Asymptomatic lacrimal flow abnormalities in patients with septal deviations and turbinate hypertrophy

Background: This study aimed to investigate the lacrimal flow in patients affected by septal deviations and turbinate hypertrophy and to evaluate changes after rhinoseptoplasty with dacryocystography (DCT) and computed tomographic dacryocystography (CT-DCT). Methods: The study prospectively recruited patients having septal deviations with or without turbinate hypertrophy who underwent surgical evaluation for correction of their respiratory symptoms and were not referred for epiphora. Patients were excluded if they had undergone surgery for cranial vault defects or had experienced septal deviations after traumatic accidents. All patients were studied with DCT and CT-DCT preoperatively and postoperatively. Results: A total of 24 patients (10 men and 14 women) were recruited for the study. Of these patients, 11 (45.8%) had a reduced flow of the medium contrast due to a partial obstruction at the level of the internal ostium. All 11 patients had septal deviations and turbinate hypertrophy, whereas 8 patients had a unilateral obstruction (72.7%), and 3 patients had a bilateral obstruction (27.3%). All flows were corrected after surgery. Conclusions:The safe and well-tolerated radiologic techniques performed in this study provided detailed imaging of the lacrimal outflow system. A high incidence of partial obstruction to the internal ostium was found in patients with septal deviations, turbinate hypertrophy, and no lacrimal symptoms, suggesting a frequent presymptomatic condition

Age and gender specific normal values of left ventricular mass, volume and function for gradient echo magnetic resonance imaging: a cross sectional study

<p>Abstract</p> <p>Background</p> <p>Knowledge about age-specific normal values for left ventricular mass (LVM), end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and ejection fraction (EF) by cardiac magnetic resonance imaging (CMR) is of importance to differentiate between health and disease and to assess the severity of disease. The aims of the study were to determine age and gender specific normal reference values and to explore the normal physiological variation of these parameters from adolescence to late adulthood, in a cross sectional study.</p> <p>Methods</p> <p>Gradient echo CMR was performed at 1.5 T in 96 healthy volunteers (11–81 years, 50 male). Gender-specific analysis of parameters was undertaken in both absolute values and adjusted for body surface area (BSA).</p> <p>Results</p> <p>Age and gender specific normal ranges for LV volumes, mass and function are presented from the second through the eighth decade of life. LVM, ESV and EDV rose during adolescence and declined in adulthood. SV and EF decreased with age. Compared to adult females, adult males had higher BSA-adjusted values of EDV (p = 0.006) and ESV (p < 0.001), similar SV (p = 0.51) and lower EF (p = 0.014). No gender differences were seen in the youngest, 11–15 year, age range.</p> <p>Conclusion</p> <p>LV volumes, mass and function vary over a broad age range in healthy individuals. LV volumes and mass both rise in adolescence and decline with age. EF showed a rapid decline in adolescence compared to changes throughout adulthood. These findings demonstrate the need for age and gender specific normal ranges for clinical use.</p

Predictive factor for the response to adjuvant therapy with emphasis in breast cancer

One of the major challenges of early-stage breast cancer is to select the adjuvant therapy that ensures the most benefits and the least harm for the patient. The definition of accurate predictive factors is therefore of paramount importance. So far the choice of adjuvant therapy has been based on the number of affected lymph nodes and the hormone receptor status of the patient. This paper evaluates the use of other tumor-related markers as predictive factors for adjuvant therapy. These include HER2, p53 and Bcl-2, cathepsin B, p27, proliferating cell nuclear antigen (PCNA), cyclin D, Ki-67, and vascular endothelial growth factor (VEGF)

Reduced global longitudinal strain in association to increased left ventricular mass in patients with aortic valve stenosis and normal ejection fraction: a hybrid study combining echocardiography and magnetic resonance imaging

