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- Aksentijevich, Ivona, et al.
(författare)
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An Autoinflammatory Disease with Deficiency of the Interleukin-1-Receptor Antagonist
- 2009
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 360:23, s. 2426-2437
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Autoinflammatory diseases manifest inflammation without evidence of infection, high-titer autoantibodies, or autoreactive T cells. We report a disorder caused by mutations of IL1RN, which encodes the interleukin-1-receptor antagonist, with prominent involvement of skin and bone. METHODS We studied nine children from six families who had neonatal onset of sterile multifocal osteomyelitis, periostitis, and pustulosis. Response to empirical treatment with the recombinant interleukin-1-receptor antagonist anakinra in the first patient prompted us to test for the presence of mutations and changes in proteins and their function in interleukin-1-pathway genes including IL1RN. RESULTS We identified homozygous mutations of IL1RN in nine affected children, from one family from Newfoundland, Canada, three families from the Netherlands, and one consanguineous family from Lebanon. A nonconsanguineous patient from Puerto Rico was homozygous for a genomic deletion that includes IL1RN and five other interleukin-1-family members. At least three of the mutations are founder mutations; heterozygous carriers were asymptomatic, with no cytokine abnormalities in vitro. The IL1RN mutations resulted in a truncated protein that is not secreted, thereby rendering cells hyperresponsive to interleukin-1 beta stimulation. Patients treated with anakinra responded rapidly. CONCLUSIONS We propose the term deficiency of the interleukin-1-receptor antagonist, or DIRA, to denote this autosomal recessive autoinflammatory disease caused by mutations affecting IL1RN. The absence of interleukin-1-receptor antagonist allows unopposed action of interleukin-1, resulting in life-threatening systemic inflammation with skin and bone involvement. (ClinicalTrials.gov number, NCT00059748.)
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| 2. |
- Ovhed, I, et al.
(författare)
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What is the future of primary care research? Probably fairly bright, if we may believe the historical development
- 2005
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Ingår i: Scandinavian Journal of Primary Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 23:4, s. 248-253
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To study one aspect of the development of primary care research from 1975 to 2003. Design. Quantitative bibliometric study. Setting. Pub Med database. Subjects. Four Nordic countries (Denmark, Finland, Norway, and Sweden), seven countries from the rest of Europe (Belgium, France, Germany, Italy, the Netherlands, Spain, and the UK), and seven countries from the rest of the world (Australia, Canada, India, Japan, New Zealand, South Africa, and the USA). Main outcome measures. Number of primary healthcare publications per million inhabitants. Percentage of publications in primary healthcare of all publications in human medicine. Results. In 2003, New Zealand, the UK, and Australia were in the lead, with barely 20 primary care publications per million inhabitants, followed by Norway, Sweden, the Netherlands, and Denmark, where the corresponding figure was around 10. A vigorous increase in publications from 1975 to 2003 was clearly seen in most of the countries. However, during the same period the proportion of publications from primary care in relation to all publications in human medicine was only moderately increased, or virtually unchanged. Conclusion. It is believed that primary care research has a future, and it is hoped it may even be bright. However, searching Pub Med gave but one aspect of the historical development, and in particular the comparisons between countries may be questionable.
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