Role of cytokines and chemokines in prion infections of the central nervous system

Prion infections of the central nervous system (CNS) are characterised by a reactive gliosis and the subsequent degeneration of neuronal tissue. The activation of glial cells, which precedes neuronal death, is likely to be initially caused by the deposition of misfolded, proteinase K-resistant, isoforms (termed PrP(res)) of the prion protein (PrP) in the brain. Cytokines and chemokines released by PrP(res)-activated glia cells may contribute directly or indirectly to the disease development by enhancement and generalisation of the gliosis and via cytotoxicity for neurons. However, the actual role of prion-induced glia activation and subsequent cytokine/chemokine secretion in disease development is still far from clear. In the present work, we review our present knowledge concerning the functional biology of cytokines and chemokines in prion infections of the CNS.     

What methods do stakeholders prefer for feeding back performance data: a qualitative study in palliative care.

OBJECTIVE: To investigate the opinions of stakeholders (service commissioners and providers) on how performance data should be presented, in order to develop effective feedback methods to facilitate the use of these data in decision making. DESIGN: A qualitative analysis of semi-structured face-to-face and telephone interviews. League tables and fictional box plots were presented as an illustrative guide. The themes covered in the interviews were the effectiveness of these two feedback formats, their positive and negative characteristics, and ideas for new and improved feedback mechanisms. PARTICIPANTS: Thirty-six stakeholders representing a range of clinical and non-clinical roles within palliative care and the wider health care system across a variety of statutory and non-statutory organizations from London and the West Midlands. RESULTS: Box plots were received more positively than league tables, and qualitative information was considered more appropriate than pictorial feedback. Conventional methods such as league tables and box plots were judged to lack essential information on which important decisions could be based, such as additional contextual information and the methodological assumptions of the instrument. Both feedback methods were considered useful as an impetus to further discussion. There was a consensus that feedback should be constructive and able to be adapted to the organizational realities in which UK health services function. CONCLUSION: Qualitative research was viewed as the right evidence for gaining an understanding of the quality of end of life care. Stakeholders highlighted the importance of the lay perspective, which requires approaches that illuminate the subjective meanings of patient experience.     

Biliary excretion of radioactivity after intravenous administration of [3H]25-hydroxyvitamin D3 in man

The biliary excretion of radioactivity after intravenous [3H]25-hydroxyvitamin D3 was studied in nine patients with T-tube bile drainage. The mean +/- SD 24-hr radioactivity excretion in T-tube bile expressed as a percentage of the administered dose was 6.7 +/- 2.9%; after correction for incomplete bile collection, the value obtained was 16.0 +/- 11.1%. Chloroform solubility of biliary radioactivity increased from 27.4 +/- 8.9% to 72.9 +/- 10.1% following incubation with beta-glucuronidase. High-performance liquid chromatographic analysis of chloroform extracts of bile revealed that most of the eluted radioactivity was more polar than [3H]25-hydroxyvitamin D3. No free [3H]25-hydroxyvitamin D3 was demonstrated. Thus in man, most of the biliary radioactivity excreted following [3H]25-hydroxyvitamin D3 is in the form of water-soluble compounds, mainly glucuronides. However, our results suggest that glucuronides of metabolites other than 25-OHD3 are predominantly formed.     

Risk factors for neck pain in office workers: a prospective study

Background  

Persisting neck pain is common in society. It has been reported that the prevalence of neck pain in office workers is much higher than in the general population. The costs to the worker, employer and society associated with work-related neck pain are known to be considerable and are escalating. The factors that place office workers at greater risk of developing neck pain are not understood. The aim of this study is to investigate the incidence and risk factors of work-related neck pain in Australian office workers.     

Exhaled nitric oxide in healthy children: Variability and a lack of correlation with atopy

Nitric oxide (NO) is a free radical produced by several lung cells via the enzyme nitric oxide synthetase (NOS) and can be easily measured in exhaled air by chemiluminescence analysis. As the iso-enzyme iNOS may be induced by cytokines and endotoxin, NO is elevated in several chronic inflammatory airway diseases. Prior to using exhaled nitric oxide (eNO) as a non-invasive marker of airway inflammation in daily routine, the role of possibly influencing factors such as age, time of the day, smoking exposure and intra-individual variability have to be clarified. NO concentrations were measured in 107 healthy children aged 4–18 years at an expiratory flow of 184 ml/s. Spirometry and a skin-prick test were performed and a questionnaire on family history of atopy, personal symptoms of atopic disease and smoke exposure was completed. For intra-individual variability nitric oxide was measured in six children three times daily on 6 consecutive days. Median eNO concentration was 5.7 p.p.b., and increased significantly with age but did not vary with gender. No correlation was found between eNO and smoke exposure, positive skin-prick test, FEV ₁, MEF₂₅ and time of the day. There was no circadian rhythm found in the six children measured on 6 consecutive days, but the eNO showed an intra-individual coefficient of variation of 25.9%. With the help of a two-compartment model of the lung the alveolar NO concentration was estimated to be 4.1 p.p.b and was shown to be constant with age, whereas the airway part of NO steadily increased with age. When comparing eNO values with standardized measurement techniques, the age of the children and the large intra-subject coefficient of variation have to be taken into account, whereas in healthy children subject-specific factors such as atopic history, gender and skin test reactivity did not affect eNO measurement.