-remitting, relapsing-progressive, or chronic progressive multiple sclerosis. Multiple sclerosis patients were receiving no treatment or azathioprine (AZA), cyclosporin, cyclophosphamide, subcutaneous interferon (IFN) beta 1 a, or corticosteroids (CST). Statistical correlations significantly showed that: (a) AZA lowers TNF-alpha (P = 0.002) and increases IL-4 production (P = 0.0024), and IFN-beta 1 a increases TNF-alpha and decreases IL-4 levels; (b) CST has a negative effect on TNF-alpha, IL-6, and IL-4 synthesis; and (c) AZA, IFN-beta 1 a, and CST diminish IgG OB synthesis (P = 0.001). Although our study of the dynamics of TNF-alpha, IL-2, IL-4, IL-6, and IL-10 in vitro production generally found no statistically significant correlations (partly explained by the limited number of values in the various groups), IL-6 was shown to drop during the periods surrounding relapse (P = 0.05) in the absence of treatment, while TNF-alpha (P = 0.04) and IL-6 (P < 0.05) dropped before exacerbation in the presence of AZA. In vitro production of TNF-alpha was closely and positively correlated with that of IL-6, independently of clinical features. The enhanced production of IL-10 detected before or at relapse with AZA and IFN-beta 1 a (trends) may interfere with initiation of the immune reaction and with the development of new CNS lesions. Some discrepancies with previously published results stress the difficulties in studying the state of stimulation of different populations of leukocytes by using a variety of in vitro stimuli and in establishing a correlation between mRNA studies and the amount of final or active protein produced.

Interleukin-4 production in BALB/c mice immunized with Anisakis simplex

We investigated the interleukin (IL-4) levels in BALB/c mice immunized with Anisakis extract in single or multiple doses and in mice orally infected with a larva. From animals immunized maximum responses were obtained with the multiple doses with an only IL-4 peak. Conversely, in the mice inoculated with a larva per os, the IL-4 levels showed two peaks of different rates.

Implantación del distintivo de garantía de calidad ambiental en hoteles de 3*, 4* y 5* de Sitges

Este proyecto tiene como objetivo estudiar la viabilidad de la implantación del Distintivo de Garantía de Calidad Ambiental (DGQA) en los hoteles de 3*, 4* y 5* del municipio de Sitges, perteneciente a la comarca del Garraf. El criterio de selección se ha basado en el estado del hotel (abierto o cerrado) en que se encontraba en el momento del estudio. Para conocer la gestión ambiental de los establecimientos hoteleros se llevó a cabo la realización de unas encuestas elaboradas a partir de los criterios requeridos por el DGQA, tanto obligatorios como opcionales. Los resultados obtenidos muestran un elevado cumplimiento de la puntuación obligatoria, así como la totalidad de los criterios opcionales requeridos. No se han detectado diferencias significativas entre las tres categorías hoteleras. Sin embargo, sí que aparecen diferencias entre los ámbitos propuestos por el DGQA, destacando el elevado cumplimiento en integración paisajística, ruidos y vibraciones, y diseño de espacios exteriores. Por el contrario se observa una carencia relevante en los ámbitos de compras y residuos. Finalmente se han propuesto las acciones de mejora necesarias para dicha obtención, obteniendo así un presupuesto aproximado para la consecución del distintivo por cada uno de los hoteles.

Iterative reconstruction methods in two different MDCT scanners: Physical metrics and 4-alternative forced-choice detectability experiments - A phantom approach.

This paper characterizes and evaluates the potential of three commercial CT iterative reconstruction methods (ASIR?, VEO? and iDose(4 ()?())) for dose reduction and image quality improvement. We measured CT number accuracy, standard deviation (SD), noise power spectrum (NPS) and modulation transfer function (MTF) metrics on Catphan phantom images while five human observers performed four-alternative forced-choice (4AFC) experiments to assess the detectability of low- and high-contrast objects embedded in two pediatric phantoms. Results show that 40% and 100% ASIR as well as iDose(4) levels 3 and 6 do not affect CT number and strongly decrease image noise with relative SD constant in a large range of dose. However, while ASIR produces a shift of the NPS curve apex, less change is observed with iDose(4) with respect to FBP methods. With second-generation iterative reconstruction VEO, physical metrics are even further improved: SD decreased to 70.4% at 0.5 mGy and spatial resolution improved to 37% (MTF(50%)). 4AFC experiments show that few improvements in detection task performance are obtained with ASIR and iDose(4), whereas VEO makes excellent detections possible even at an ultra-low-dose (0.3 mGy), leading to a potential dose reduction of a factor 3 to 7 (67%-86%). In spite of its longer reconstruction time and the fact that clinical studies are still required to complete these results, VEO clearly confirms the tremendous potential of iterative reconstructions for dose reduction in CT and appears to be an important tool for patient follow-up, especially for pediatric patients where cumulative lifetime dose still remains high.

Different epitopes of the LACK protein are recognized by V beta 4 V alpha 8 CD4+ T cells in H-2b and H-2d mice susceptible to Leishmania major.

After inoculation of Leishmania major, a rapid production of IL-4 by LACK-specific CD4+ T cells has been shown to drive Th2 cell development in susceptible mice i.e. BALB/c and C57BL/6 mice rendered susceptible by neutralization of IFN-gamma at the onset of infection. Here, we showed that peptide AA 156-173 induced an early IL-4 mRNA expression not only in BALB/c mice but also in resistant B10.D2 mice when IFN-gamma is neutralized. Epitope mapping of LACK protein demonstrated that peptide containing AA 293-305 induced early IL-4 mRNA transcripts in susceptible H-2b mice i.e. BALB/b and resistant C57BL/6 mice when IFN-gamma is neutralized. Stringently, the early IL-4 response to the H-2d (AA 156-173) or the H-2b (AA 293-305) epitopes occurred in V beta 4 V alpha 8 CD4+ T cells from either H-2d or H-2b susceptible mice, respectively.

Search for Borrelia sp. in ticks collected from potential reservoirs in an urban forest reserve in the State of Mato Grosso do Sul, Brazil: a short report

A total of 128 ticks of the genus Amblyomma were recovered from 5 marsupials (Didelphis albiventris) - with 4 recaptures - and 17 rodents (16 Bolomys lasiurus and 1 Rattus norvegicus) captured in an urban forest reserve in Campo Grande, State of Mato Grosso do Sul, Brazil. Of the ticks collected, 95 (78.9%) were in larval form and 22 (21.1%) were nymphs; the only adult (0.8%) was identified as A. cajennense. Viewed under dark-field microscopy in the fourth month after seeding, 9 cultures prepared from spleens and livers of the rodents, blood of the marsupials, and macerates of Amblyomma sp. nymphs revealed spiral-shaped, spirochete-like structures resembling those of Borrelia sp. Some of them showed little motility, while others were non-motile. No such structures could be found either in positive Giemsa-stained culture smears or under electron microscopy. No PCR amplification of DNA from those cultures could be obtained by employing Leptospira sp., B. burgdorferi, and Borrelia sp. primers. These aspects suggest that the spirochete-like structures found in this study do not fit into the genera Borrelia or Leptospira, requiring instead to be isolated for proper identification.