Structures of the lamin A/C R335W and E347K mutants: implications for dilated cardiolaminopathies

Dilated cardiomyopathy (DCM) is a condition whereby the normal muscular function of the myocardium is altered by specific or multiple aetiologies. About 25-35% of DCM patients show familial forms of the disease, with most mutations affecting genes encoding cytoskeletal proteins. Most of the DCM-related mutations fall in the Lamin AC gene, in particular in the Coil2B domain of the encoded protein. In this context, we focussed our studies on the crystal structures of two lamin Coil2B domain mutants (R335W and E347K). Both R335 and E347 are higly conserved residues whose substitution has little effects on the Coil2B domain three-dimensional structure; we can thus hypothesize that the mutations may interfere with the binding of components within the nuclear lamina, or of nuclear factors, that have been proposed to interact/associate with lamin A/C

Long term efficacy of insulin pump therapy in preschool children with diabetes

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Autosomal Recessive Atrial Dilated Cardiomyopathy With Standstill Evolution Associated With Mutation of Natriuretic Peptide Precursor A

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FRI0215 Comparative efficacy and retention rate of tocilizumab and tnf inhibitors used in combination with methotrexate as first-line biologic therapy in rheumatoid arthritis: data from a multicentre observational registry

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Necrobiosis lipoidica diabeticorum : A pediatric case report

Introduction: Necrobiosis lipoidica (NL) is a rare chronic granulomatous dermatitis that usually appears in the lower extremities. It affects about 0.3-1.2% of diabetic patients, the majority of whom have type 1 diabetes. The etiology and pathogenesis of this disorder are still unclear. NL is characterized by skin rash that usually affects the shins. The average onset is 30 years, with females being affected more commonly. There are very few reported cases of necrobiosis lipoidica in children. Case report: We report a case of a 16 year old girl affected by type 1 diabetes mellitus (15 years disease duration) who developed an erythematous nodular rash on the lower extremities and interscapular area. In the suspect of necrobiosis lipoidica, a skin biopsy was performed (lower extremities and interscapular area). The microscopic evaluation of the pretibial lesions was suggestive of necrobiosis lipoidica. The smaller lesions in the interscapular area showed signs of perivascular dermatitis which could be consistent with early stages of necrobiosis lipoidica. Local treatment with tacrolimus determined a progressive improvement of the lesions. Conclusion: In patients with T1DM, diagnosis of NL of the lower legs is usually unequivocal. However, diagnosis may be more challenging in the presence of lesions with recent onset and/or atypical clinical presentation and unusual site. In these cases, NL must always be taken in consideration in order to avoid misdiagnosis, wrong/late treatment decisions and progression to ulceration

Doxorubicin versus doxorubicin and cisplatin in endometrial carcinoma: definitive results of a randomised study (55872) by the EORTC Gynaecological Cancer Group

Background: Combination chemotherapy yields better response rates which do not always lead to a survival advantage. The aim of this study was to investigate whether the reported differences in the efficacy and toxicity of monotherapy with doxorubicin (DOX) versus combination therapy with cisplatin (CDDP) in endometrial adenocarcinoma lead to significant advantage in favour of the combination. Patients and methods: Eligible patients had histologically-proven advanced and/or recurrent endometrial adenocarcinoma and were chemo-naïve. Treatment consisted of either DOX 60 mg/m2 alone or CDDP 50 mg/m2 added to DOX 60 mg/m2, every 4 weeks. Results: A total of 177 patients were entered and median follow-up is 7.1 years. The combination DOX-CDDP was more toxic than DOX alone. Haematological toxicity consisted mainly of white blood cell toxicity grade 3 and 4 (55% versus 30%). Non-haematological toxicity consisted mainly of grade 3 and 4 alopecia (72% versus 65%) and nausea/vomiting (36 % versus 12%). The combination DOX-CDDP provided a significantly higher response rate than single agent DOX (P <0.001). Thirty-nine patients (43%) responded on DOX-CDDP [13 complete responses (CRs) and 26 partial responses (PRs)], versus 15 patients (17%) on DOX alone (8 CR and 7 PR). The median overall survival (OS) was 9 months in the DOX-CDDP arm versus 7 months in the DOX alone arm (Wilcoxon P = 0.0654). Regression analysis showed that WHO performance status was statistically significant as a prognostic factor for survival, and stratifying for this factor, treatment effect reaches significance (hazard ratio = 1.46, 95% confidence interval 1.05-2.03, P = 0.024). Conclusions: In comparison to single agent DOX, the combination of DOX-CDDP results in higher but acceptable toxicity. The response rate produced is significantly higher, and a modest survival benefit is achieved with this combination regimen, especially in patients with a good performance statu

The need to modify patient selection to improve the benefits of implantable cardioverter-defibrillator for primary prevention of sudden death in non-ischaemic dilated cardiomyopathy

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