BRMs

All the ealeulations for every analytieal line use its own AC-10 virtual unified sample material eontaining 10% of ehemieal element analyzed. In praetiee, instead of AC-10 speeimen, one ean use eertified sample material named Benehmark Referenee Material (BRM). One must know eomplete ehemieal eontent of BRM. Having measured analytieal line intensity of the speeimen, one ean determine the intensity from AC-10 by eorreetion system. Anyone eertified sample material ean be used as BRM for a few elements. Quantitative eomposition of BRM does not depend on the range of varying ehemieal elements eontent in samples analyzed substantially faeilitating a seleetion and ehange of these BRM. 

BRM and BERM special issues of Fresenius J Anal Chem (available issues BRM-2,1987 BRM-3, 1988 BERM-4, 199° BERM-5, i993i BERM-6, 1995 and BERM-7, r998 for an overview of these symposia see Chapter 8. 

BRM-1 reflected a strong need to initiate and expand RM activities for certifying organic nutrients in foods. 

BRM-2 highlighted the distinction between primary (certified) and secondary (e.g. check samples for proficiency testing) RMs. 

There are a number of trends that will continue to influence future RM activity and a number of areas which are not yet very significant that will become more so. One important source of information on developments in the area of RMs is the series of International Symposia on Biological and Environmental Reference Materials (BERM), organization of which was described in Chapter 8. The Proceedings of these successive BERM Symposia have given a series of detailed snapshots of activity on a 2-3 year cycle over nearly two decades (BRM-i 1985 - BERM-7 99 )- Most of the information and projections in this Chapter are taken from various papers published in these BERM proceedings. 

BRM-i (1985) Proceedings. In Woir WR, ed. Biological Reference Materials Availability, Uses, and Need for Validation of Nutrient Measurement. Wiley, New York. 

Table 54-3 highlights dosing, safety, monitoring, and patient counseling information for the common DMARDs and BRMs. 

TABLE 54-3. FDA-Approved DMARDs and BRMs for Treatment of Rheumatoid Arthritis1 2 7 15 21 42... 

Biologic response modifiers (BRMs) are indicated in patients who have failed an adequate trial of DMARD therapy.1 BRMs may be added to DMARD monotherapy (i.e., methotrexate) or replace ineffective DMARD therapy.22 The decision to select a particular agent generally is based on the prescriber s comfort level with monitoring the safety and efficacy of the medications, the frequency and route of administration, the patient s comfort level or manual dexterity to self-administer subcutaneous injections, the cost, and the availability of insurance coverage.23 In general, BRMs should be avoided in patients with serious infections, demyelinating disorders (e.g., multiple sclerosis or optic neuritis) or heart failure.21... 

The exact role of rituximab in RA is not clearly defined, but it is indicated for patients with moderate to severe RA with a history of inadequate response to DMARDs and other BRMs. Rituximab carries a black-box warning of fatal infusion reactions and severe mucocutaneous reactions even though these events did not occur during the RA clinical trials. The benefits of rituximab must be tempered against the safety concerns reported with use of rituximab in the oncology setting. 

The developments in the treatment of RA are tempered by the lack of evidence describing the long-term safety and efficacy of the BRMs. In addition, the cost associated with the medications can be a deterrent to use. Long-term data are needed to determine if patients receiving BRM therapy early in the course of disease have reduced disease activity, reduced joint deformities and disability, improved quality of life, and continued function as productive members of society. Cost analyses of long-term data may indicate that the increased expenses associated with BRMs are offset by the costs avoided for the treatment of advanced RA. 

The risk of injection inpatients treated with BRMs must be considered when selecting and monitoring therapy.36 Influencing the immune response to reduce symptoms of RA may influence the body s response to pathogens. Of particular concern is the... 

Novotny C, Vyas BRM, Erbanova P, Kubatova A, Sasek V (1997) Folia Microbiol 42 136... 

Natural and Synthetic Biological Response Modifiers (BRMs).159... 

NATURAL AND SYNTHETIC BIOLOGICAL RESPONSE MODIFIERS (BRMs)... 

The use of BRMs to treat human disease has its origins in the use of bacterial toxins to treat cancer by William B. Coley.73 These early studies resulted in the use of microbi-ally-derived substances such as BCG, Picibanil, carbohydrates from plants or fungi such as Krestin and Lentinan, other products such as Biostim and Broncho-Vaxom, as well as thymic extracts (Table 9.4). However, the lot-to-lot variation in the manufacture of these drugs has dampened enthusiasm. Equally, the focus on MOAs in drug development strategies has also dampened developmental efforts. The particulate nature of some BRMs can also result in pulmonary thrombosis and respiratory distress following i.v. injection. However, BRMs are commonly used to treat bladder cancer and derivatives of natural products are routinely used clinically. 

Brm (gxj) matrix with e, column vectors indicating bias positions... 

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