Topoisomerase II alpha amplification may predict benefit from adjuvant anthracyclines in HER2 positive early breast cancer

The purpose of the study was to evaluate the use of metabolic phenotype, described by high-resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS), as a tool for prediction of histological grade, hormone status, and axillary lymphatic spread in breast cancer patients. Biopsies from breast cancer (n = 91) and adjacent non-involved tissue (n = 48) were excised from patients (n = 77) during surgery. HR MAS MR spectra of intact samples were acquired. Multivariate models relating spectral data to histological grade, lymphatic spread, and hormone status were designed. The multivariate methods applied were variable reduction by principal component analysis (PCA) or partial least-squares regression-uninformative variable elimination (PLS-UVE), and modelling by PLS, probabilistic neural network (PNN), or cascade correlation neural network. In the end, model verification by prediction of blind samples (n = 12) was performed. Validation of PNN training resulted in sensitivity and specificity ranging from 83 to 100% for all predictions. Verification of models by blind sample testing showed that hormone status was well predicted by both PNN and PLS (11 of 12 correct), lymphatic spread was best predicted by PLS (8 of 12), whereas PLS-UVE PNN was the best approach for predicting grade (9 of 12 correct). MR-determined metabolic phenotype may have a future role as a supplement for clinical decision-making-concerning adjuvant treatment and the adaptation to more individualised treatment protocols.     

Postprandial glucose, insulin and gastrointestinal hormones in healthy and diabetic subjects fed a fructose-free and resistant starch type IV-enriched enteral formula

Background

Reducing the dietary glycaemic response has been proposed as a means of reducing the risk of diabetes.

Aim

To evaluate the effects of a new diabetes-specific formula (DSF) enriched with resistant starch type IV and fructose-free on postprandial glycaemia, insulinaemia and gastrointestinal hormones in healthy volunteers and in outpatient type 2 diabetics.

Methods

(1) Twenty-four healthy volunteers were divided into two groups: Group 1 ( n = 10) was provided 50 g of the carbohydrate (CHO) constituent of the new product and 50 g of glucose separated by 1 week; Group 2 ( n = 14) was provided 400 ml of the new DSF (T-Diet Plus^® Diabet NP) and 400 ml of a control product separated by 1 week. (2) Ten type 2 diabetic patients received 400 ml of the new DSF and two other commercially available DSF (Glucerna^® SR and Novasource^® Diabet) on three occasions separated by 1 week. Venous blood samples were drawn at time 0 and at different times until 120 min. Glucose, insulin and gastrointestinal hormones were determined. Glycaemic and insulinaemic indices and glycaemic load were calculated.

Results

The CHO constituent and the new DSF showed low glycaemic index and glycaemic load. In healthy subjects, insulin and C-peptide release were lower after administration of the CHO constituent as well as after the new DSF (P < 0.001). Ghrelin, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) production were lower after intake of the CHO constituent (P ranging from <0.001 to 0.019) compared with glucose, and GIP was lower after ingestion of the new DSF (P = 0.002) than after the control product. In type 2 diabetic patients, glucose AUC was lower after the administration of the new DSF (P = 0.037) compared with the others.

Conclusions

Our results indicate that this new product could be beneficial for diabetic patients.     

Experience with Crystalline Niacin as the Preferred Drug for Dyslipidemia in a Specialty Clinic

To determine the tolerability and efficacy of crystalline niacin in reaching target lipid goals, we conducted a retrospective review of medical records of 62 patients treated with the agent over 2 years in a lipid clinic at a nonacademic veterans hospital. Most patients received niacin for hypercholesterolemia. Thirty-one patients (50%) stopped therapy due to adverse events, principally, intolerable cutaneous reactions. Twenty-nine withdrew from therapy during the first 6 weeks of treatment. Of those who tolerated niacin, 23 did not achieve target lipid serum concentrations at the maximum tolerated dosage; 8 did achieve target concentrations. Thus crystalline niacin was largely ineffective in treating patients with dyslipidemia.     

Tobacco use among Native Hawaiian middle school students: its prevalence, correlates and implications

Objectives. This study sought to explore whether Native Hawaiian primary ethnic identity is associated with cigarette use among Native Hawaiian middle school students. This study also explored whether social influence, psychosocial and cultural factors are associated with cigarette use in this sample.

Design. The data are from a cross-sectional survey of 1,695 Native Hawaiian middle school students at 22 public and private schools on five islands in Hawaii. A subset of these students from Native Hawaiian serving schools (N = 136) completed additional measures of Hawaiian cultural variables.

