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Disease Modification (disease + modification)
Selected AbstractsThe Treatment of Cognitive Impairment Associated with Parkinson's DiseaseBRAIN PATHOLOGY, Issue 3 2010David J. Burn FRCP Abstract Cognitive impairment and dementia associated with Parkinson's disease (PD) are common and often have devastating effects upon the patient and their family. Early cognitive impairment in PD is frequent, and the functional impact may be underestimated. Optimal management will rely upon better identification of the predominant symptoms and greater knowledge of their pathophysiological basis. The management of dementia in PD (PD-D) also has to consider the significant neuropsychiatric burden that frequently accompanies the cognitive decline, as well as fluctuations in attention. Atypical anti-psychotics have a limited role at present in treating PD-D, although new drugs are under development. The mainstay of drug management for people with PD-D is cholinesterase inhibitors, although recent trials have suggested that the N-methyl-D aspartate antagonist memantine may also have some benefit. Disease modification remains the ultimate goal for preventing the inexorable decline in PD-D, although effective interventions are still some way off. Limited benefit may, however, be possible through exercise programmes and so-called "medical foods", although randomised trials are required to confirm largely anecdotal observations. [source] Differences in End-of-Life Preferences Between Congestive Heart Failure and Dementia in a Medical House Calls ProgramJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 5 2004Ziad R. Haydar MD Objectives: To compare end-of-life preferences in elderly individuals with dementia and congestive heart failure (CHF). Design: Retrospective case-control study. Setting: Geriatrician-led interdisciplinary house-call program using an electronic medical record. Participants: Homebound individuals who died while under the care of the house-call program from October 1996 to April 2001. Measurements: Medical records review for demographics, functional status, advance medical planning, hospice use, and place of death. Results: Of 172 patients who died in the program, 29 had CHF, 79 had dementia, 34 had both, and 30 had neither. Patients with CHF were younger (82.6 vs 87.0, P=.011) and less functionally dependent (activities of daily living score 9.1 vs 11.5, P=.001). Time from enrollment to death was not significantly different (mean±standard deviation=444±375 days for CHF vs 325±330 days for dementia, P=.113). A do-not-resuscitate (DNR) directive was given in 62% of patients with CHF and 91% with dementia (P<.001). Advance medical planning discussions were not significantly different (2.10 in CHF vs 1.65 in dementia, P=.100). More patients with CHF participated in their advance medical planning than those with dementia (86% vs 17%, P<.001). Hospice was used in 24% of CHF and 61% of dementia cases (P<.001). Finally, 45% of patients with CHF and 18% of patients with dementia died in the acute hospital (P=.006). Multivariate analysis showed that the fact that more patients with CHF were involved in their medical planning was not significant in predicting end-of-life preferences. Alternatively, Caucasian ethnicity was an independent predictor of having a documented DNR and death outside of the acute hospital. Conclusion: In the months before death, patients with CHF were more likely to have care plans directed at disease modification and treatment, whereas dementia patients were more likely to have care plans that focused on symptom relief and anticipation of dying. Several factors may contribute to this difference. [source] Targeting epileptogenesis-associated induction of neurogenesis by enzymatic depolysialylation of NCAM counteracts spatial learning dysfunction but fails to impact epilepsy developmentJOURNAL OF NEUROCHEMISTRY, Issue 2 2008Anton Pekcec Abstract Polysialylation is a post-translational modification of the neural cell adhesion molecule (NCAM), which in the adult brain promotes structural changes in regions of neurogenesis and neuroplasticity. Because a variety of plastic changes including neurogenesis have been suggested to be functionally involved in the pathophysiology of epilepsies, it is of specific interest to define the impact of the polysialic acid (PSA)-NCAM system on development of this disease and associated comorbidities. Therefore, we studied the impact of transient enzymatic depolysialylation of NCAM on the pathophysiology in an electrically induced rat post-status epilepticus (SE) model. Loss of PSA counteracted the SE-induced increase in neurogenesis in a significant manner. This effect of endoneuraminidase (endoN) treatment on hippocampal neurogenesis did not impact the subsequent development of spontaneous seizures. In contrast, transient lack of PSA during SE and in the early phase of epileptogenesis exhibited a cognition sparing effect as revealed in the Morris water maze paradigm. In conclusion, our data do not support a central role of neurogenesis in the development of a hyperexcitable epileptic network. However, in view of the cognition-sparing effect, the transient modulation of the PSA-NCAM system seems to allow beneficial long-term disease modification, which might be mediated by the partial normalization of neurogenesis. [source] MMP-mediated collagen breakdown induced by activated protein C in equine cartilage is reduced by corticosteroidsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2010Elaine R. Garvican Abstract The plasma serine protease activated protein C (APC) is synthesized by human chondrocytes at sites of pathological cartilage fibrillation. APC levels are increased in osteoarthritis (OA) synovial fluid, and in vitro APC has been shown to synergize with interleukin-1, (IL-1) to promote degradation from ovine cartilage. A model of equine cartilage degradation was established and used to explore corticosteroid activities. Intraarticular corticosteroids are a commonly prescribed treatment for joint disease, however their role in disease modification remains unclear. APC synergized with IL-1 or tumor necrosis factor-, (TNF,), promoting significant collagen degradation from equine cartilage explants within 4 days, but did not augment glycoaminoglycan (GAG) release. APC activated pro-matrix metalloproteinases (MMP)-2 but not pro-MMP-9, as assessed by gelatin zymography. APC did not directly activate pro-MMP-13. Dexamethasone, triamcinolone, and methylprednisolone acetate (MPA) were evaluated at concentrations between 10, 5M and 10,10M. High concentrations significantly increased GAG release from IL-1+APC,treated explants. With the exception of MPA at 10,10M, all concentrations of corticosteroids caused significant decreases in IL-1+APC-driven hydroxyproline loss. Treatment with corticosteroids suppressed expression of MMP-1, -3, and -13 mRNA. The collagenolysis associated with IL-1+APC synergy, and the inhibition of this effect by corticosteroids may involve gelatinase activation and downregulation of MMP expression, respectively. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:370,378, 2010 [source] Defining disease-modifying therapies for PD,A road map for moving forward,MOVEMENT DISORDERS, Issue 12 2010C. Warren Olanow MD Abstract A disease-modifying therapy that slows or stops disease progression is one of the major unmet needs in the management of Parkinson's disease. To date, no therapy has been approved for disease modification despite promising laboratory data and positive results in clinical trials. This is because confounding symptomatic or pharmacologic effects cannot be excluded. The delayed start study provides an opportunity to define therapies that provide benefit that cannot be explained by an early symptomatic effect alone. However, this trial design does not necessarily provide a meaningful measure of the effect of the intervention on cumulative disability. In contrast, the long-term simple study provides a measure of the effect of the drug on cumulative disability but does not address mechanism of action. Together these two trials provide a road map for defining a disease modifying drug and determining the long term cumulative effect of the drug on the disease. © 2010 Movement Disorder Society [source] | |||||||||||||