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Modifying Effects (modifying + effects)
Selected AbstractsRisk of endometrial cancer in relationship to cigarette smoking: Results from the EPIC studyINTERNATIONAL JOURNAL OF CANCER, Issue 12 2007Mustafa Al-Zoughool Abstract Current epidemiologic evidence indicates that cigarette smoking reduces the risk of endometrial cancer. We examined data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to analyze further aspects of the smoking-endometrial cancer relationship, such as possible modifying effects of menopausal status, HRT use, BMI and parity. In a total of 249,986 women with smoking exposure and menopausal status information, 619 incident endometrial cancer cases were identified during 1.56 million person-years of follow-up. Among postmenopausal women, the hazard ratio (HR) for current smokers versus never smokers was 0.70 (95% CI = 0.53,0.93), while it was 1.75 (95% CI = 1.13,2.70) among premenopausal women at recruitment. After adjustment for risk factors, the HR for postmenopausal women was slightly attenuated to 0.78 (95% CI = 0.59,1.03). No heterogeneity of effect was observed with HRT use or BMI. Among premenopausal women, current smokers of more than 15 cigarettes per day or who smoked for 30 years or more at the time of recruitment had a more than 2-fold increased risk of endometrial cancer compared to never smokers (HR = 2.54; 95% CI = 1.47,4.38 and HR = 2.23; 95% CI = 1.04,4.77, respectively). Past smoking was not associated with endometrial cancer risk, either among pre- or postmenopausal women. In this prospective study, we observed an increased risk of endometrial cancer with cigarette smoking in premenopausal women. The reduction of endometrial cancer risk observed among postmenopausal women does not have direct public health relevance since cigarette smoking is the main known risk factor for cancer. © 2007 Wiley-Liss, Inc. [source] Manganese chelation therapy extends survival in a mouse model of M1000 prion diseaseJOURNAL OF NEUROCHEMISTRY, Issue 2 2010Marcus W. Brazier J. Neurochem. (2010) 114, 440,451. Abstract Previous in vitro and in vivo investigations have suggested manganese (Mn2+) may play a role in pathogenesis through facilitating refolding of the normal cellular form of the prion protein into protease resistant, pathogenic isoforms (PrPSc), as well as the subsequent promotion of higher order aggregation of these abnormal conformers. To further explore the role of Mn2+ in pathogenesis, we undertook a number of studies, including an assessment of the disease modifying effects of chelation therapy in a well-characterized mouse model of prion disease. The di-sodium, calcium derivative of the chelator, cyclohexanediaminetetraacetic acid (Na2CaCDTA), was administered intraperitoneally to mice inoculated intra-cerebrally with either high or low-dose inocula, with treatment beginning early (shortly after inoculation) or late (at the usual mid-survival point of untreated mice). Analyses by inductively coupled plasma-mass spectrometry demonstrated brain Mn2+ levels were selectively reduced by up to 50% in treated mice compared with untreated controls, with copper, iron, zinc and cobalt levels unchanged. In mice administered high-dose inocula, none of the treatment groups displayed an increase in survival although western blot analyses of early intensively treated mice showed reduced brain PrPSc levels; mice infected using low-dose inocula however, showed a significant prolongation of survival (p = 0.002). Although our findings support a role for Mn2+ in prion disease, further studies are required to more precisely delineate the extent of pathogenic involvement. [source] Disease modifying therapy for AD?,JOURNAL OF NEUROCHEMISTRY, Issue 3 2006Todd E. Golde Alzheimer's disease (AD) is the most common form of dementia in industrialized nations. If more effective therapies are not developed that either prevent AD or block progression of the disease in its very early stages, the economic and societal cost of caring for AD patients will be devastating. Only two types of drugs are currently approved for the treatment of AD: inhibitors of acetyl cholinesterase, which symptomatically enhance cognitive state to some degree but are not disease modifying; and the adamantane derivative, memantine. Memantine preferentially blocks excessive NMDA receptor activity without disrupting normal receptor activity and is thought to be a neuroprotective agent that blocks excitotoxicty. Memantine therefore may have a potentially disease modifying effect in multiple neurodegenerative conditions. An improved understanding of the pathogeneses of AD has now led to the identification of numerous therapeutic targets designed to alter amyloid , protein (A,) or tau accumulation. Therapies that alter A, and tau through these various targets are likely to have significant disease modifying effects. Many of these targets have been validated in proof of concept studies in preclinical animal models, and some potentially disease modifying therapies targeting A, or tau are being tested in the clinic. This review will highlight both the promise of and the obstacles to developing such disease modifying AD therapies. [source] The Successful Product Pioneer: Maintaining Commitment while Adapting to ChangeJOURNAL OF SMALL BUSINESS MANAGEMENT, Issue 3 2002Mark Simon Introducing pioneering products is an important entrepreneurial activity and the lifeblood of small businesses, yet previous literature on pioneering and performance in small firms has been inconclusive. Based on data gathered from entrepreneurs in 51 small computer firms, the study found that commitment (entrepreneurial confidence) and adaptability (corporate entrepreneurship and environmental dynamism) were especially beneficial to pioneers. The other three variables (product championing, marketing emphasis, and technological newness) contributed to performance across all new product introductions but did not have modifying effects on pioneering introductions in particular. [source] Victimization, Anger, and Gender: Low Anger and Passive Responses WorkAMERICAN JOURNAL OF ORTHOPSYCHIATRY, Issue 1 2009Kelly M. Champion PhD This study examined the contributions of gender, anger, expectations of positive outcomes, and frequency of victimization by and bullying of peers among school-aged children to predict individual differences in intentions to respond to provocative events with nonassertive behavior. Children between the ages of 9 and 13 (N = 505, 246 female, 259 male) completed the Anger Response Inventory, Child Version (Tangney et al., 1996) and measures of victimization and bullying. Results of regression procedures demonstrated that female gender and low anger predicted ignoring and using distraction. Nonassertive responses, low anger, and low victimization predicted expecting more positive outcomes following provocation. Victimization was unrelated to intentions to use nonassertive responses but bullying negatively predicted walking away and using distraction. No modifying effects for gender, victimization, or bullying were found. [source] Corticosteroids in the treatment of multiple sclerosisACTA NEUROLOGICA SCANDINAVICA, Issue 2009K. M. Myhr Background ,, Multiple sclerosis (MS) is an immune-mediated inflammatory disease of the central nervous system (CNS) that usually is clinically characterized by repeated subacute relapses followed by remissions. Therapeutic strategies include corticosteroid treatment of relapses and immunomodulatory- or immunosuppressive treatment to prevent new relapses and progression of disability. Objectives ,, To review the evidences for the use of corticosteroids in the treatment of relapses in MS as well as its possible disease modifying potential. Materials & Methods ,, Available literature from PubMed search and personal experiences on corticosteroid treatment in multiple sclerosis were reviewed. Results ,, High dose short-term oral or intravenous methylprednisolone for 3-5 days speed up recovery from relapses, but the treatment has no influence on the occurrence of new relapses or long-term disability. There is also some evidence that pulsed treatment with methylprednisolone have beneficial long-term effects in multiple sclerosis. Conclusion ,, Relapses with moderate to serious disability should be treated with high dose intravenous or oral methylprednisolone. More data is needed to determine long-term disease modifying effects of corticosteroids. [source] | ||||||||||