Serum levels of interleukin-6 and tumour-necrosis-factor-alpha are not correlated to disease activity in patients with rheumatoid arthritis after treatment with low-dose methotrexate

Abstract. Cytokines are major mediators of inflammatory responses in rheumatoid arthritis. Some of them have been shown to correlate with the disease activity and thus are proposed to be used for monitoring patients. Therefore the effects of a low-dose therapy with methotrexate on serum concentrations of interleukin-6 (IL-6) and tumour-necrosis-factor-alpha (TNF-α) were examined in eight patients with seropositive rheumatoid arthritis. Serum levels of IL-6 and TNF-α were significantly elevated in patients compared to healthy controls. Before the onset of MTX treatment IL-6 concentrations were correlated to the c-reactive protein ( P < 0·05) but the correlation was abolished after treatment. For TNF-α no correlations neither before nor after treatment were observed. Both cytokines remained substantially elevated after MTX treatment despite a clear reduction in disease activity. Thus we suggest that one of the effects of MTX might be the inhibition of some of the actions of IL-6 and TNF-α.     

HOW INDEPENDENT ARE MULTIPLE ‘INDEPENDENT’ DIAGNOSTIC CLASSIFICATIONS?

Multiple performances of diagnostic tests are commonly employed in clinical practice and epidemiologic research to assess test reliability, to increase sensitivity or specificity, or to correct for misclassification bias. An assumption almost universally made in this context is the assumption of independence of test results conditional on the true value. For dichotomous diagnostic tests, for example, disease present or absent, this assumption is usually not tenable, however, since there is typically a continuum of the traits that underly diagnosis and individuals in the vicinity of the (implicit or explicit) diagnostic cutpoint (such as the threshold of clinical detectibility) are more likely to be misclassified than other individuals. This paper assesses the magnitude of the resulting correlation of diagnostic errors as a function of the distribution of the underlying trait, the magnitude of the measurement error and the diagnostic threshold. It is concluded that errors of diagnostic tests can be strongly correlated even if errors in perception of the underlying trait are independent. It is illustrated by numerical examples that such positive correlation of diagnostic errors can substantially inflate commonly employed indices of reliability, such as the kappa coefficient.     

Specificity of pepsin-catalyzed peptide bond synthesis

The rates of the pepsin-catalyzed synthesis of oligopeptides of the general type A-Phe-Leu-B by the condensation of A-Phe-OH with H-Leu-B have been determined by means of analytical high performance liquid chromatography. Variation of the A group led to large changes in the initial rates of the condensation reaction, and the effect of such changes was found to be similar to that previously found for the secondary specificity of pepsin in the hydrolysis of oligopeptide substrates. Replacement of the Phe and Leu residues of A-Phe-OH or H-Leu-B by other amino acid residues gave relative rates of synthesis in accord with the known primary specificity of the hydrolytic action of pepsin. Partially-acetylated pepsin, which exhibits enhanced hydrolytic activity, also catalyzed the condensation reaction more effectively. The results are discussed in relation to the potential utility and limitations of pepsin as a catalyst in the preparative synthesis of oligopeptides and to the problem of the mechanism of its action.     

Irregular Pacemaker Tachycardia in a Patient with WPW Syndrome and an A-V Universal Pacemaker

We describe a case of an irregular pacemaker circus movement tachycardia in a patient with the Wolff-Parkinson-White syndrome and a normally functioning A-V universal (DDD) pacemaker (Cordis Sequicor 233 D). The mechanism of the artificial circus movement tachycardia, which uses the pacemaker as the anterograde limb and a septally located accessory atrioventricular pathway as the retrograde limb, is discussed.     

High Resolution ECG and Left Ventricular Volume After Acute Myocardial Infarction

The presence of ventricular late potentials (LPs) early after acute myocardial infarction (AMI) was recently reported to correlate with left ventricular dilatation subsequent to AMI. We assessed prospectively the relationship between LP (time domain) in the late phase of AMI and left ventricular end-diastolic volume (EDV) measured by equilibrium radionuclide angiocardiography 4 weeks and 12 months after AMI. In 80 consecutive patients 4 weeks and 12 months after thrombolytic therapy for AMI, LP and EDV were deter mined (EDV1, EDV2). There was no significant correlation between QRS duration (r = 0.18), RMS40 (r = 0.08), or LAS40 (r = 0.1) and EDV1 or EDV2 in patients with or without LP at baseline. In both groups (patients with [n = 15] and without LP [n = 65]), EDVl and EDV2 were comparable (128 ± 32 mL vs 126 ± 35 mL; 114 ± 40 mL vs 117 ± 36 mL; P = NS). In addition, there was no significant difference between EDVl and EDV2 in patients who developed new LP (n = 6) or lost LP (n = 9) 12 months after AMI. In contrast to LP in the very early phase after AMI, there seems to be no significant correlation between the high resolution ECG in the late phase after thrombolytic therapy for AMI and left ventricular EDV.