Disease Activity Measures

The Multiple Sclerosis Functional Composite (MSEC) was developed by the MS Consortium (Whitaker et al., 1995) for evaluating disabilities ranging from motor function to cognitive changes and to replace the EDSS. The three tools included in the MSEC are a timed 25 foot walk, the 9-hole peg test for hand dexterity and the Paced Auditory Serial Addition Test (PASAT). The MSFC is a quantifiable measure of disabihty but ten years later, it is still infrequently incorporated as a primary outcome measure because of the increased time element necessary to validate the individual tests and the time necessary for their administration. 

Serial MRI documents that clinical MS exacerbations are associated with focal BBB damage. As early as 1965, experimental allergic/autoimmune encephomyelitis (EAE) animal models revealed lymphocyte adherence to post capillary venules and subsequent migration into CNS parenchyma preceding demyelination (Lampert and Carpenter, 1965). Both 

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Change, E., Abrahamowicz, M., Ferland, D., and Fortin, P.R. (2002) Comparison of the Responsiveness of Lupus Disease Activity Measures to Changes in Systematic Lupus Erythematosus Activity Relevant to Patients and Physicians, 7. Clin. Epidemiol. 55,488-497. 

The diagnostic usefulness should be established by appropriate retrospective or prospective studies to see if the test in fact improves the diagnostic accuracy. For inherited enzyme diseases, the measurement of the enzyme activity can be diagnostically specific and highly useful. For otherwise obvious diseases such as metastatic prostatic carcinoma, enzyme tests may be of little value (24). 

The TNF -308 polymorphism may be predictive of an individual patient s response to INF. In one study, 59 RA patients treated with INF after genotyping were classified into homozygotes for the TNF -308A allele (A/A 1.7%), heterozygotes (A/G 22%), and wild-type (G/G 76.3%) carriers of the allele. After 22 weeks of treatment with INF, the disease activity score (DAS a standardized measure of disease activity in RA) was used to assess response to INF. Patients without the A allele (81%) compared to patients with the A allele (42%) had a better response to INF as demonstrated by an improvement in the DAS (p 0.0009). Thus, this study suggested that RA patients who are carriers of the TNF=-30S G allele may have a more favorable response to INF (62). 

The underlying rationale for early application of SBC-5-IMNs in LN is that once renal damage occurs, progressive damage will follow if the disease activity remains high (Systemic Lupus Activity Measure or SLAM score > 4). Indications for therapy with SBC-5-IMNs in DMARD-Refractory LN (DR-LN) include ... 

For cells with /1-galactosidase deficiency (GM1 gangliosidosis or Morquio type as well as I-cell disease), the measured enzyme activity will be significantly lower than the true enzyme activity. In addition, cases of multiple sulfatase deficiency will also show low N-acetylgalactosamine-6-sulfatase activity. Therefore, arylsulfatase A or another sulfatase, as well as /1-galactosidase activities should also be determined in case of suspicious results. To exclude poor sample quality, the determination of a-mannosidase is recommended. 

The authors of the second report commented that activated eosinophils and their cytotoxic products, such as eosinophil catatonic protein, may play a part in the pathogenesis of Churg-Strauss syndrome. Measuring serum concentrations of eosinophil catatonic protein may be useful in monitoring disease activity, since concentrations were increased before treatment and normalized afterwards. 

Based upon these observations and following Phase I safety studies, a Phase II randomized, double-blind, controlled clinical trial was undertaken to treat active ulcerative colitis with escalating doses of ISIS 2302. Based on an intent-to-treat analysis, 59% (13/22) of patients treated daily with 240 mg ISIS 2302 enema over six weeks achieved a positive response, as measured by Disease Activity Index (DAI)... 

The expression of many cytokines has been found to correlate with disease exacerbation and severity. Therefore, the measurement of cytokine concentration may be used as a predictive parameter or disease marker for monitoring disease activity and therapeutic efficacies. 

When tablets or capsules are found in the immediate vicinity of, or in the possession of, an unconscious patient, it is reasonable to assume that a drug overdose has been taken. If the patient responds to supportive treatment and no active measures are contemplated, toxicological analyses are of historical interest only. Conversely, when circumstantial evidence is lacking, a diagnosis of poisoning may be difficult to sustain simply on die basis of clinical examination, since coma induced by drugs is not readily differentiated from that caused by disease processes. The role of the laboratory is important in several types of poisoning cases. 

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