Adult-Onset Still's disease (AOSD) is a rare condition of unknown origin with various presentations and unpredictable outcome. The aim of this study was to analyse clinical and biological ...presentation, and outcome of patients admitted to an internal medicine service.
A retrospective cohort design with prospective follow-up was used. All the patients admitted to our internal medicine service for AOSD between January 1998 and March 2004 were included.
According to Yamaguchi's classification criteria, 17 patients were analysed with a mean age at onset of 37.3 years and a 2.4 sex-ratio (female/male). Mean follow-up length was 52.1 months. Eight patients developed a monocyclic systemic form, 8 a polycyclic systemic form and 1 a chronic articular form. Arthralgia (87%) and arthritis (53%) were less frequent than in other series. Sixteen patients were treated: 14 by corticosteroids, 6 by non-steroid anti-inflammatory drugs, 5 by methotrexate, 2 intravenous polyglobulin and one by anti-TNF drug. Patients with a corticodependant or corticoresistant form had more polyarthritis at the onset of the disease (3/6 vs 0/11, P=0.029).
In internal medicine activity, AOSD without oligo- or polyarthritis may be more frequent than expected according to the literature. Corticotherapy alone is often efficient in these AOSD form without synovitis, and methotrexate use is uncommon.
La maladie de Still de l'adulte (MSA) est une affection rare de présentation et d'évolution très variables. L'objectif est d'étudier les caractéristiques cliniques, biologiques et évolutives des ...patients atteints de MSA pris en charge en médecine interne.
Étude rétrospective des patients suivis dans un service de médecine interne du 1
er janvier 1998 au 31 mars 2004, avec actualisation en avril 2004 des données évolutives.
Dix-sept patients répondant aux critères de Yamaguchi ont été inclus. Leur âge moyen au début était de 37,3 ans, le sex-ratio (femme/homme) de 2,4, et la durée moyenne de suivi de 52,1 mois. Huit patients ont évolué sur un mode monocyclique systémique, huit sur un mode polycyclique systémique et un sur un mode articulaire chronique. Les arthralgies (82 %) et le gonflement articulaire (53 %) étaient plus rares que dans les autres séries de la littérature. Seize patients ont reçu un traitement médicamenteux : 14 une corticothérapie, six des anti-inflammatoires non stéroïdiens, cinq du méthotrexate, deux des immunoglobulines intraveineuses et un, un anticorps anti-TNF. Les patients ayant évolué vers une dépendance ou résistance aux corticoïdes avaient, initialement plus de polyarthrites (trois malades sur six contre 0 sur 11,
p
=
0,029).
Dans un service de médecine interne, les maladies de Still de l'adulte sans oligo- ou polyarthrite pourraient être plus fréquentes que ne le laisse supposer l'analyse de la littérature. Dans ces formes non fluxionnaires une corticothérapie exclusive suffit le plus souvent à maîtriser la maladie, et le recours au méthotrexate est rarement nécessaire.
Adult-Onset Still's disease (AOSD) is a rare condition of unknown origin with various presentations and unpredictable outcome. The aim of this study was to analyse clinical and biological presentation, and outcome of patients admitted to an internal medicine service.
A retrospective cohort design with prospective follow-up was used. All the patients admitted to our internal medicine service for AOSD between January 1998 and March 2004 were included.
According to Yamaguchi's classification criteria, 17 patients were analysed with a mean age at onset of 37.3 years and a 2.4 sex-ratio (female/male). Mean follow-up length was 52.1 months. Eight patients developed a monocyclic systemic form, 8 a polycyclic systemic form and 1 a chronic articular form. Arthralgia (87%) and arthritis (53%) were less frequent than in other series. Sixteen patients were treated: 14 by corticosteroids, 6 by non-steroid anti-inflammatory drugs, 5 by methotrexate, 2 intravenous polyglobulin and one by anti-TNF drug. Patients with a corticodependant or corticoresistant form had more polyarthritis at the onset of the disease (3/6 vs 0/11,
P
=
0.029).
In internal medicine activity, AOSD without oligo- or polyarthritis may be more frequent than expected according to the literature. Corticotherapy alone is often efficient in these AOSD form without synovitis, and methotrexate use is uncommon.
Cyclooxygenase (COX)-2 and COX-1 play an important role in prostacyclin production in vessels and participate in maintaining vascular homeostasis. Statins are inhibitors of 3-hydroxy-3-methylglutaryl ...coenzyme A (HMG CoA) reductase, which is crucial in cholesterol biosynthesis. Recently, cholesterol-independent effects of statins have been described. In this study, we evaluated the effect of two inhibitors of HMG CoA reductase, mevastatin and lovastatin, on the production of prostacyclin and the expression of COX in human aortic smooth muscle cells. Treatment of cells with 25 microm mevastatin or lovastatin resulted in the induction of COX-2 and increase in prostacyclin production. Mevalonate, the direct metabolite of HMG CoA reductase, and geranylgeranyl-pyrophosphate reversed this effect. GGTI-286, a selective inhibitor of geranylgeranyltransferases, increased COX-2 expression and prostacyclin formation, thus indicating the involvement of geranylgeranylated proteins in the down-regulation of COX-2. Furthermore, Clostridium difficile toxin B, an inhibitor of the Rho GTP-binding protein family, the Rho selective inhibitor C3 transferase, and Y-27632, a selective inhibitor of the Rho-associated kinases, targets of Rho A, increased COX-2 expression whereas the activator of the Rho GTPase, the cytotoxic necrotizing factor 1, blocked interlukin-1alpha-dependent COX-2 induction. These results demonstrate that statins up-regulate COX-2 expression and subsequent prostacyclin formation in human aortic smooth muscle cells in part through inhibition of Rho.
STAT transcription factors are induced by a number of growth factors and cytokines. Within minutes of induction, the STAT proteins are phosphorylated on tyrosine and serine residues and translocated ...to the nucleus, where they bind to their DNA targets. The leukemia inhibitory factor (LIF) mediates pleiotropic and sometimes opposite effects both in vivo and in cultured cells. It is known, for example, to prevent differentiation of embryonic stem (ES) cells in vitro. To get insights into LIF-regulated signaling in ES cells, we have analyzed protein-binding and transcriptional properties of STAT recognition sites in ES cells cultivated in the presence and in the absence of LIF. We have detected a specific LIF-regulated DNA-binding activity implicating the STAT3 protein. We show that STAT3 phosphorylation is essential for this LIF-dependent DNA-binding activity. The possibility that ERK2 or a closely related protein kinase, whose activity is modulated in a LIF-dependent manner, contributes to this phosphorylation is discussed. Finally, we show that the multimerized STAT3-binding DNA element confers LIF responsiveness to a minimal thymidine kinase promoter. This, together with our observation that overexpression of STAT3 dominant-negative mutants abrogates this LIF responsiveness, clearly indicates that STAT3 is involved in LIF-regulated transcriptional events in ES cells. Finally, stable expression of such a dominant negative mutant of STAT3 induces morphological differentiation of ES cells despite continuous LIF supply. Our results suggest that STAT3 is a critical target of the LIF signaling pathway, which maintains pluripotent cell proliferation.
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