Making Chronic Conditions Count: 4. Stroke

Chronic conditions are responsible for a significant proportion of early deaths. They reduce quality of life in many of the adults living with them, represent substantial financial costs to patients and the health and social care system, and cause a significant loss of productivity to the economy. This report contains estimates and forecasts of the population prevalence of stroke, and it shows how it varies across the island and what change is expected between 2007, 2015 and 2020.

Effects of the 45;₂-adrenergic agonist clonidine on the pharmacodynamics and pharmacokinetics of 3,4-methylenedioxymethamphetamine in healthy volunteers.

The mechanism of action of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) involves the carrier-mediated and potentially vesicular release of monoamines. We assessed the effects of the sympatholytic 45;₂-adrenergic receptor agonist clonidine (150 μg p.o.), which inhibits the neuronal vesicular release of norepinephrine, on the cardiovascular and psychotropic response to MDMA (125 mg p.o.) in 16 healthy subjects. The study used a randomized, double-blind, placebo-controlled crossover design with four experimental sessions. The administration of clonidine 1 h before MDMA reduced the MDMA-induced increases in plasma norepinephrine concentrations and blood pressure but only to the extent that clonidine lowered norepinephrine levels and blood pressure compared with placebo. Thus, no interaction was found between the cardiovascular effects of the two drugs. Clonidine did not affect the psychotropic effects or pharmacokinetics of MDMA. The lack of an interaction of the effects of clonidine and MDMA indicates that vesicular release of norepinephrine, which is inhibited by clonidine, does not critically contribute to the effects of MDMA in humans. Although clonidine may be used in the treatment of stimulant-induced hypertensive reactions, the present findings do not support a role for 45;₂-adrenergic receptor agonists in the prevention of psychostimulant dependence.

The use of the murine model of infection with Leishmania major to reveal the antagonistic effects that IL-4 can exert on T helper cell development and demonstrate that these opposite effects depend upon the nature of the cells targeted for IL-4 signaling.

In contrast to mice from the majority of inbred strains, BALB mice develop aberrant Th2 responses and suffer progressive disease after infection with Leishmania major. These outcomes depend on the production of Interleukin 4, during the first 2 d of infection, by CD4+ T cells that express the Vbeta4-Valpha8 T cell receptors specific for a dominant I-A(d) restricted epitope of the LACK antigen from L. major. In contrast to this well established role of IL-4 in Th2 cell maturation, we have recently shown that, when limited to the initial period of activation of dendritic cells by L. major preceding T cell priming, IL-4 directs DCs to produce IL-12, promotes Th1 cell maturation and resistance to L. major in otherwise susceptible BALB/c mice. Thus, the antagonistic effects that IL-4 can have on Th cell development depend upon the nature of the cells (DCs or primed T cells) targeted for IL-4 signaling.

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

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

RATIONALE: AICAR (5-aminoimidazole-4-carboxamide 1 46;-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.