<p>Abstract</p> <p>Background</p> <p>Increased muscle mass index of the left ventricle (LVMi) is an independent predictor for the development of symptoms in patients with asymptomatic aortic stenosis (AS). While the onset of clinical symptoms and left ventricular systolic dysfunction determines a poor prognosis, the standard echocardiographic evaluation of LV dysfunction, only based on measurements of the LV ejection fraction (EF), may be insufficient for an early assessment of imminent heart failure. Contrary, 2-dimensional speckle tracking (2DS) seems to be superior in detecting subtle changes in myocardial function. The aim of the study was to assess these LV function deteriorations with global longitudinal strain (GLS) analysis and the relations to LVMi in patients with AS and normal EF.</p> <p>Methods</p> <p>50 patients with moderate to severe AS and 31 controls were enrolled. All patients underwent echocardiography, including 2DS imaging. LVMi measures were performed with magnetic resonance imaging in 38 patients with AS and indexed for body surface area.</p> <p>Results</p> <p>The total group of patients with AST showed a GLS of -15,2 ± 3,6% while the control group reached -19,5 ± 2,7% (p < 0,001). By splitting the group with AS in normal, moderate and severe increased LVMi, the GLS was -17,0 ± 2,6%, -13,2 ± 3,8% and -12,4 ± 2,9%, respectively (p = 0,001), where LVMi and GLS showed a significant correlation (r = 0,6, p < 0,001).</p> <p>Conclusions</p> <p>In conclusion, increased LVMi is reflected in abnormalities of GLS and the proportion of GLS impairment depends on the extent of LV hypertrophy. Therefore, simultaneous measurement of LVMi and GLS might be useful to identify patients at high risk for transition into heart failure who would benefit from aortic valve replacement irrespectively of LV EF.</p

Autoimmunity-Associated LYP-W620 Does Not Impair Thymic Negative Selection of Autoreactive T Cells.

A C1858T (R620W) variation in the PTPN22 gene encoding the tyrosine phosphatase LYP is a major risk factor for human autoimmunity. LYP is a known negative regulator of signaling through the T cell receptor (TCR), and murine Ptpn22 plays a role in thymic selection. However, the mechanism of action of the R620W variant in autoimmunity remains unclear. One model holds that LYP-W620 is a gain-of-function phosphatase that causes alterations in thymic negative selection and/or thymic output of regulatory T cells (Treg) through inhibition of thymic TCR signaling. To test this model, we generated mice in which the human LYP-W620 variant or its phosphatase-inactive mutant are expressed in developing thymocytes under control of the proximal Lck promoter. We found that LYP-W620 expression results in diminished thymocyte TCR signaling, thus modeling a "gain-of-function" of LYP at the signaling level. However, LYP-W620 transgenic mice display no alterations of thymic negative selection and no anomalies in thymic output of CD4(+)Foxp3(+) Treg were detected in these mice. Lck promoter-directed expression of the human transgene also causes no alteration in thymic repertoire or increase in disease severity in a model of rheumatoid arthritis, which depends on skewed thymic selection of CD4(+) T cells. Our data suggest that a gain-of-function of LYP is unlikely to increase risk of autoimmunity through alterations of thymic selection and that LYP likely acts in the periphery perhaps selectively in regulatory T cells or in another cell type to increase risk of autoimmunity

IL2RA/CD25 Gene Polymorphisms: Uneven Association with Multiple Sclerosis (MS) and Type 1 Diabetes (T1D)

[Background] IL-2 receptor (IL2R) alpha is the specific component of the high affinity IL2R system involved in the immune response and in the control of autoimmunity. [Methods and Results] Here we perform a replication and fine mapping of the IL2RA gene region analyzing 3 SNPs previously associated with multiple sclerosis (MS) and 5 SNPs associated with type 1 diabetes (T1D) in a collection of 798 MS patients and 927 matched Caucasian controls from the south of Spain. We observed association with MS in 6 of 8 SNPs. The rs1570538, at the 3′- UTR extreme of the gene, previously reported to have a weak association with MS, is replicated here (P = 0.032). The most associated T1D SNP (rs41295061) was not associated with MS in the present study. However, the rs35285258, belonging to another independent group of SNPs associated with T1D, showed the maximal association in this study but different risk allele. We replicated the association of only one (rs2104286) of the two IL2RA SNPs identified in the recently performed genome-wide association study of MS. [Conclusions] These findings confirm and extend the association of this gene with MS and reveal a genetic heterogeneity of the associated polymorphisms and risk alleles between MS and T1D suggesting different immunopathological roles of IL2RA in these two diseases.Financial support for the study was provided by the Ministerio de Educación y Ciencia (grants PN-SAF2006-02023 and TIN2007-67418-C03-03) and Junta de Andalucía (P07-CVI-02551) to A. Alcina and Servicio Andaluz de Salud de la Junta de Andalucía (grant PI0168/2007) to F. Matesanz. María Fedetz is a holder of a fellowship from Fundación IMABIS. Dorothy Ndagire is a holder of AECI-Ministerio de Asuntos Exteriores fellowship

