Multigenic control of skin tumor susceptibility in SENCARA/Pt mice

Skin tumors induced in mice by initiation-promotion (2 microg DMBA-2 microg TPA) protocols were found to be under multigenic control. Eighty- one N2 mice from the cross (BALB/cAnPt x SENCARA/Pt)F1 x SENCARA/Pt that were either solidly resistant (no papillomas) or highly susceptible (> or = 7 papillomas/mouse) were subjected to a 'genome scan' using 89 microsatellite markers to check for associations with susceptible and resistant phenotypes. A locus on Chr 5 (Skts4) was found to control the susceptibility of SENCARA/Pt mice and the resistance of BALB/cAnPt mice to papilloma formation. In addition, higher than expected linkage scores were seen for the markers D9Mit271, D11Mit268 and D12Mit56. Further work is required to establish whether genes determining papilloma formation are located in these regions of the genome. In general, no evidence was seen for loss of heterozygosity in microsatellite markers on Chrs 5, 9 and 11 in 17 microdissected papillomas from (BALB/c x SENCARA)F1 hybrid mice.      

Evidence-based recommendations for the management of ankylosing spondylitis: systematic literature search of the 3E Initiative in Rheumatology involving a broad panel of experts and practising rheumatologists

Objective. Recommendations and/or guidelines represent a popularway of integrating evidence-based medicine into clinical practice.The 3E Initiatives is a multi-national effort to develop recommendationsfor the management of rheumatic diseases, which involves a largenumber of experts combined with practising rheumatologists addressingspecific questions relevant to clinical practice. Methods. Ten countries participated in three rounds of discussionsand votes concerning the management of AS. A set of nine questionswas formulated in the domains of diagnosis, monitoring and treatment,after a Delphi procedure. A literature search in MedLine wasconducted. Predefined outcome parameters for the domains ofdiagnosis, monitoring and treatment were assessed. The evidenceto support each proposition was evaluated and scored. Afterdiscussion and votes, the final recommendations were presentedusing brief statements by each national group, following whichthe final international recommendations were formulated. Results. A total of 2699 papers were found and 467 were selectedfor analysis. Twelve key recommendations were developed: threein the domain of diagnosis addressing general diagnostic considerations,early AS diagnosis and general practitioners’ referralrecommendations; three concerning monitoring of AS disease activity,severity and prognosis; six concerning pharmacological treatment(except biologics): non-steroidal anti-inflammatory drugs/COX-IIinhibitors, bisphosphonates and treatment of enthesitis. Thecompiled agreement among experts ranged from 72% to 93%. Conclusion. Recommendations for the management of AS were developedusing an evidence-based approach followed by expert/physicianconsensus with high level of agreement. Involvement of a largerand more representative group of rheumatologists may improvetheir dissemination and implementation in daily clinical practice. KEY WORDS: Ankylosing spondylitis, Systemic literature search, Recommendations, Non-steroidal anti-inflammatory drugs, COX-II inhibitors, Monitoring, Diagnosis, Treatment     

Recent progress in the treatment of lupus nephritis

The treatment of lupus nephritis has seen significant advances during the past decade mainly due to the publication of well-designed randomized clinical trials (RCTs). The choice of treatment is guided by the histopathologic classification but is also influenced by demographic, clinical, and laboratory characteristics that allow for the identification of patients at risk for more aggressive disease. For the induction arm, low-dose cyclophosphamide regimens and mycophenolate mofetil have been validated as alternatives to the established National Institutes of Health regimen of high-dose cyclophosphamide; for the maintenance phase, azathioprine and mycophenolate compete for treatment of first choice. Rituximab is efficacious in real-life clinical practice but ineffective in clinical trials. The role of recently approved belimumab in lupus nephritis eagerly awaits further documentation. Aggressive management of comorbid conditions, such as hypertension and dyslipidemia, is of utmost importance. Here, we review the latest advances in lupus nephritis therapy with a focus on recent RCTs as well as new biologic agents under development. Furthermore, we propose a therapeutic algorithm in an effort to facilitate clinical decision-making in this gradually changing landscape. Upcoming European and American recommendations should provide further clarification.     

Pulse cyclophosphamide for severe neuropsychiatric lupus.

We studied the effect of parenteral pulse cyclophosphamide therapy in nine patients with active systemic lupus erythematosus and severe central nervous system involvement. Seven patients had focal neurological deficits and/or seizures associated with abnormalities on cerebrospinal fluid analysis and/or magnetic resonance imaging. Two patients had organic brain syndrome with psychosis and normal cerebrospinal fluid and/or magnetic resonance imaging analysis. Six patients were unresponsive to treatment with high dose corticosteroid. Cyclophosphamide, 0.75-1.0 g/m2 body surface area, was administered intravenously every month for at least 2 months. Eight patients had a complete recovery or recovered with minor residuals. Cyclophosphamide was well tolerated with few side effects. We conclude that parenteral pulse cyclophosphamide is an effective adjunctive therapy for the management of patients with active systemic lupus erythematosus and central nervous system symptoms.