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Chiu D.Y.Y.,University Institute of Health Sciences
Nature Reviews Nephrology | Year: 2015

Patients with chronic kidney disease (CKD) carry a high cardiovascular risk. In this patient group, cardiac structure and function are frequently abnormal and 74% of patients with CKD stage 5 have left ventricular hypertrophy (LVH) at the initiation of renal replacement therapy. Cardiac changes, such as LVH and impaired left ventricular systolic function, have been associated with an unfavourable prognosis. Despite the prevalence of underlying cardiac abnormalities, symptoms may not manifest in many patients. Fortunately, a range of available and emerging cardiac imaging tools may assist with diagnosing and stratifying the risk and severity of heart disease in patients with CKD. Moreover, many of these techniques provide a better understanding of the pathophysiology of cardiac abnormalities in patients with renal disease. Knowledge of the currently available cardiac imaging modalities might help nephrologists to choose the most appropriate investigative tool based on individual patient circumstances. This Review describes established and emerging cardiac imaging modalities in this context, and compares their use in CKD patients with their use in the general population. © 2015 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

Parker B.,University Institute of Health Sciences
Lupus | Year: 2013

Metabolic syndrome (MetS) is a recently defined clustering of cardiovascular risk factors associated with insulin resistance and an increased risk of future type II diabetes mellitus and cardiovascular disease (CVD). Systemic lupus erythematosus (SLE) patients have an increased prevalence of MetS and an increased prevalence of insulin resistance. Chronic inflammation may predispose to these complications in SLE and there is also evidence that corticosteroid therapy also contributes, although this finding has not been as consistent as would be predicted from the known metabolic effects of corticosteroids. MetS may represent a good model in which to begin to understand how SLE drives an increased risk of CVD. For now, the utility of identifying MetS in patients is to identify a subset in which more focused lifestyle interventions should be targeted and in whom medication review and adjustment (especially corticosteroid doses) should be considered to help modify future CVD risk.

Ennis H.,University Institute of Health Sciences
The Cochrane database of systematic reviews | Year: 2014

Calcium channel blockers are the most commonly prescribed drugs for people with primary Raynaud's phenomenon. Primary Raynaud's phenomenon is a common condition characterised by an exaggerated vasospastic response to cold or emotion: classically the digits (fingers and toes) turn white, then blue, then red. To assess the effects of different calcium channel blockers for primary Raynaud's phenomenon as determined by attack rates, severity scores, participant-preference scores and physiological measurements. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched February 2013) and the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 1). In addition the TSC searched clinical trials databases. Randomised controlled trials evaluating the effects of oral calcium channel blockers for the treatment of primary Raynaud's phenomenon. Three review authors independently assessed the trials for inclusion and their quality, and extracted the data. Data extraction included adverse events. We contacted trial authors for missing data. We included seven randomised trials with 296 participants. Although overall all the trials were classed as being at low or unclear risk of bias, the sample size of the included trials was small and there was unclear reporting of outcomes. Four trials examined nifedipine and the remainder nicardipine. Comparisons were with placebo in six trials and with both dazoxiben and placebo in one trial (only the nifedipine versus placebo data were used within this review). Treatment with oral calcium channel blockers was minimally effective in primary Raynaud's phenomenon at decreasing the frequency of attacks (standardised mean difference of 0.23; 95% confidence interval (CI) 0.08 to 0.38, P = 0.003). This translates to 1.72 (95% CI 0.60 to 2.84) fewer attacks per week on calcium channel blockers compared to placebo. One trial provided details on duration of attacks reporting no statistically significant difference between the nicardipine and placebo groups (no P value reported). Only two trials provided any detail of statistical comparisons of (unvalidated) severity scores between treatment groups: one of these trials (60 participants) reported a mean severity score of 1.55 on placebo and 1.36 on nicardipine, difference 0.2 (95% CI of difference 0 to 0.4, no P value reported) and the other trial (three participants only with primary Raynaud's phenomenon) reported a median severity score of 2 on both nicardipine and placebo treatment (P > 0.999). Participant-preference scores were included in four trials, but in only two were results specific to participants with primary Raynaud's phenomenon, and scoring systems differed between trials: scores differed between treatments in only one trial, in which 33% of participants on placebo and 73% on nifedipine reported improvement in symptoms (P < 0.001). Physiological measurements were included as outcome measures in five trials (different methodologies were used in each): in none of these trials were any statistically significant between-treatment group differences found. Treatment with calcium channel blockers appeared to be associated with a number of adverse reactions, including headaches, flushing and oedema (swelling). The randomised controlled trials included in this review provide moderate-quality evidence that oral calcium channel blockers are minimally effective in the treatment of primary Raynaud's phenomenon as measured by the frequency of attacks. However, the results of this review were limited by small sample sizes in the included studies and by variable data quality, particularly with regard to outcome measures.

