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Deleterious Outcomes (deleterious + outcome)
Selected AbstractsIncreasing dimethylarginine levels are associated with adverse clinical outcome in severe alcoholic hepatitis,HEPATOLOGY, Issue 1 2007Rajeshwar P. Mookerjee Previous studies suggest reduced hepatic endothelial nitric oxide synthase activity contributes to increased intrahepatic resistance. Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, undergoes hepatic metabolism via dimethylarginine-dimethylamino-hydrolase, and is derived by the action of protein-arginine-methyltransferases. Our study assessed whether ADMA, and its stereo-isomer symmetric dimethylarginine (SDMA), are increased in alcoholic hepatitis patients, and determined any relationship with severity of portal hypertension (hepatic venous pressure gradient measurement) and outcome. Fifty-two patients with decompensated alcoholic cirrhosis were studied, 27 with acute alcoholic hepatitis and cirrhosis, in whom hepatic venous pressure gradient was higher (P = 0.001) than cirrhosis alone, and correlated with ADMA measurement. Plasma ADMA and SDMA were significantly higher in alcoholic hepatitis patients and in nonsurvivors. Dimethylarginine-dimethylamino-hydrolase protein expression was reduced and protein-arginine-methyltransferase-1 increased in alcoholic hepatitis livers. ADMA, SDMA and their combined sum, which we termed a dimethylarginine score, were better predictors of outcome compared with Pugh score, MELD and Maddrey's discriminant-function. Conclusion: Alcoholic hepatitis patients have higher portal pressures associated with increased ADMA, which may result from both decreased breakdown (decreased hepatic dimethylarginine-dimethylamino-hydrolase) and/or increased production. Elevated dimethylarginines may serve as important biological markers of deleterious outcome in alcoholic hepatitis. (HEPATOLOGY 2007;45:62,71.) [source] Deceleration of Regenerative Response Improves the Outcome of Rat with Massive HepatectomyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2010M. Ninomiya Small residual liver volume after massive hepatectomy or partial liver transplantation is a major cause of subsequent liver dysfunction. We hypothesize that the abrupt regenerative response of small remnant liver is responsible for subsequent deleterious outcome. To slow down the regenerative speed, NS-398 (ERK1/2 inhibitor) or PD98059 (selective MEK inhibitor) was administered after 70% or 90% partial hepatectomy (PH). The effects of regenerative speed on liver morphology, portal pressure and survival were assessed. In the 70% PH model, NS-398 treatment suppressed the abrupt replicative response of hepatocytes during the early phase of regeneration, although liver volume on day 7 was not significantly different from that of the control group. Immunohistochemical analysis for CD31 (for sinusoids) and AGp110 (for bile canaliculi) revealed that lobular architectural disturbance was alleviated by NS-398 treatment. In the 90% PH model, administration of NS-398 or PD98059, but not hepatocyte growth factor, significantly enhanced survival. The abrupt regenerative response of small remnant liver is suggested to be responsible for intensive lobular derangement and subsequent liver dysfunction. The suppression of MEK/ERK signaling pathway during the early phase after hepatectomy makes the regenerative response linear, and improves the prognosis for animals bearing a small remnant liver. [source] Effects of long-term administration of N-3 polyunsaturated fatty acids (PUFA) and selective estrogen receptor modulator (SERM) derivatives in ovariectomized (OVX) miceJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2003L. Zeitlin Abstract We studied the beneficial effects of dietary consumption of n-3 polyunsaturated fatty acids (PUFA) and two selective estrogen receptor modulator (SERM) derivatives (SERM-I and SERM-II) and their combined effect on serum lipids, skin dermis and adipose layers, bone marrow adipogenesis, and cytokine secretion in mice. Two different ovariectomized (OVX) models were studied: treatment began immediately post-OVX in one and 3 months post-OVX in the other. Our results showed that n-3 PUFA and both SERMs decreased triglyceride levels in the serum, and that SERMs also decreased serum cholesterol levels while n-3 PUFA had no similar effect. SERMs had no effect on IL-6, IL-1 beta, or IL-10 levels, but they decreased ex vivo tumor necrosis factor (TNF-,). N-3 PUFA decreased secretion of non-induced IL-6 and TNF-, from cultured BMC and IL-1 beta levels in vivo (i.e., in bone marrow plasma), but its main effect was a significant elevation in the secretion of IL-10, a known anti-inflammatory cytokine. OVX-induced B-lymphopoiesis was not affected by LY-139481 (SERM-I) while LY-353381 (SERM-II) exhibited an estrogen-antagonistic effect in sham and OVX mice and elevated the amount of B-cells in bone marrow. Fish oil consumption prevented the elevation in B-lymphopoiesis caused by OVX, but had no curative effect on established augmented B-lymphopoiesis. This activity could be mediated via the elevation of IL-10 which was shown to suppress B-lymphopoiesis. Both SERMs and n-3 PUFA inhibited the increase in adipose tissue thickness caused by OVX in mice. Our results showed that n-3 PUFA, could prevent some of the deleterious outcomes of estrogen deficiency that were not affected by SERMs. We observed no significant beneficial effects of the combined administration of SERM-I, SERM-II, and PUFA on the studied parameters. The exact mechanism by which polyunsaturated fatty acids exert their activities is still not clear, but peroxisome proliferator-activated receptors (PPARs) might be involved in processes which are modulated by n-3 PUFA. J. Cell. Biochem. 