Evaluation of ER, PgR, HER-2 and Ki-67 as predictors of response to neoadjuvant anthracycline chemotherapy for operable breast cancer

Primary systemic therapy (PST) for operable breast cancer enables the identification of in vivo biological markers that predict response to treatment. A total of 118 patients with T2–4 N0–1 M0 primary breast cancer received six cycles of anthracycline-based PST. Clinical and radiological response was assessed before and after treatment using UICC criteria. A grading system to score pathological response was devised. Diagnostic biopsies and postchemotherapy surgical specimens were stained for oestrogen (ER) and progesterone (PgR) receptor, HER-2 and cell proliferation (Ki-67). Clinical, radiological and pathological response rates were 78, 72 and 38%, respectively. There was a strong correlation between ER and PgR staining (P<0.0001). Higher Ki-67 proliferation indices were associated with PgR− tumours (median 28.3%, PgR+ 22.9%; P=0.042). There was no relationship between HER-2 and other biological markers. No single pretreatment or postchemotherapy biological parameter predicted response by any modality of assessment. In all, 10 tumours changed hormone receptor classification after chemotherapy (three ER, seven PgR); HER-2 staining changed in nine cases. Median Ki-67 index was 24.9% before and 18.1% after treatment (P=0.02); the median reduction in Ki-67 index after treatment was 21.2%. Tumours displaying >75% reduction in Ki-67 after chemotherapy were more likely to achieve a pathological response (77.8 vs 26.7%, P=0.004)

Proteins encoded in genomic regions associated with immune-mediated disease physically interact and suggest underlying biology

Genome-wide association studies have uncovered hundreds of DNA changes associated with complex disease. The ultimate promise of these studies is the understanding of disease biology; this goal, however, is not easily achieved because each disease has yielded numerous associations, each one pointing to a region of the genome, rather than a specific causal mutation. Presumably, the causal variants affect components of common molecular processes, and a first step in understanding the disease biology perturbed in patients is to identify connections among regions associated to disease. Since it has been reported in numerous Mendelian diseases that protein products of causal genes tend to physically bind each other, we chose to approach this problem using known protein–protein interactions to test whether any of the products of genes in five complex trait-associated loci bind each other. We applied several permutation methods and find robustly significant connectivity within four of the traits. In Crohn's disease and rheumatoid arthritis, we are able to show that these genes are co-expressed and that other proteins emerging in the network are enriched for association to disease. These findings suggest that, for the complex traits studied here, associated loci contain variants that affect common molecular processes, rather than distinct mechanisms specific to each association.Massachusetts Institute of Technology (MIT IDEA2 Program)Harvard University. Biological and Biomedical Sciences ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (NICHD RO1 grant HD055150-03)National Institute of Arthritis and Musculoskeletal and Skin Diseases (U.S.) (K08 NIH-NIAMS career development award (AR055688))National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (DK083756)National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (DK086502)Denmark. Forskningsradet for Sundhed og SygdomCenter for the Study of Inflammatory Bowel Diseas

Maternal Psychosocial Stress during Pregnancy and Placenta Weight: Evidence from a National Cohort Study

To study in a large-scale cohort with prospective data the associations between psychosocial stress during pregnancy and placenta weight at birth. Animal data suggest that the placenta is involved in stress-related fetal programming.; We defined a priori two types of psychosocial stress during pregnancy, life stress (perceived burdens in major areas of life) and emotional symptoms (e.g. anxiety). We estimated the associations of maternal stress during pregnancy with placenta weight at birth, controlled for length of gestation, by predicting gestational age- and sex-specific z-scores of placenta weight through multiple regression analysis, adjusted for potential confounders (N?=?78,017 singleton pregnancies). Life stress (per increase in stress score by 1, range: 0-18) during pregnancy was associated with increased placenta weight at birth (z-score, reported in 10(-3); B, 14.33; CI, 10.12-18.54). In contrast, emotional symptoms during pregnancy were not associated with placenta weight at birth.; Maternal life stress but not emotional symptoms during pregnancy was associated with increased placenta weight at birth; yet, the association-estimate was rather small. Our results may contribute to a better understanding of the role of the placenta in the regulation of intrauterine processes in response to maternal stress