The Promher Study: An Observational Italian Study on Adjuvant Therapy for HER2-Positive, pT1a-b pN0 Breast Cancer.

Background: The management of pT1a-b pN0 HER2-positive breast cancer is controversial and no data about the efficacy of trastuzumab in this setting are available from randomized clinical trials. The aims of this retrospective study were to assess how patients are managed in clinical practice in Italy, which clinical or biological characteristics influenced the choice of adjuvant systemic therapy and the outcome of patients.

Methods: Data of consecutive patients who underwent surgery from January 2007 to December 2012 for HER2-positive, pT1a-b pN0 M0 breast cancer were retrospectively collected from 28 Italian centres.

Dural ectasia and FBN1 mutation screening of 40 patients with Marfan syndrome and related disorders: role of dural ectasia for the diagnosis.

Marfan syndrome is an autosomal dominant disorder of connective tissue caused by mutations in the gene encoding fibrillin-1 (FBN1), a matrix component of microfibrils. Dural ectasia, i.e.

Fibroblast autofluorescence in connective tissue disorders: a future tool for clinical and differential diagnosis?

Marfan syndrome (MFS) is an inherited disorder of connective tissue due to mutations in FBN1 (90%) and TGFBR1 and TGFBR2 (5 to 10%) genes. Clinical and differential diagnosis is difficult because of the inter- and intrafamiliar marked heterogeneity and the variable onset age of clinical manifestations. Among the disorders, in differential diagnosis, thoracic aortic aneurysm (TAA) and Ullrich scleroatonic muscular dystrophy (UCMD) are reported.

Vascular and connective tissue features in 5 Italian patients with homocystinuria.

Homocystinuria is a metabolic disorder associated with defects in genes encoding for methionine metabolism enzymes. Vascular and connective tissue manifestations such as deep venous thrombosis, ectopia lentis and skeletal alterations are the major clinical features. We investigated the clinical manifestations of 5 Italian homocystinuric patients, performed mutation screening analysis on cystationine beta-synthase (CBS) gene and searched for genotype/phenotype correlations.

Is ectopia lentis in some cases a mild phenotypic expression of Marfan syndrome? Need for a long-term follow-up.

Purpose: Ectopia lentis (EL) and Marfan syndrome (MFS) are considered two distinct clinical entities. We performed genetic and clinical studies to investigate whether EL is actually distinct from MFS or if it is a mild phenotypic expression of it.

Methods: Seven patients with EL were followed for 5-10 years.

May TGFBR1 act also as low penetrance allele in Marfan syndrome?

Marfan syndrome, a human disease involving cardiovascular and skeletal apparatuses and ocular and central nervous systems, is associated to mutations in FBN1 gene; heterozygous mutations in TGFBR2 and TGFBR1 genes were found associated to MFS type 2, characterized by the presence of skeletal and cardiovascular major criteria and absence of eye major criterion. We screened the TGFBR1 gene in 46 Marfan patients in whom mutations in FBN1 and TGFBR2 genes were excluded and the analysis of Ex1 was extended to additional 114 Marfan patients and 237 controls. We detected two potentially pathological sequence variants: the TGFBR1 6Ala allele whose frequency was higher in the group of Marfan patients (0.

Zinc finger protein Zac1 is expressed in chondrogenic sites of the mouse.

Zac1 is a zinc finger transcription factor that elicits antiproliferative activity and is a potential tumor suppressor gene. Through a detailed spatiotemporal study by in situ hybridization of mouse embryos, we have found that Zac1 transcript is predominantly localized in developing chondrogenic tissue, in addition to the central nervous system as reported elsewhere. Zac1 is also expressed transiently in the myocardium, skeletal muscle, and basal aspect of the stratified embryonic epithelia.

Phenotypic variability of cardiovascular manifestations in Marfan Syndrome. Possible role of hyperhomocysteinemia and C677T MTHFR gene polymorphism.

Aims: The aim of this study was to evaluate (1) homocysteinemia and the prevalence of the C677T MTHFR polymorphism in Marfan patients and (2) whether the severity of cardiovascular manifestations is associated with homocysteinemia and/or C677T polymorphism.

Methods And Results: We studied 107 patients subdivided into three subgroups based on the severity of cardiovascular manifestations: (A) no involvement (n=4); (B) mild involvement (n=45); (C) aortic dilatation or aortic dissection (n=58), and 189 controls. Total homocysteine (tHcy) was significantly higher in subgroup C than in subgroup B.

Post-ischemic myocardial fibrosis occurs independent of hemodynamic changes.

Objectives: Myocardial fibrosis is a major component of ventricular remodeling after large myocardial infarction (MI). The present study tests the hypothesis that post-ischemic myocardial fibrosis can occur independent of hemodynamic changes.

Methods: A mouse model of distal left coronary artery ligation was established to induce a small infarct (less than 15% of the left ventricle) in order to avoid significant mechanical overload after permanent myocardial ischemia.

Genetic determinants of fasting and post-methionine hyperhomocysteinemia in patients with retinal vein occlusion.

Introduction: Moderate hyperhomocysteinemia is considered a risk factor for both venous and arterial thrombosis. A prevalence of up to 30% of fasting hyperhomocysteinemia has been recently reported in patients with retinal vein occlusion (RVO) whereas conflicting data exist on the role of C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene as a risk factor for RVO. No report has been published on cystathionine beta-synthase (CBS) 844ins68 polymorphism (another genetic determinant of blood Hcy levels) in RVO patients.

Evaluation of a new point-of-care celite-activated clotting time analyzer in different clinical settings. The i-STAT celite-activated clotting time test.

Background: Activated clotting time (ACT) is used to monitor heparin therapy during cardiopulmonary bypass, interventional cardiology, and hemodialysis. Traditionally, ACT is performed by use of the Hemochron system. Recently, a new device, the i-STAT system, has been introduced to measure ACT.

Prominent expression of lysyl oxidase during mouse embryonic cardiovascular development.

By mRNA differential display in mouse hearts, lysyl oxidase (Lox), a key enzyme catalyzing cross-links in elastin and collagens, was found to be up-regulated between embryonic days 11 (E11) and 13 (E13). This was confirmed by semiquantitative RT-PCR. We analyzed its spatio-temporal expression pattern by in situ hybridization in regard to the development of myocardial cells, endocardial cushion tissue, aortic arch vessels, and epicardium.