Lioy P.J.,University Institute of Health Sciences
Environmental Health Perspectives | Year: 2010

Background: The study of human exposure to environmental toxicants has evolved as a scientific field over the past 30 years. Objectives: This review provides a historical perspective on the growth of exposure science as a field, with some emphasis on the results from initial observational studies in obtaining information needed for generating hypotheses on significant human contact with environmental agents, testing the performance of models, and reducing exposures to protect public health. Discussion: Advances in activity pattern and behavioral research that established a suite of variables needed to accurately define contact and factors that influence contact are also discussed. The identification and characterization of these factors have played a pivotal role in the growth of the field and in developing exposure reduction strategies. Answers to two key questions on the relevance and fundamental value of exposure science to the fields of environmental health and risk management are presented as a path forward: a) What does one do with such exposure information? b) What roles does exposure science play in situations beyond observational analyses and interpretation? Conclusions: The discussion identifies the need for more focused use of observational studies of exposure for epidemiologic analyses. Further, the introduction and use of new tools and approaches for hypothesis testing that can improve the use of exposure science in prevention research for risk management is needed to affect the source-to-effect continuum. A major restructuring of the field is not required to achieve innovation. However, additional resources for training and education are required to ensure that the potential for exposure science to play a central role in reducing and preventing excess risk within environmental/occupational health is achieved.

Strasser B.,University Institute of Health Sciences
Annals of the New York Academy of Sciences | Year: 2013

Biological aging is typically associated with a progressive increase in body fat mass and a loss of lean body mass. Owing to the metabolic consequences of reduced muscle mass, it is understood that normal aging and/or decreased physical activity may lead to a higher prevalence of metabolic disorders. Lifestyle modification, specifically changes in diet, physical activity, and exercise, is considered the cornerstone of obesity management. However, for most overweight people it is difficult to lose weight permanently through diet or exercise. Thus, prevention of weight gain is thought to be more effective than weight loss in reducing obesity rates. A key question is whether physical activity can extenuate age-related weight gain and promote metabolic health in adults. Current guidelines suggest that adults should accumulate about 60 minutes of moderate-intensity physical activity daily to prevent unhealthy weight gain. Because evidence suggests that resistance training may promote a negative energy balance and may change body fat distribution, it is possible that an increase in muscle mass after resistance training may be a key mediator leading to better metabolic control. © 2012 New York Academy of Sciences.

University Institute of Health Sciences | Date: 2013-03-11

The present invention includes inhibitors of the amino acid transporter ATB^(0,+) and methods of uses thereof.

University Institute of Health Sciences | Date: 2013-02-07

It has been discovered that STAT5 phosphorylation and CD150 are effective biomarkers for detecting, diagnosing, and monitoring hematological malignancies, including for example lymphomas. Compositions and methods for identifying therapeutic agents for the treatment of hematologic malignancies using p-STAT5, CD150 or both as biomarkers are described.

University Institute of Health Sciences | Date: 2013-01-09

Green tea polyphenol compositions and methods of their use in treating herpes simplex virus (HSV) are provided. Representative green tea polyphenols include, but are not limited to (-)-epigallocatechin-3-gallate as well as green tea polyphenols with one on more ester-linked fatty acids.

The present invention includes inhibitors of the amino acid transporter ATB^(0,+) and methods of uses thereof for the treatment of estrogen receptor-positive breast cancer.

A lentivector has been engineered to express a fusion antigen composed of hepatitis B surface protein (HBsAg) and IgG2a Fc fragment (HBS-Fc-Iv) to increase both the magnitude of CD8 response and to induce effective co-activation of CD4 T cells. Immunization with this HBS-Fc-Iv caused significant regression of established tumors. Immunological analysis revealed that, compared to HBS-Iv without the Fc fragment, immunization with HBS-Fc-Iv markedly increased the number of functional CD8 and CD4 T cells and the level of Th1/Tc1-like cytokines in the tumor, while substantially decreasing the Treg ratio. The favorable immunologic changes in tumor lesions and the improvement of antitumor effects from HBS-Fc-Iv immunization were dependent on the CD4 activation, which was Fc receptor mediated. Adoptive transfer of the CD4 T cells from the HBS-Fc-Iv immunized mice could activate endogenous CD8 T cells in an IFN-dependent manner. Endogenous CD4 T cells can be activated by lentivirus expressing Fc-tagged antigen to provide another layer of help, i.e., creating a Th1/Tc1 like pro-inflammatory milieu within the tumor lesion to help the effector phase of immune responses to enhance the antitumor effect.

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