Results. Based on univariate analyses, students whose primary ethnic identification was Hawaiian were more likely to have tried smoking (p < 0.001) and to be current smokers (p < 0.05) as compared to those classified as part Hawaiian. However, these findings were no longer significant in multivariate analyses. Social influence variables (i.e. peer and parental smoking) were most influential in explaining both prior and current smoking. Attendance at public school was also an important factor in explaining previous (OR = 2.43; 95% CI = 1.74, 3.38) and current (OR = 7.20; 95% CI = 4.58, 11.32) smoking behavior. Finally, cultural variables such as valuing Hawaiian folklore, customs, activities and lifestyle were largely unassociated with smoking behavior among Native Hawaiian middle school youth.

Conclusions. Additional research is needed to understand what aspects of ethnic identity are associated with smoking behavior among Native Hawaiian youth. The strong influence of peer and parental smoking suggests the need for interventions that support the creation of social environments that discourage tobacco use.     

Adrenal Steroids Modulate the Immune Response during Brucella abortus Infection by a Mechanism That Depends on the Regulation of Cytokine Production

Human brucellosis is a protean disease with a diversity of clinical signs and symptoms resulting from infection with Brucella species. Recent reports suggest a cross-regulation between adrenal steroids (cortisol and dehydroepiandrosterone [DHEA]) and the immune system. Monocytes and macrophages are the main replication niche for Brucella. Therefore, we investigated the role of adrenal hormones on the modulation of the immune response mediated by macrophages in B. abortus infection. Cortisol treatment during B. abortus infection significantly inhibits cytokine, chemokine, and MMP-9 secretion. In contrast, DHEA treatment had no effect. However, DHEA treatment increases the expression of costimulatory molecules (CD40, CD86), the adhesion molecule CD54, and major histocompatibility complex class I (MHC-I) and MHC-II expression on the surface of B. abortus-infected monocytes. It is known that B. abortus infection inhibits MHC-I and MHC-II expression induced by gamma interferon (IFN-γ) treatment. DHEA reverses B. abortus downmodulation of the MHC-I and -II expression induced by IFN-γ. Taken together, our data indicate that DHEA immune intervention may positively affect monocyte activity during B. abortus infection.     

History of prior TB infection and HIV/AIDS risk behaviours among a sample of male inmates in the USA

This study looked at inmates' self-reported data on prior treatment for tuberculosis (TB) and HIV/AIDS risk among a sample of inmates in a medium security prison. Contingency tables were used and risk ratios were computed to provide an estimate of relative risk for inmates with a history of being treated for TB in opposition to inmates without a history of being treated for TB. Findings suggest that inmates who reported being treated for TB were more likely to have had sex with a man while in prison and to report that, while in prison, they had a main sex partner. They were also 1.15 times more likely to have had sex with a person from the transgender community while in prison and 2.53 times more likely to report having been forced to have sex while in prison than those without a past history of being treated for TB. Future studies should attempt to determine the extent to which having an infectious disease such as TB impacts behavioural change with respect to behaviours practised by inmates.     

Adipose stromal vascular fraction improves cardiac function in chronic myocardial infarction through differentiation and paracrine activity

Fresh adipose-derived cells have been shown to be effective in the treatment of acute myocardial infarction (MI), but their role in the chronic setting is unknown. We sought to determine the long-term effect of the adipose derived-stromal vascular fraction (SVF) cell transplantation in a rat model of chronic MI. MI was induced in 82 rats by permanent coronary artery ligation and 5 weeks later rats were allocated to receive an intramyocardial injection of 10(7) GFP-expressing fresh SVF cells or culture media as control. Heart function and tissue metabolism were determined by echocardiography and (18)F-FDG-microPET, respectively, and histological studies were performed for up to 3 months after transplantation. SVF induced a statistically significant long-lasting (3 months) improvement in cardiac function and tissue metabolism that was associated with increased revascularization and positive heart remodeling, with a significantly smaller infarct size, thicker infarct wall, lower scar fibrosis, and lower cardiac hypertrophy. Importantly, injected cells engrafted and were detected in the treated hearts for at least 3 months, directly contributing to the vasculature and myofibroblasts and at negligible levels to cardiomyocytes. Furthermore, SVF release of angiogenic (VEGF and HGF) and proinflammatory (MCP-1) cytokines, as well as TIMP1 and TIMP4, was demonstrated in vitro and in vivo, strongly suggesting that they have a trophic effect. These results show the potential of SVF to contribute to the regeneration of ischemic tissue and to provide a long-term functional benefit in a rat model of chronic MI, by both direct and indirect mechanisms.