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Maximal Benefit (maximal + benefit)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

Prospects for therapeutic vaccination with glatiramer acetate for neurodegenerative diseases such as Alzheimer's disease

DRUG DEVELOPMENT RESEARCH, Issue 2 2002
Michal Schwartz
Abstract Neurodegenerative diseases, whatever their primary causes, are characterized by certain common features, one of which is their self-perpetuating nature. The ongoing progression of the disorder is due to the effects of destructive self-compounds, whose presence in the tissues is an outcome of the early phase of the disease and which gradually destroy remaining functional neurons. Studies in our laboratory have led to the recent formulation of a novel concept of protective autoimmunity as the body's mechanism of defense against these destructive self-compounds. This autoimmune response to central nervous system (CNS) insults is mediated by T-cells and presumably operates by activating and regulating local microglia and infiltrating macrophages (inflammatory response) to carry out their function of clearing destructive material from the tissue at risk. We suggest that a well-controlled autoimmunity counteracts and overcomes the destructive effects of the potentially harmful self-compounds, at the cost of some loss of tissue. An additional risk to the individual is the induction of an autoimmune disease, which is likely to occur if the autoimmune response is malfunctioning. An optimal balance of the various factors will lead to an outcome of maximal benefit at minimal cost to the tissue. A procedure for safely boosting the autoimmune response, by vaccination with a weak self-crossreactive antigen such as glatiramer acetate (also known as Cop-1) was found to protect rats from glutamate toxicity, a major mediator of the spread of damage and a well-known causative factor in neurodegenerative disorders. Cop-1, when administered according to a different regimen, is an FDA-approved drug for the treatment of multiple sclerosis. Different formulations of the same drug can therefore be used to treat two extreme manifestations of chronic degenerative diseases of the CNS. Drug Dev. Res. 56:143,149, 2002. © 2002 Wiley-Liss, Inc. [source]

Prudence and Constitutional Rights

AMERICAN JOURNAL OF ECONOMICS AND SOCIOLOGY, Issue 1 2004
Edward F. McClennen
ABSTRACT. In The Calculus of Consent, Buchanan and Tullock argue for institutional safeguards to ensure maximal benefit for all members of a community against the potential tyranny of the majority. I extend this idea by introducing prudential concerns and argue that they ought to be factored into the decision making that constructs such safeguards. Specifically, I see the safeguarding of prudential concerns for all members of society as a matter that should be secured from the random fate of the political process by constitutional provisions. [source]

Comments on McClennen's "Prudence and Constitutional Rights"

AMERICAN JOURNAL OF ECONOMICS AND SOCIOLOGY, Issue 1 2004
Or How Do You Turn Words Into Action?
ABSTRACT. In The Calculus of Consent, Buchanan and Tullock argue, among other things, that institutional safeguards are required to ensure maximal benefit for all members of a community against the potential tyranny of the majority. McClennen extends this idea by introducing prudential concerns and argues that they ought to be factored into the decision making that constructs such safeguards. Specifically, McClennen sees the safeguarding of prudential concerns for all members of society as a matter of distribution that should be secured from the random fate of the political process through constitutional means. His method for ensuring the constitutional mandate is to place the responsibility for achieving this result in the hands of the judiciary. I argue that there are two problems with his solution: (1) it is ahistorical; and (2) it assumes the judiciary is without politics. [source]

Strategy in clinical practice for classification of unselected colorectal tumours based on mismatch repair deficiency

COLORECTAL DISEASE, Issue 5 2008
L. H. Jensen
Abstract Objective, Deficiency of DNA mismatch repair (MMR) causes microsatellite instability (MSI) in a subset of colorectal cancers. Patients with these tumours have a better prognosis and may have an altered response to chemotherapy. Some of the tumours are caused by hereditary mutations (hereditary nonpolyposis colon cancer or Lynch syndrome), but most are epigenetic changes of sporadic origin. The aim of this study was to define a robust and inexpensive strategy for such classification in clinical practice. Method, Tumours and blood samples from 262 successive patients with colorectal adenocarcinomas were collected. Expression of the MMR proteins MLH1, MSH2, and MSH6 by immunohistochemistry (IHC) was compared with MSI DNA analysis. Methylation analysis of MLH1 and mutation analysis for BRAF V600E were compared in samples with MSI and/or lack of MLH1 expression to determine if the tumour was likely to be sporadic. Results, Thirty-nine (14.9%) of the tumours showed MMR deficiency by IHC or by microsatellite analysis. Sporadic inactivation by methylation of MLH1 promoter was found in 35 patients whereby the BRAF activating V600E mutation, indicating sporadic origin, was found in 32 tumours. On the basis of molecular characteristics we found 223 patients with intact MMR, 35 patients with sporadic MMR deficiency, and four patients who were likely to have hereditary MMR deficiency. Conclusion, To obtain the maximal benefit for patients and clinicians, MMR testing should be supplemented with MLH1 methylation or BRAF mutation analysis to distinguish sporadic patients from likely hereditary ones. MMR deficient patients with sporadic disease can be reassured of the better prognosis and the likely hereditary cases should receive genetic counselling. [source]