Early treatment of multiple sclerosis to prevent neurologic damage
ABSTRACT Multiple sclerosis (MS) involves ongoing accumulating CNS damage. Precisely which environmental factors trigger onset and progression of the disease are not known. However, clinical trials indicate benefits from early use of disease-modifying therapies (DMTs). All the completed clinically isolated syndrome trials (CHAMPS, ETOMS, BENEFIT, PRECISE) reported significant suppression of subsequent relapse and MRI lesion formation from use of DMT at the first relapse. This article reviews data on early treatment. Such an approach requires the ability to recognize clinically isolated syndrome features that indicate a diagnosis of MS.
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ABSTRACT: Multiple sclerosis is the most common non-traumatic neurodegenerative disease in adults. Most of the patients present with both physical and mental deficits which reflect the dissemination of the lesions in the central nervous system, produced by the inflammatory process. The incomplete recovery after relapses, the accumulation of new deficits and the progressive nature of the condition interfere with daily activities of individuals and have a negative impact on their well-being. Indeed, studies show that quality of life measurements are constantly lower in patients with multiple sclerosis. Estimation of health-related quality of life is being increasingly recognized as necessary when analysing the effectiveness of treatment modalities and for the follow up of patients with chronic diseases such as multiple sclerosis. Current immunomodulatory interventions that are shown to reduce the frequency of relapses and delay disease progression might also have a positive effect on quality of life measurements. Additive pharmacological agents that target cognitive impairments and common symptoms such as depression, fatigue and pain, along with life-style modifications and rehabilitation programmes are also important for the appropriate management that aims to improve quality of life.International Review of Psychiatry 01/2010; 22(1):67-82. DOI:10.3109/09540261003589521 · 1.80 Impact Factor
Article: The biology of E7[Show abstract] [Hide abstract]
ABSTRACT: Papillomaviruses, which produce either benign or malignant lesions have to replicate in cells that are programmed to terminally differentiate. Therefore, both groups of viruses have to stimulate cells into S-phase for successful replication. HPV-16 E7 stimulates G1 to S-phase progression by a series of interactions, which hinge on the ability of the protein to modulate cellular transcription, usually of genes that are essential for successful passage through G1 and into S-phase, such as cdc25A and cyclin E/cdk2. In addition, E7 can regulate the activity of kinase inhibitors such as p21CIP, so that they are shunted to the cytoplasm and away from the site of action of cyclin kinases in the nucleus. The mechanism involves the activity of the Akt family of kinases, but how this is regulated by E7 is unclear, although it may involve genes modulated by Rb. While the interaction with Rb is important, there are Rb-independent interactions, which are also important for E7 biology and it will be interesting in the coming years to determine the nature of these proteins and their function.While progress has been made in delineating the pathways used by malignant viruses to stimulate the cell cycle, the big unknown is how HPV-6 and other benign viruses achieve the same feat. So far, nearly all the biology observed with HPV-16 E7 is not observed with HPV-6 E7, and so it is difficult to see how these latter viruses could stimulate G1 to S-phase by the same pathways. The next few years will I hope see some advances in understanding the biology of the low risk types.Perspectives in Medical Virology 01/2002; DOI:10.1016/S0168-7069(02)08018-7
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ABSTRACT: The management paradigm for multiple sclerosis (MS) continues to evolve and is shifting toward earlier diagnosis, differentiation of patients with varying clinical prognoses, and earlier initiation of treatment in selected individuals. Based on surveys conducted at the 2008 annual conference of the Academy of Managed Care Pharmacy (AMCP) and at regional meetings held in 2009, several topics were identified for which pharmacists indicated a need for new and updated information. To review (a) recent insights into the pathophysiology underlying MS, (b) the improvements in identification of patients with a clinically isolated syndrome (CIS) who will progress to clinically definite MS (CDMS), (c) the current role of magnetic resonance imaging (MRI) and other technologies in the diagnosis and ongoing management of MS, (d) the optimal time to initiate treatment in patients with CIS or MS, and (e) the potential utility of new and emerging therapies in MS management. The medical education company PRIME conducted an educational needs assessment regarding knowledge of recent developments and future directions in MS management at a symposium held at the Academy of Managed Care Pharmacy Educational Conference in Kansas City, Missouri, on October 17, 2008. This was augmented by an ongoing educational needs assessment initiative that involved a national series of regional dinner meetings for managed care pharmacists on the topic of MS in the first 3 quarters of 2009. Collectively, these needs assessments were designed to determine educational gaps that existed after participants attended the symposia on MS, in an effort to plan a follow-up enduring educational activity that addressed those gaps. Measures of learners' post-program intent were collected, as well as specific topic areas recommended for a follow-up activity. Advances have been made in the understanding of CIS subtypes and refinement of MS diagnostic criteria. Early initiation of treatment in patients with a CIS has been shown to prolong the time to progression to CDMS, delay the development of disability, and may also decrease longterm health care costs. In addition, a number of novel therapies for patients with MS are in late stages of clinical development, including several oral medications that are of particular interest to managed care pharmacists. These will provide potentially attractive treatment alternatives for patients with MS, who currently must choose from a selection of injectable drugs.Journal of managed care pharmacy: JMCP 01/2009; 15(9 Suppl A):S2-15; quiz S16-7. · 2.68 Impact Factor