Bright C.J.,University Institute of Health Sciences
Circulation | Year: 2017
BACKGROUND—: Survivors of teenage and young adult (TYA) cancer are at risk of cerebrovascular events, but the magnitude of and extent to which this risk varies by cancer type, decade of diagnosis, age at diagnosis and attained age remains uncertain. This is the largest ever cohort study to evaluate the risks of hospitalisation for a cerebrovascular event among long-term survivors of TYA cancer. METHODS—: The population-based Teenage and Young Adult Cancer Survivor Study (N=178,962) was linked to Hospital Episode Statistics data for England to investigate the risks of hospitalisation for a cerebrovascular event among 5-year survivors of cancer diagnosed when aged 15-39 years. Observed numbers of first hospitalisations for cerebrovascular events were compared to that expected from the general population using standardised hospitalisation ratios (SHR) and absolute excess risks (AER) per 10,000 person-years. Cumulative incidence was calculated with death considered a competing risk. RESULTS—: Overall, 2,782 cancer survivors were hospitalised for a cerebrovascular event—40% higher than expected (SHR=1.4, 95% confidence interval [CI]=1.3-1.4). Survivors of central nervous system (CNS) tumours (SHR=4.6, CI=4.3-5.0), head & neck tumours (SHR=2.6, CI=2.2-3.1) and leukaemia (SHR=2.5, CI=1.9-3.1) were at greatest risk. Males had a significantly higher AER than females (AER=7 versus 3), especially among head & neck tumour survivors (AER=30 versus 11). By age 60, 9%, 6% and 5% of CNS tumour, head & neck tumour, and leukaemia survivors, respectively, had been hospitalised for a cerebrovascular event. Beyond age 60, every year 0.4% of CNS tumour survivors were hospitalised for a cerebral infarction (versus 0.1% expected. Whereas at any age, every year 0.2% of head & neck tumour survivors were hospitalised for a cerebral infarction 7 (versus 0.06% expected). CONCLUSIONS—: Survivors of a CNS tumour, head & neck tumour, and leukaemia are particularly at risk of hospitalisation for a cerebrovascular event. The excess risk of cerebral infarction among CNS tumour survivors increases with attained age. For head & neck tumour survivors this excess risk remains high across all ages. These groups of survivors, and in particular males, should be considered for surveillance of cerebrovascular risk factors and potential pharmacological interventions for cerebral infarction prevention. © 2017 by the American College of Cardiology Foundation and the American Heart Association, Inc.
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.
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.
University Institute of Health Sciences | Date: 2013-07-12
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.
University Institute of Health Sciences | Date: 2013-03-07
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.