90: 347,360, 2003. © 2003 Wiley-Liss, Inc. [source] Comorbidity of mental health and substance misuse problems: a review of workers' reported attitudes and perceptionsJOURNAL OF PSYCHIATRIC & MENTAL HEALTH NURSING, Issue 2 2008M. W. ADAMS rmn bsc (hons) cert. ed (fe) A comorbidity of mental health and substance misuse problems has been associated with deleterious outcomes. In the United Kingdom it has been acknowledged that people with comorbidity have often received poor care, with gaps in service provision suggesting ambivalence towards this issue. Previous reviewing authors have concluded that health professionals hold stereotypical views towards people that misuse substances, but these findings may not be directly comparable to those who work within mental health services. There is however a growing body of evidence concerning this context. The author has reviewed the literature from 1996 to 2006 to ascertain mental health professionals and allied workers attitudes and perceptions towards comorbidity, perceptions on the effectiveness of service systems, and perceptions of personal knowledge and skill in providing effective interventions. The evidence presented mainly pertains to mental health nurses, which reflects their status as the largest discipline within the mental health workforce. Overall attitudes towards comorbidity are mixed, possibly being related to contextual issues of practice and are not necessarily negative. However, there is an almost universal negative perception of deficiencies in service provision and the adequacy of training. Implications for research, development and practice are explored. [source] Fast cars, fast food, and fast fixes: industry responses to current ethical dilemmas for Australian advertisersJOURNAL OF PUBLIC AFFAIRS, Issue 2 2007Sandra C. Jones This paper reviews three ethical dilemmas currently facing advertisers for cars, fast food and pharmaceuticals in the U.S., U.K. and Australia, and discusses Australian industry responses to these dilemmas. In Australia, as in the U.S. and U.K., the main response mechanism for advertisers has been the introduction of self-regulatory codes of practice. It is important to note that in a number of cases there is no conclusive evidence of the argued harm from advertising that is subsequently banned or regulated. A review of the general and trade press, and the records of the Australian Advertising Standards Board, finds that industry responses tend to be based on industry rather than community concerns, with the primary motive being to avoid deleterious outcomes for the industry rather than for society as a whole. Copyright © 2007 John Wiley & Sons, Ltd. [source] Neonatal Alcohol-Induced Region-Dependent Changes in Rat Brain Neurochemistry Measured by High-Resolution Magnetic Resonance SpectroscopyALCOHOLISM, Issue 10 2008Shonagh K. O'Leary-Moore Background:, Maternal drinking during pregnancy can lead to a range of deleterious outcomes in the developing offspring that have been collectively termed fetal alcohol spectrum disorders (FASDs). There is interest and recognized value in using non-invasive neuroimaging techniques such as magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to characterize, respectively, structural and biochemical alterations in individuals with FASDs. To date, however, results with MRS have been inconsistent regarding the degree and/or nature of abnormalities. Methods:, High-resolution magic angle spinning (HR-MAS) proton (1H) MRS is an ex vivo neuroimaging technique that can acquire spectra in small punches of intact tissue, providing clinically relevant neurochemical information about discrete brain regions. In this study, HR-MAS 1H MRS was used to examine regional neurochemistry in frontal cortex, striatum, hippocampus, and cerebellum of young rats previously exposed to ethanol as neonates. Key neurochemicals of interest included N-acetyl-aspartate (NAA), glutamate, GABA, glutamine, creatine, choline and myo -inositol. Results:, Daily neonatal alcohol exposure from postnatal day 4 (PN4) through PN9 significantly reduced levels of NAA and taurine in the cerebellum and striatum, and induced sex-dependent reductions in cerebellar glutamate when measured on PN16. In addition, myo -inositol was significantly increased in cerebellum. The frontal cortex and hippocampus were virtually unaffected by this neonatal alcohol exposure. Conclusion:, Results of this research may have implications for understanding the underlying neurobiology associated with FASDs and aid in testing treatments in the future. Ongoing studies are assessing the developmental persistence of and/or maturational recovery from these changes. [source] Child Reactions to Terrorism: Cautions and Next Steps for ResearchCLINICAL PSYCHOLOGY: SCIENCE AND PRACTICE, Issue 3 2007Alan E. Kazdin Comer and Kendall (2007) have provided an excellent review of what is known about the effects of terrorism on children. They have identified correlates, outcomes, and the many gaps in our current knowledge. The present comments focus on two main issues. First, there are many correlates and risk factors that predict deleterious outcomes following exposure to terrorist acts. Our field occasionally moves quickly to intervention work by altering malleable risk factors as if they played a causal role in the outcome or its amelioration. More work is needed to analyze these correlates and the precise role they play, if any, in the outcome. Second, in a relatively new area of research there are very many gaps in our knowledge. I discuss the need to prioritize and limit the focus of our studies. Priorities highlighted include evaluating the similarities among natural and human-made disasters and evaluating mechanisms of action among correlates that might bear an important role in child outcomes. Apart from the consequences of terrorist acts on children and families, our field must turn to the broader issue. What can our science do alone and in conjunction with other fields to understand and combat the precursors and origins of terrorism? Theory will be wonderful but we will need to have this grounded or tested to ensure we move beyond reasonable ideas or a lavish buffet of untestable interpretations. [source] | ||||||||||